For the final day, I continued with advanced carbohydrate counting/insulin dose adjustment based on intake because this was the method I identified with the most. I believe that this would be the most accurate way to manage blood glucose levels whether you have type 1 or type 2 diabetes, assuming the patient has the motivation and understanding to do it.
This week has been fun, and educational. Compared to the week I spent on the renal (pre-dialysis) diet in my undergrad MNT class, this was a piece of cake (no pun intended). Here’s what I got out of it (in no particular order of importance):
1. I am happy to say I have gotten over my fear of needles. I can’t even watch when someone else gives me a shot. Orientation was the first time I was able to actually stick myself with a needle. In the past, I had to have someone else do it. Now, after sticking myself 3 times a day for 7 days, I’m pretty numb to it.
2. I would make a great diabetic patient. My typical meal pattern is already pretty evenly distributed with carbohydrate. I’m a huge perfectionist and am very organized, and have a good memory for things like checking blood sugar. I almost always have my meals planned out, at least in my head, for the whole day. I have been known to look up the nutrition information of restaurant menus before I go there, so I can decide what I’m getting before I arrive. I realize that it is extremely unlikely that my patients will come equipped with all, if any, of these attributes.
3. Don’t freeze the other half of the large/medium banana for later. Share it with a friend, or just use the whole darn thing and adjust for it. Icky texture change is not worth it!
4. Hooray for wine, a great low carb drink choice!
5. Despite my desire to follow the meal plan precisely, something always came up that caused me to change it in some way or another. That’s life – you just have to be ready to deal with it. I will remember this when working with patients, and will focus on education so that they can adjust for changes in their plan.
6. I love advanced carbohydrate counting! I know I am going to want everyone to get there, but will have to recognize when people are and aren’t ready for this method. For some, the plate method (although I practically loathed it) will be the most appropriate thing to teach.
7. I believe the hardest part about being diagnosed with diabetes would be the perceived loss of freedom and ability to be spontaneous. You can’t just eat or drink whatever or whenever you want, and you always have to carry your supplies with you. You have to be aware of what you’re eating, how much, and how you’re feeling between meals. You have to be prepared and know what to do in case your blood sugar gets to low. I have a feeling that many people probably go through some period of denial/anger after being diagnosed. It will be important to recognize this in patients and only give them the information they are ready to hear so as not to overwhelm them even more.
Sunday, November 14, 2010
Diabetes - Day 6
Today was a very different day for me, food-wise. I was at work and did not eat lunch until after 3pm, so I didn’t need my afternoon snack. We also decided to go out to dinner tonight, at a restaurant I’ve only eaten at a few times. Needless to say, this required some estimation once the food was in front of me. I ordered the cabbage rolls, which were stuffed with beef, rice, and herbs. Using the exchange system, I estimated the carbohydrate content the best I could. When I got home, I looked up the actual information and saw that I was quite close! The restaurant we ate at did not have nutrition information on their website, and they are not a large chain so probably aren’t required to have it available. I used the information for a similar recipe to decide whether my estimation was correct.
I also had two glasses of wine with dinner, which is really a good choice if you have diabetes. A 5 ounce glass of most types of wine (Pinot Noir was my choice) only has about 3 grams of carbohydrate, whereas a 12 ounce glass of beer has 10 grams. I won’t even get into how high some of those mixed drinks/fruity martinis could probably get.
The fact that I’m playing a person with type 1 diabetes, and the fact that I was drinking, made me think of an ex-boyfriend of mine (this was over 10 years ago) who was in that situation. I was only 19 at the time and didn’t really understand anything about his condition, except he was always saying that he had to eat (it was not optional) and of course, had to give himself shots of insulin. On his 21st birthday, he had a huge party at his house and was drinking hard liquor in excess. Early the next morning, I was sitting next to him and he starting having a seizure and passed out. It was terrifying! I screamed for his parents and we called 911. The paramedics arrived and gave him a shot (glucose?) and he woke up and was fine.
For a long time, I thought that this directly resulted from his drinking alcohol, but I now know it was a severe case of hypoglycemia. He hadn’t eaten, and was only drinking hard liquor, which contains no carbohydrate. Maybe if he would have thrown in a beer or two, or had something to eat at some point, the situation would not have escalated the way it did. All I know is that if I hadn’t been sitting right there, it’s possible that no one would have found him for hours since everyone else in the house was asleep. Even then, things were not going great between us and we broke up shortly thereafter, but I still believe that I was meant to be with him long enough to help in that situation.
Today I learned that the greatest challenge of carbohydrate counting/insulin dose adjustment would likely be going out to dinner at an unfamiliar restaurant. You would need excellent skills of estimation, or would need to know what you were going to order before arriving at the restaurant. These days, as many people have access to the internet via their cell phone (I am not one of those people), I could see this being less of a challenge because you could probably locate the needed information very quickly. Also, if the evening was going to involve alcohol, it would be important to be aware of the carbohydrate content (or lack thereof) of the drinks you would likely consume. This would be especially relevant for people with type 1 diabetes, as it is typically diagnosed during the teen years, prior to gaining any kind of experience with alcohol. As with my ex-boyfriend, unawareness of these facts, coupled with the effect that alcohol consumption has on reasoning, situations like this can turn dangerous very easily. I will definitely keep this in mind in the future if and when I work with teenage/young adult patients with type 1 diabetes.
I also had two glasses of wine with dinner, which is really a good choice if you have diabetes. A 5 ounce glass of most types of wine (Pinot Noir was my choice) only has about 3 grams of carbohydrate, whereas a 12 ounce glass of beer has 10 grams. I won’t even get into how high some of those mixed drinks/fruity martinis could probably get.
The fact that I’m playing a person with type 1 diabetes, and the fact that I was drinking, made me think of an ex-boyfriend of mine (this was over 10 years ago) who was in that situation. I was only 19 at the time and didn’t really understand anything about his condition, except he was always saying that he had to eat (it was not optional) and of course, had to give himself shots of insulin. On his 21st birthday, he had a huge party at his house and was drinking hard liquor in excess. Early the next morning, I was sitting next to him and he starting having a seizure and passed out. It was terrifying! I screamed for his parents and we called 911. The paramedics arrived and gave him a shot (glucose?) and he woke up and was fine.
For a long time, I thought that this directly resulted from his drinking alcohol, but I now know it was a severe case of hypoglycemia. He hadn’t eaten, and was only drinking hard liquor, which contains no carbohydrate. Maybe if he would have thrown in a beer or two, or had something to eat at some point, the situation would not have escalated the way it did. All I know is that if I hadn’t been sitting right there, it’s possible that no one would have found him for hours since everyone else in the house was asleep. Even then, things were not going great between us and we broke up shortly thereafter, but I still believe that I was meant to be with him long enough to help in that situation.
Today I learned that the greatest challenge of carbohydrate counting/insulin dose adjustment would likely be going out to dinner at an unfamiliar restaurant. You would need excellent skills of estimation, or would need to know what you were going to order before arriving at the restaurant. These days, as many people have access to the internet via their cell phone (I am not one of those people), I could see this being less of a challenge because you could probably locate the needed information very quickly. Also, if the evening was going to involve alcohol, it would be important to be aware of the carbohydrate content (or lack thereof) of the drinks you would likely consume. This would be especially relevant for people with type 1 diabetes, as it is typically diagnosed during the teen years, prior to gaining any kind of experience with alcohol. As with my ex-boyfriend, unawareness of these facts, coupled with the effect that alcohol consumption has on reasoning, situations like this can turn dangerous very easily. I will definitely keep this in mind in the future if and when I work with teenage/young adult patients with type 1 diabetes.
Diabetes - Day 5
Today I played the role of a person with type 1 diabetes, who must administer the appropriate amount of insulin in order to achieve blood glucose control. I felt that the best meal plan to use for this situation was advanced carbohydrate counting. This is the most precise method for meal planning, and I knew before I even tried it that it would be my favorite.
I don’t like estimations – especially because, as previously mentioned, I noticed that many of the foods I ate did not match up to the estimations used in the exchange system. They were fairly close, but I am concerned that the little differences could add up to a lot over a whole day. If I am going to base my insulin dosage off the foods that I’m eating at each meal, I would want it to be as exact as possible. That’s probably why the carbohydrate counting method is taught to patients who are diagnosed with type 1 diabetes – at least that has been my observation so far at my hospital. We print the exact carbohydrate content of each menu item on the pediatric menu so that patients (and their parents) can use this method while they are inpatients. I also see a lot about carbohydrate counting education in the dietitian’s notes.
So, needless to say, today was my favorite day so far. I liked the freedom of eating what I wanted (within reason) for my meals, and I loved the accuracy that this method provides. I believe this would truly be the best way to manage blood glucose levels, but I understand that it might take someone awhile to arrive at a level of readiness for this – especially if they were not used to reading nutrition information. They would also have to be at the appropriate level of literacy, as well as motivation, for this to be appropriate. But for me (the self-proclaimed perfectionist) as the patient this week – I am in heaven!
I don’t like estimations – especially because, as previously mentioned, I noticed that many of the foods I ate did not match up to the estimations used in the exchange system. They were fairly close, but I am concerned that the little differences could add up to a lot over a whole day. If I am going to base my insulin dosage off the foods that I’m eating at each meal, I would want it to be as exact as possible. That’s probably why the carbohydrate counting method is taught to patients who are diagnosed with type 1 diabetes – at least that has been my observation so far at my hospital. We print the exact carbohydrate content of each menu item on the pediatric menu so that patients (and their parents) can use this method while they are inpatients. I also see a lot about carbohydrate counting education in the dietitian’s notes.
So, needless to say, today was my favorite day so far. I liked the freedom of eating what I wanted (within reason) for my meals, and I loved the accuracy that this method provides. I believe this would truly be the best way to manage blood glucose levels, but I understand that it might take someone awhile to arrive at a level of readiness for this – especially if they were not used to reading nutrition information. They would also have to be at the appropriate level of literacy, as well as motivation, for this to be appropriate. But for me (the self-proclaimed perfectionist) as the patient this week – I am in heaven!
Thursday, November 11, 2010
Diabetes - Day 4
Today, I took advantage of the “exchange” property of the exchange system and switched up my meals a little. I woke up really wanting French toast, so I had two slices of that instead of a cup of cereal. I still had the banana, and instead of milk I had yogurt. The almonds that would have gone in my cereal were switched out for Smart Balance on the toast. I used about a tablespoon on lite syrup…I don’t like much, anyway. Normally, I would have put powdered sugar on top, but I didn’t really miss it.
I like the idea of the exchange list, because it really teaches people about the carbohydrate content of foods and the fact that carbohydrate can have the same affect on blood sugar regardless of its source. Working at the hospital, I find that many patients are surprised that fruit and milk have carbohydrates. They usually think carbs are only found in bread and sweets. “Sugar free” foods are also very misleading. We have “sugar free” cake on our menu, and it still counts as two carbohydrate exchanges…the same as the “non sugar free” cake. What’s the point?
The only problem I have with the exchange system is that it is merely an estimate. This is helpful, but I found that some of the foods I consumed were actually quite off from the carbohydrate content supposed by the exchange system. For example, two slices of the bread I buy has only 22 grams of carbohydrate, rather than 30. It’s true, it is a little under an ounce per slice, and I seek out bread that does not have large amounts of added sugar in the ingredients-but the point is that most people would not scour the label for this information.
On that note, I’m really looking forward to the next 3 days when I will be using advanced carbohydrate counting for my meal planning. That means I’ll be using the actual food labels to determine the carbohydrate content of the foods I’m eating.
Wednesday, November 10, 2010
Diabetes - Day 3
Today I moved on to the exchange system for meal planning. I like this method much better, because it is more flexible and I don't feel like my plate has to look a certain way. On that note, I put everything in a BOWL this morning for breakfast. I had my favorite - oats made with skim milk, banana, and walnuts. I used the other half of the banana from the other day, which I put in the freezer (I am waaaaay to cheap to throw that away!). Well, I found out the hard way that previously frozen bananas are not so good. I sliced it up straight from the freezer and put it in the hot oatmeal to thaw it. Yuck, what a mushy mess it became. I've put "on the edge" bananas in the freezer before to use for banana bread later, but never tried eating one. Well, I won't be doing that again. I'd rather adjust my exchanges so I can put the whole thing in my cereal.
I developed a meal pattern, based on my usual intake, to use for my exchange system meal plans. I more or less followed the plan today - except I didn't put cheese on my sandwich at lunch (hadn't been to the store yet), and didn't end up having a piece of bread with dinner. It just looked like I already had way too much food on my plate.
I haven't commented on checking my blood sugar yet. I have remembered to do it three times per day, and have chosen sporadic times in order to get a wider range of values. This morning my blood sugar was 74, which is in the normal range but somewhat low compared to the rest of my values. I wonder if it was due to my using the plate method for my meals. I definitely felt like I was eating less than normal, and certainly taking in much less carbohydrate than I'm used to.
Today felt a lot more "normal" for me, as the exchange system allows you to individualize your pattern, and switch things out. For example, I could easily trade out a starch serving for a milk or a fruit, since they all have about the same carbohydrate content. The goal is to keep carbohydrate intake fairly even throughout the day, at meals and snacks. This was relatively easy since I was already doing this fairly well. The one thing I have to keep reminding myself of is that potatoes and potato chips count as a starch, not a vegetable, because their carbohydrate content is higher. I'm used to counting them as a vegetable when I plan my meals according to the MyPyramid guidelines.
I developed a meal pattern, based on my usual intake, to use for my exchange system meal plans. I more or less followed the plan today - except I didn't put cheese on my sandwich at lunch (hadn't been to the store yet), and didn't end up having a piece of bread with dinner. It just looked like I already had way too much food on my plate.
I haven't commented on checking my blood sugar yet. I have remembered to do it three times per day, and have chosen sporadic times in order to get a wider range of values. This morning my blood sugar was 74, which is in the normal range but somewhat low compared to the rest of my values. I wonder if it was due to my using the plate method for my meals. I definitely felt like I was eating less than normal, and certainly taking in much less carbohydrate than I'm used to.
Today felt a lot more "normal" for me, as the exchange system allows you to individualize your pattern, and switch things out. For example, I could easily trade out a starch serving for a milk or a fruit, since they all have about the same carbohydrate content. The goal is to keep carbohydrate intake fairly even throughout the day, at meals and snacks. This was relatively easy since I was already doing this fairly well. The one thing I have to keep reminding myself of is that potatoes and potato chips count as a starch, not a vegetable, because their carbohydrate content is higher. I'm used to counting them as a vegetable when I plan my meals according to the MyPyramid guidelines.
Tuesday, November 9, 2010
Diabetes - Day 2
I used the plate method again to plan my meals today. My morning started, as always, with my coffee and small glass of OJ before my workout which, today, was an hour long walk. I decided to try and fit my breakfast into the plate model, so I made scrambled eggs and piece of toast, with yogurt on the side. I put Smart Balance and a small amount of pumpkin butter on the toast.
Lunch was cashew curry chicken salad on a bun with leftover vegetable soup and garlic broccoli from yesterday. A perfect plate!
I raked leaves today for about 2 hours, which was incredibly exhausting! I was dying for my afternoon snack...vanilla Chai tea (no cream or milk added) with Stevia, fruit cocktail, and Wheat Thins with the last of the Gouda cheese (sob).
We ordered takeout from a Thai restaurant for dinner tonight. I would normally order the Drunken (Spicy) noodles or Pad Thai, but both are almost 100% noodles, and not very appropriate for my current meal planning method. I scoured the menu for the best choice, and decided on a vegetable stir fry with chicken, with the rice on the side so I could control how much of it I had.
For dessert, I had another bowl of sugar free chocolate pudding (no picture).
Day two, overall , was just as good as day one. The biggest challenge I encountered was choosing something suitable from the Thai takeout place. However, the optimist in me is happy because I got to try something new (and delicious!).
I'm looking forward to tomorrow because I'll be using the exchange list for meal planning. This method is a bit more precise and is much more flexible, and will allow me to more easily include the foods I typically eat (sandwiches with two slices of bread....oatmeal....oh how I've missed you).
Lunch was cashew curry chicken salad on a bun with leftover vegetable soup and garlic broccoli from yesterday. A perfect plate!
I raked leaves today for about 2 hours, which was incredibly exhausting! I was dying for my afternoon snack...vanilla Chai tea (no cream or milk added) with Stevia, fruit cocktail, and Wheat Thins with the last of the Gouda cheese (sob).
We ordered takeout from a Thai restaurant for dinner tonight. I would normally order the Drunken (Spicy) noodles or Pad Thai, but both are almost 100% noodles, and not very appropriate for my current meal planning method. I scoured the menu for the best choice, and decided on a vegetable stir fry with chicken, with the rice on the side so I could control how much of it I had.
For dessert, I had another bowl of sugar free chocolate pudding (no picture).
Day two, overall , was just as good as day one. The biggest challenge I encountered was choosing something suitable from the Thai takeout place. However, the optimist in me is happy because I got to try something new (and delicious!).
I'm looking forward to tomorrow because I'll be using the exchange list for meal planning. This method is a bit more precise and is much more flexible, and will allow me to more easily include the foods I typically eat (sandwiches with two slices of bread....oatmeal....oh how I've missed you).
Monday, November 8, 2010
Diabetes – Day 1
For the next seven days, I will play the role of a person with diabetes. That means I’ll be planning my meals, controlling my intake of carbohydrate containing foods, and checking my blood sugar. I don’t really feel too intimidated by this assignment, because I have the impression that I already control my intake in this way. I’m pretty balanced with my food choices throughout the day, and I never binge on candy or eat large portions of high carb foods in one meal. Except when we order Chicago style pizza…which I conveniently did LAST night.
Today I used the Plate Method for meal planning. This is generally considered the simplest form of meal planning for people with diabetes, or people who just want to control their intake and lose weight. So far, my impression of this method is that it is overly simple and does not really fit in with my personal eating plan. For example, I always have cereal for breakfast and a sandwich for lunch. I also eat mixed dishes for dinner fairly often. Under the plate method, you are supposed to divide your plate into three sections: ¼ for meat, ¼ for grains or starchy vegetables, and the rest for non-starchy vegetables. Milk and fruit go on the sides, and are optional at meals. It is recommended that these foods are used for snacks. At any rate, snacks and desserts should be kept at very small portions.
Here’s what my plates looked like today:
Morning/pre-workout snack (not pictured): I always have a cup of coffee with fat free half and half, sweetened with Equal or Stevia, and ½ cup of orange juice in the morning before I work out. I usually work out for about an hour, and this keeps me going all the way until I eat breakfast.
Breakfast: small bowl of bran flakes cereal with skim milk and 1/2 banana, and a fried egg
Lunch: 1/2 turkey sandwich with Gouda cheese (yum!), a small bowl of Campbells Light Southwest vegetable soup, and fat free/no sugar added yogurt.
Afternoon snack: about ½ cup of fruit cocktail in lite syrup, and 6 Wheat Thins with peanut butter
Dinner: Extra lean beef hamburger with Gouda (yum again!), a small hamburger bun, and roasted garlic broccoli. I did have a few roasted potato wedges and about a tablespoon of ketchup. Hey, you’ve gotta have it!
Evening snack/dessert: bowl of sugar free/fat free chocolate pudding.
My overall reflection of day 1: this isn’t really that difficult. All of the foods I ate are normal for me. I often use artificially sweetened products like the yogurt and pudding. I normally would have had a whole sandwich for lunch, but this method of meal planning made me feel like I could only have one slice of bread since it fits on that part of the plate. I also would have had a lot more potatoes with my burger, but probably the same amount of broccoli.I remembered to check my blood sugar three times. Today I checked it when I got up, after my workout, and 2 hours after I ate lunch.
Today I used the Plate Method for meal planning. This is generally considered the simplest form of meal planning for people with diabetes, or people who just want to control their intake and lose weight. So far, my impression of this method is that it is overly simple and does not really fit in with my personal eating plan. For example, I always have cereal for breakfast and a sandwich for lunch. I also eat mixed dishes for dinner fairly often. Under the plate method, you are supposed to divide your plate into three sections: ¼ for meat, ¼ for grains or starchy vegetables, and the rest for non-starchy vegetables. Milk and fruit go on the sides, and are optional at meals. It is recommended that these foods are used for snacks. At any rate, snacks and desserts should be kept at very small portions.
Here’s what my plates looked like today:
Morning/pre-workout snack (not pictured): I always have a cup of coffee with fat free half and half, sweetened with Equal or Stevia, and ½ cup of orange juice in the morning before I work out. I usually work out for about an hour, and this keeps me going all the way until I eat breakfast.
Breakfast: small bowl of bran flakes cereal with skim milk and 1/2 banana, and a fried egg
Lunch: 1/2 turkey sandwich with Gouda cheese (yum!), a small bowl of Campbells Light Southwest vegetable soup, and fat free/no sugar added yogurt.
Afternoon snack: about ½ cup of fruit cocktail in lite syrup, and 6 Wheat Thins with peanut butter
Dinner: Extra lean beef hamburger with Gouda (yum again!), a small hamburger bun, and roasted garlic broccoli. I did have a few roasted potato wedges and about a tablespoon of ketchup. Hey, you’ve gotta have it!
Evening snack/dessert: bowl of sugar free/fat free chocolate pudding.
My overall reflection of day 1: this isn’t really that difficult. All of the foods I ate are normal for me. I often use artificially sweetened products like the yogurt and pudding. I normally would have had a whole sandwich for lunch, but this method of meal planning made me feel like I could only have one slice of bread since it fits on that part of the plate. I also would have had a lot more potatoes with my burger, but probably the same amount of broccoli.I remembered to check my blood sugar three times. Today I checked it when I got up, after my workout, and 2 hours after I ate lunch.
Thursday, November 4, 2010
Fatty Acid Synthesis: How fat is made
Fat is made and stored in the body any time that excess calories are taken in. It does not matter if these calories come from fat, carbohydrate, or protein. Actually, the major source of the carbon used to make fat is from carbohydrate. In general, both glucose and amino acids can be changed to Acetyl CoA, which is made into fatty acids, which is made into triglycerides, which is packaged into VLDL and circulates in the blood. Fatty acids may also be made into glycerophospholipids, which have a glycerol backbone, 2 fatty acids, and a head group.
Fatty acids are made in the liver. This is stimulated by the hormone insulin that is released after a meal. The creation of fatty acids is basically the reverse of oxidation, or the breakdown of fatty acids for energy in that, instead of breaking off two carbon units at a time, it adds them on until the long chain fatty acid palmitate is formed. However, fatty acid synthesis occurs through a different pathway with different enzymes involved. Also, fatty acids are synthesized in the cytoplasm - while oxidation occurs in the mitochondria.
In order for fatty acids to be made, acetyl CoA is needed in the cytoplasm. However, acetyl CoA cannot cross the mitochondrial membrane to get there. Acetyl CoA exists in the mitochondria because it is synthesized from pyruvate from glycolysis, using the enzyme pyruvate dehydrogenase. Normally it would enter the Krebs cycle to make energy, but when excessive carbohydrate is taken in, there is excess CoA. At that point, a special reaction takes place so that the CoA can enter the cytoplasm and make fatty acids.
With a carboxylation reaction requiring the enzyme pyruvate carboxylase and the water soluble vitamin biotin, oxaloacetate (OAA) is formed from pyruvate. This combines with acetyl CoA through a condensation reaction, forming citrate. Citrate can cross through to the cytosol, and once there it breaks back into Acetyl CoA and OAA. The acetyl CoA can now be used for fatty acid synthesis, and the OAA is changed back to pyruvate and starts the conversion process over again. This happens by first changing OAA to malate through a dehydrogenase reaction, which requires NADH. Then, malic enzyme removes one carbon and releases CO2 and NADPH, changing the malate (a 4 carbon molecule) to pyruvate (a 3 carbon molecule). The NADPH produced is then used in fatty acid synthesis. This is important, because fatty acid synthesis requires a lot of NADPH. This reaction, along with the pentose phosphate pathway, are the major sources of NADPH for fatty acid synthesis.
Acetyl CoA is converted to malonyl CoA by adding CO2 in a carboxylation reaction that requires both biotin and ATP. Malonyl CoA is the intermediate used in the fatty acid synthase complex, so at this point we are ready to make some fatty acids!
Fatty acid synthase is a large enzyme system that consists of a pantothenyl sulfhydral (P-SH) group and a cysteinal sulfhydral (C-SH) group. Acetyl CoA attaches to the P-SH group, then to the C-SH group. Malonyl CoA attaches to the P-SH group. Condensation occurs, releasing CO2 from the malonyl part. Next, a series of 4 more reactions occur which results in the addition of 2 carbons.
1. Two hydrogen are added from NADPH at the 2nd carbonyl carbon
2. Water is removed, making a double bond
3. NADPH gives more hydrogen to make the bond saturated.
4. SH is flipped to make the pantothenyl group open.
At this point, a 2 carbon unit has been added, and malonyl CoA can attach again and start the cycle over until palmitate has been made.
At this point, triglycerides may be made, or the fatty acids may be elongated or desaturated. Highly unsaturated fatty acids and a class called eicosanoids are needed for important processes in the body, including usage by the brain. However, the human body cannot desaturate an 18:1 fatty acid to 18:2 (linoleic acid) or 18:3 (linolenic acid). That's why we call these two fatty acids essential - we must obtain them from the diet.
Triglycerides are synthesized from fatty acids in the liver and adipose tissue. The process requires glycerol 3-phosphate, which is made in different ways in both tissues. The liver contains the enzyme glycerol kinase, which can change glycerol to glycerol 3-P by using ATP. The liver can also reduce the dihydroxyacetone phosphate (DHAP) from glycolysis using NADH. The adipose tissue can only do the latter, because it does not contain glycerol kinase. Either way, 2 fatty acyl CoA's are added to the glycerol 3-P to form phosphatidic acid. The phosphate group comes off, making it into a diacylglycerol. Last, another fatty acid group comes in to form a triglyceride.
The triglycerides in the liver are packaged together with cholesterol, cholesterol esters, phospholipids, and proteins (mainly ApoB-100) to form a VLDL. VLDL is composed mostly of triglyceride. Upon entering the blood the VLDL is a nascent, or new/young VLDL. As it circulates, it acquires Apo C2 and Apo E proteins from HDL, making it a mature VLDL particle. Apo C2 activates lipoprotein lipase (LPL) located at adipose and muscle cells. LPL digests the VLDL, causing triglycerides to come off. Since muscle cells need fatty acids for energy, its LPL activity is high even when the level of VLDL and chylomicrons in the blood are low. However, adipose tissue's major function is to store fatty acids. Therefore, it only uses its LPL when VLDL levels are very high, or following a meal. A meal rich in carbohydrates (namely simple sugars) results in a large amount of triglyceride being produced, leading to overproduction of VLDL. This condition is known as transient hypertriglyceridemia. As TG is broken down by the LPL in the adipose tissue, fatty acids go to storage and glycerol returns to the liver. This is how excess sugar in the diet is stored as fat and results in weight gain.
Eventually the VLDL becomes and IDL, then LDL as more of it its triglyceride content is digested.
In the fasted state, level of insulin goes down and the level of glucagon goes up. This stimulates the release of triglycerides from adipose lipase. The triglycerides are digested to fatty acids and glycerol and go to the liver. Fatty acids go through oxidation for energy, or are used to make ketones. Glycerol can be used in gluconeogenesis, or the making of glucose from non carbohydrate sources, and used for energy.
Fatty acids are made in the liver. This is stimulated by the hormone insulin that is released after a meal. The creation of fatty acids is basically the reverse of oxidation, or the breakdown of fatty acids for energy in that, instead of breaking off two carbon units at a time, it adds them on until the long chain fatty acid palmitate is formed. However, fatty acid synthesis occurs through a different pathway with different enzymes involved. Also, fatty acids are synthesized in the cytoplasm - while oxidation occurs in the mitochondria.
In order for fatty acids to be made, acetyl CoA is needed in the cytoplasm. However, acetyl CoA cannot cross the mitochondrial membrane to get there. Acetyl CoA exists in the mitochondria because it is synthesized from pyruvate from glycolysis, using the enzyme pyruvate dehydrogenase. Normally it would enter the Krebs cycle to make energy, but when excessive carbohydrate is taken in, there is excess CoA. At that point, a special reaction takes place so that the CoA can enter the cytoplasm and make fatty acids.
With a carboxylation reaction requiring the enzyme pyruvate carboxylase and the water soluble vitamin biotin, oxaloacetate (OAA) is formed from pyruvate. This combines with acetyl CoA through a condensation reaction, forming citrate. Citrate can cross through to the cytosol, and once there it breaks back into Acetyl CoA and OAA. The acetyl CoA can now be used for fatty acid synthesis, and the OAA is changed back to pyruvate and starts the conversion process over again. This happens by first changing OAA to malate through a dehydrogenase reaction, which requires NADH. Then, malic enzyme removes one carbon and releases CO2 and NADPH, changing the malate (a 4 carbon molecule) to pyruvate (a 3 carbon molecule). The NADPH produced is then used in fatty acid synthesis. This is important, because fatty acid synthesis requires a lot of NADPH. This reaction, along with the pentose phosphate pathway, are the major sources of NADPH for fatty acid synthesis.
Acetyl CoA is converted to malonyl CoA by adding CO2 in a carboxylation reaction that requires both biotin and ATP. Malonyl CoA is the intermediate used in the fatty acid synthase complex, so at this point we are ready to make some fatty acids!
Fatty acid synthase is a large enzyme system that consists of a pantothenyl sulfhydral (P-SH) group and a cysteinal sulfhydral (C-SH) group. Acetyl CoA attaches to the P-SH group, then to the C-SH group. Malonyl CoA attaches to the P-SH group. Condensation occurs, releasing CO2 from the malonyl part. Next, a series of 4 more reactions occur which results in the addition of 2 carbons.
1. Two hydrogen are added from NADPH at the 2nd carbonyl carbon
2. Water is removed, making a double bond
3. NADPH gives more hydrogen to make the bond saturated.
4. SH is flipped to make the pantothenyl group open.
At this point, a 2 carbon unit has been added, and malonyl CoA can attach again and start the cycle over until palmitate has been made.
At this point, triglycerides may be made, or the fatty acids may be elongated or desaturated. Highly unsaturated fatty acids and a class called eicosanoids are needed for important processes in the body, including usage by the brain. However, the human body cannot desaturate an 18:1 fatty acid to 18:2 (linoleic acid) or 18:3 (linolenic acid). That's why we call these two fatty acids essential - we must obtain them from the diet.
Triglycerides are synthesized from fatty acids in the liver and adipose tissue. The process requires glycerol 3-phosphate, which is made in different ways in both tissues. The liver contains the enzyme glycerol kinase, which can change glycerol to glycerol 3-P by using ATP. The liver can also reduce the dihydroxyacetone phosphate (DHAP) from glycolysis using NADH. The adipose tissue can only do the latter, because it does not contain glycerol kinase. Either way, 2 fatty acyl CoA's are added to the glycerol 3-P to form phosphatidic acid. The phosphate group comes off, making it into a diacylglycerol. Last, another fatty acid group comes in to form a triglyceride.
The triglycerides in the liver are packaged together with cholesterol, cholesterol esters, phospholipids, and proteins (mainly ApoB-100) to form a VLDL. VLDL is composed mostly of triglyceride. Upon entering the blood the VLDL is a nascent, or new/young VLDL. As it circulates, it acquires Apo C2 and Apo E proteins from HDL, making it a mature VLDL particle. Apo C2 activates lipoprotein lipase (LPL) located at adipose and muscle cells. LPL digests the VLDL, causing triglycerides to come off. Since muscle cells need fatty acids for energy, its LPL activity is high even when the level of VLDL and chylomicrons in the blood are low. However, adipose tissue's major function is to store fatty acids. Therefore, it only uses its LPL when VLDL levels are very high, or following a meal. A meal rich in carbohydrates (namely simple sugars) results in a large amount of triglyceride being produced, leading to overproduction of VLDL. This condition is known as transient hypertriglyceridemia. As TG is broken down by the LPL in the adipose tissue, fatty acids go to storage and glycerol returns to the liver. This is how excess sugar in the diet is stored as fat and results in weight gain.
Eventually the VLDL becomes and IDL, then LDL as more of it its triglyceride content is digested.
In the fasted state, level of insulin goes down and the level of glucagon goes up. This stimulates the release of triglycerides from adipose lipase. The triglycerides are digested to fatty acids and glycerol and go to the liver. Fatty acids go through oxidation for energy, or are used to make ketones. Glycerol can be used in gluconeogenesis, or the making of glucose from non carbohydrate sources, and used for energy.
Friday, October 29, 2010
More Fun With Fat: Ketone Formation
Stored fat is the major source of energy during both short term and long term fasting. During fasting, the level of glucose in the blood drops, which causes the level of insulin to drop. This stimulates the release of fatty acids into the blood, as triglycerides are broken down. The fatty acids, bound to albumin, travel mainly to the liver which converts them in one of several ways: Beta-oxidation (energy producing), ketone formation (alternate route of energy production), or to VLDL. The pathway taken will depend on conditions and the body’s needs at the moment.
Ketones are produced as an alternate source of energy, especially for the muscles and the brain, when glucose levels in the cells are extremely low, i.e. during starvation. Ketone formation goes up as the level of fatty acids in the blood increases, or starvation continues. Once starvation has continued for 2-3 days, ketones can enter the brain to be used as its energy source (the brain’s preferred source, as with other cells, is glucose).
People with diabetes (especially type 1) are prone to ketone formation, since they don’t produce insulin. If someone with type 1 diabetes does not take their insulin, glucose cannot get into their cells to be used for energy. Therefore, their body adapts by using fat as an energy source, and goes toward ketone formation if the conditions continue. It can be very dangerous if ketone levels get too high, because ketones are acids. A very acidic blood pH can result in the body’s enzymes not functioning, and this condition is known as ketoacidosis.
Ketones are produced in the liver from the CoA that is made through Beta-oxidation. The ketones formed are acetoacetate and beta-hydroxybutyrate. Two acetyl CoA’s are needed to begin the process, which are the same two from the final cycle of beta-oxidation. Normally, these two would just go on to the TCA cycle to make energy, but when acetyl CoA is very high, due to such a large amount of fatty acid stores being used for energy, ketone formation will occur.
1.The first reaction is catalyzed by the enzyme thiolase, and causes the two molecules of acetyl CoA to join into one molecule of acetoacetyl CoA.
2.The second reaction uses the enzyme HMG CoA synthase and acetyl CoA to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA)
3.Next, HMG-CoA is cleaved by HMG-CoA lyase to form acetyl CoA and acetoacetate, while losing a hydrogen.
The acetoacetate may enter the blood directly, or form the other major ketone, Beta-hydroxybutyrate, with the enzyme Beta-hydroxybutyrate dehydrogenase which adds a hydrogen at the second carbonyl carbon. Or, as an alternate, acetoacetate may become acetone, which mainly gets expired by the lungs.
The ketones can go on to make energy in muscle and skeletal tissue. Nearly all cell and tissue types, aside from the liver and red blood cells, can use ketones. In the mitochondrial matrix, the beta-hydroxybutyrate is oxidized back to acetoacetate, with the help of the enzyme beta-hydroxybutyrate dehydrogenase, which produces NADH. Acetoacetate then accepts a CoA group from succinyl in a transferase reaction. This results in the formation of acetoacetyl CoA, which can then be broken into 2 acetyl CoA’s with a thiolase enzyme reaction. These acetyl CoA’s then enter the TCA cycle to make energy.
Even during prolonged fasting (30-40 days) levels of glucose and free fatty acids remain constant. A person can actually live this long without food by using their fat stores, and eventually their muscle protein stores. The use of ketones for energy is an adaptive measure taken by the body to spare muscle protein for as long as possible. The level of glucose can stay constant because, although it tries to keep it minimal, the body can make glucose from the amino acids being released from the muscle.
Ketones are produced as an alternate source of energy, especially for the muscles and the brain, when glucose levels in the cells are extremely low, i.e. during starvation. Ketone formation goes up as the level of fatty acids in the blood increases, or starvation continues. Once starvation has continued for 2-3 days, ketones can enter the brain to be used as its energy source (the brain’s preferred source, as with other cells, is glucose).
People with diabetes (especially type 1) are prone to ketone formation, since they don’t produce insulin. If someone with type 1 diabetes does not take their insulin, glucose cannot get into their cells to be used for energy. Therefore, their body adapts by using fat as an energy source, and goes toward ketone formation if the conditions continue. It can be very dangerous if ketone levels get too high, because ketones are acids. A very acidic blood pH can result in the body’s enzymes not functioning, and this condition is known as ketoacidosis.
Ketones are produced in the liver from the CoA that is made through Beta-oxidation. The ketones formed are acetoacetate and beta-hydroxybutyrate. Two acetyl CoA’s are needed to begin the process, which are the same two from the final cycle of beta-oxidation. Normally, these two would just go on to the TCA cycle to make energy, but when acetyl CoA is very high, due to such a large amount of fatty acid stores being used for energy, ketone formation will occur.
1.The first reaction is catalyzed by the enzyme thiolase, and causes the two molecules of acetyl CoA to join into one molecule of acetoacetyl CoA.
2.The second reaction uses the enzyme HMG CoA synthase and acetyl CoA to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA)
3.Next, HMG-CoA is cleaved by HMG-CoA lyase to form acetyl CoA and acetoacetate, while losing a hydrogen.
The acetoacetate may enter the blood directly, or form the other major ketone, Beta-hydroxybutyrate, with the enzyme Beta-hydroxybutyrate dehydrogenase which adds a hydrogen at the second carbonyl carbon. Or, as an alternate, acetoacetate may become acetone, which mainly gets expired by the lungs.
The ketones can go on to make energy in muscle and skeletal tissue. Nearly all cell and tissue types, aside from the liver and red blood cells, can use ketones. In the mitochondrial matrix, the beta-hydroxybutyrate is oxidized back to acetoacetate, with the help of the enzyme beta-hydroxybutyrate dehydrogenase, which produces NADH. Acetoacetate then accepts a CoA group from succinyl in a transferase reaction. This results in the formation of acetoacetyl CoA, which can then be broken into 2 acetyl CoA’s with a thiolase enzyme reaction. These acetyl CoA’s then enter the TCA cycle to make energy.
Even during prolonged fasting (30-40 days) levels of glucose and free fatty acids remain constant. A person can actually live this long without food by using their fat stores, and eventually their muscle protein stores. The use of ketones for energy is an adaptive measure taken by the body to spare muscle protein for as long as possible. The level of glucose can stay constant because, although it tries to keep it minimal, the body can make glucose from the amino acids being released from the muscle.
Thursday, October 28, 2010
More Fun with Fat: Fatty Acid Oxidation
This week is about how fat is used to make energy.
Beta-oxidation is the process that fat undergoes which produces large amounts of energy. This process occurs within the mitochondrial matrix of the cells. Between meals, during fasting, or during prolonged exercise, fatty acids are released from the adipose tissue in response to a drop in insulin and an increase in glucagon. The main type of fats released are the long-chain fatty acids palmitate (C-16), oleate (C-18), and stearate (C-18:1), since these encompass the highest proportion of fats consumed in the diet and also synthesized in the body.
When these fatty acids enter the blood, they cannot travel far without assistance because they are extremely hydrophobic. Therefore, they bind to albumin, which is the major protein in the blood. Once they reach the cells, they still need a lot of help to get inside. They are able to enter the cell by binding to a fatty acid binding protein located at the plasma membrane, which facilitates their transport through. Once in the cytosol, the fatty acid becomes activated by reacting with ATP and coenzyme A (CoA), making it into a fatty acyl CoA.
At this point, fatty acyl CoA may take several paths:
1. It can go on into the mitochondrial matrix to undergo Beta-oxidation or ketogenesis and create energy.
2. It can go to storage in the form of triglyceride
3. It can become part of phospholipids or sphingolipids
If fatty acyl CoA goes toward energy formation, it can pass through into the outer mitochondrial membrane alone. However, it still needs help to cross the inner membrane, again due to being hydrophobic. It goes through the inner mitochondrial membrane by binding with carnitine and becoming fatty acyl carnitine. Carnitine is made from the essential amino acids lysine and methionine. Therefore, carnitine is not an essential amino acid because it is synthesized in the body. Carnitine contains nitrogen and oxygen, which gives it charges - allowing it to react with water. That is why it is needed to cross the membrane.
Once across the inner membrane, carnitine comes off and CoA attaches back, catalyzed by the enzyme carnitine palmitoyltransferase I (CPTI) to the fatty acyl, making it back into fatty acyl CoA. At this point, it is ready to undergo Beta-oxidation inside the mitochondrial matrix.
Beta-oxidation is a spiral-like pathway that continues to cleave the fatty acyl by two-carbon acetyl CoA units, beginning at the carboxyl end of the molecule, until only a 4 carbon fatty acyl CoA remains, which is broken into 2 acetyl CoA's.
Beta-oxidation consists of four different types of reactions.
1. the first reaction, catalyzed by acyl CoA dehydrogenase, results in a double bond with the trans configuration when hydrogen is transferred from between the alpha and beta carbons to FAD to make FAH(2H).
2. the second reaction, catalyzed by enoyl CoA hydratase, adds an OH group to the Beta carbon, and an H to the alpha carbon.
3. The third reaction, catalyzed by beta-hydroxyacyl CoA dehydrogenase, the OH group on the beta carbon is oxidized and forms a ketone. 2 hydrogen get transferred to NAD+, forming NADH+H+. This results in the beta-carbon becoming the carbonyl carbon.
4. The last step is catalyzed by Beta-ketothiolase, and in this step the bond between the alpha and beta carbons is broken, releasing acetyl CoA, and resulting in a new fatty acyl CoA that is 2 carbons shorter.
The new fatty acyl CoA will go through several more cycles of Beta-oxidation, losing 2 more carbons each time, until only a 4 carbon unit is left-which is broken to two molecules of acetyl CoA. These acetyl CoA's can then enter the TCA, or Kreb's, cycle.
This results in a very large amount of energy being produced, because each Acetyl CoA that enters the Kreb's cycle makes 10 ATP.
So, if a 16 carbon fatty acyl like palmytic acid goes through oxidation, it goes through 7 total cycles (number of cycles=number of carbon/2 - 1). This makes 8 acetyl CoA (number of acetyl CoA=number of carbon/2). So, 8 acetyl CoA's go through Kreb's and make 10 ATP each - that's 80 ATP so far.
Also, each cycle of Beta-oxidation produces 1 NADH2 and 1 FADH2. In this case, 7 cycles yields 7 of each. These also enter the Kreb's cycle. Each NADH2 can make 2.5 ATP - so there's another 17.5 ATP. FADH2 can each make 1.5 ATP - an additional 10.5.
All together, the complete oxidation of a 16 carbon fatty acid can make 108 ATP - but we have to subtract 2 of these, because 2 are used to initially make it into a fatty acyl CoA. A small price to pay - we still get a net gain of 106 ATP.
In comparison, the complete oxidation of one glucose molecule only generates 32 ATP. So, fat is a very important source of energy in our diet. It may cost us a lot of calories (9 calories per gram, compared to carbohydrates and protein, which are 4 calories per gram) but it gives a lot back!
Beta-oxidation is the process that fat undergoes which produces large amounts of energy. This process occurs within the mitochondrial matrix of the cells. Between meals, during fasting, or during prolonged exercise, fatty acids are released from the adipose tissue in response to a drop in insulin and an increase in glucagon. The main type of fats released are the long-chain fatty acids palmitate (C-16), oleate (C-18), and stearate (C-18:1), since these encompass the highest proportion of fats consumed in the diet and also synthesized in the body.
When these fatty acids enter the blood, they cannot travel far without assistance because they are extremely hydrophobic. Therefore, they bind to albumin, which is the major protein in the blood. Once they reach the cells, they still need a lot of help to get inside. They are able to enter the cell by binding to a fatty acid binding protein located at the plasma membrane, which facilitates their transport through. Once in the cytosol, the fatty acid becomes activated by reacting with ATP and coenzyme A (CoA), making it into a fatty acyl CoA.
At this point, fatty acyl CoA may take several paths:
1. It can go on into the mitochondrial matrix to undergo Beta-oxidation or ketogenesis and create energy.
2. It can go to storage in the form of triglyceride
3. It can become part of phospholipids or sphingolipids
If fatty acyl CoA goes toward energy formation, it can pass through into the outer mitochondrial membrane alone. However, it still needs help to cross the inner membrane, again due to being hydrophobic. It goes through the inner mitochondrial membrane by binding with carnitine and becoming fatty acyl carnitine. Carnitine is made from the essential amino acids lysine and methionine. Therefore, carnitine is not an essential amino acid because it is synthesized in the body. Carnitine contains nitrogen and oxygen, which gives it charges - allowing it to react with water. That is why it is needed to cross the membrane.
Once across the inner membrane, carnitine comes off and CoA attaches back, catalyzed by the enzyme carnitine palmitoyltransferase I (CPTI) to the fatty acyl, making it back into fatty acyl CoA. At this point, it is ready to undergo Beta-oxidation inside the mitochondrial matrix.
Beta-oxidation is a spiral-like pathway that continues to cleave the fatty acyl by two-carbon acetyl CoA units, beginning at the carboxyl end of the molecule, until only a 4 carbon fatty acyl CoA remains, which is broken into 2 acetyl CoA's.
Beta-oxidation consists of four different types of reactions.
1. the first reaction, catalyzed by acyl CoA dehydrogenase, results in a double bond with the trans configuration when hydrogen is transferred from between the alpha and beta carbons to FAD to make FAH(2H).
2. the second reaction, catalyzed by enoyl CoA hydratase, adds an OH group to the Beta carbon, and an H to the alpha carbon.
3. The third reaction, catalyzed by beta-hydroxyacyl CoA dehydrogenase, the OH group on the beta carbon is oxidized and forms a ketone. 2 hydrogen get transferred to NAD+, forming NADH+H+. This results in the beta-carbon becoming the carbonyl carbon.
4. The last step is catalyzed by Beta-ketothiolase, and in this step the bond between the alpha and beta carbons is broken, releasing acetyl CoA, and resulting in a new fatty acyl CoA that is 2 carbons shorter.
The new fatty acyl CoA will go through several more cycles of Beta-oxidation, losing 2 more carbons each time, until only a 4 carbon unit is left-which is broken to two molecules of acetyl CoA. These acetyl CoA's can then enter the TCA, or Kreb's, cycle.
This results in a very large amount of energy being produced, because each Acetyl CoA that enters the Kreb's cycle makes 10 ATP.
So, if a 16 carbon fatty acyl like palmytic acid goes through oxidation, it goes through 7 total cycles (number of cycles=number of carbon/2 - 1). This makes 8 acetyl CoA (number of acetyl CoA=number of carbon/2). So, 8 acetyl CoA's go through Kreb's and make 10 ATP each - that's 80 ATP so far.
Also, each cycle of Beta-oxidation produces 1 NADH2 and 1 FADH2. In this case, 7 cycles yields 7 of each. These also enter the Kreb's cycle. Each NADH2 can make 2.5 ATP - so there's another 17.5 ATP. FADH2 can each make 1.5 ATP - an additional 10.5.
All together, the complete oxidation of a 16 carbon fatty acid can make 108 ATP - but we have to subtract 2 of these, because 2 are used to initially make it into a fatty acyl CoA. A small price to pay - we still get a net gain of 106 ATP.
In comparison, the complete oxidation of one glucose molecule only generates 32 ATP. So, fat is a very important source of energy in our diet. It may cost us a lot of calories (9 calories per gram, compared to carbohydrates and protein, which are 4 calories per gram) but it gives a lot back!
Saturday, October 23, 2010
Limited Resource Audiences
A person's resources may include many things besides money. There are also emotional (the stamina to keep going when things are hard/avoid engaging in destructive behaviors), mental (ability to deal with daily life), spiritual (faith, sense of community), and physical (mobility that allows one to be self sufficient and take care of themselves and their family) resources.
Those who are limited in some or all of these resources may be difficult to reach with normal educational techniques. For example, long term planning is not something that is commonly used by this group. This is because they are used to survival tactics which force them to do whatever is needed at the moment. Therefore, it is more effective to focus on the now and use short term goal setting, and avoid talking about the implications which could occur the long term future. Only "need to know" information should be given, rather than "nice to know".
When working with this population it is important to recognize the fact that there may be a sense of failure related to education. Many may not have completed school and will see anything "school like" as a challenge that is too big for them to handle. Therefore "classes" should be kept very casual and held in familiar surroundings (community centers, or other places participants frequent). They should be fun and include games/activities to keep participants interested. Activities should be achievable in order to preserve participants self esteem.
Those who are limited in some or all of these resources may be difficult to reach with normal educational techniques. For example, long term planning is not something that is commonly used by this group. This is because they are used to survival tactics which force them to do whatever is needed at the moment. Therefore, it is more effective to focus on the now and use short term goal setting, and avoid talking about the implications which could occur the long term future. Only "need to know" information should be given, rather than "nice to know".
When working with this population it is important to recognize the fact that there may be a sense of failure related to education. Many may not have completed school and will see anything "school like" as a challenge that is too big for them to handle. Therefore "classes" should be kept very casual and held in familiar surroundings (community centers, or other places participants frequent). They should be fun and include games/activities to keep participants interested. Activities should be achievable in order to preserve participants self esteem.
Digestion and absorption of dietary lipids, OR More than you ever wanted to know about what happens to food after you swallow it
The fat in our diet consists mainly of triglycerides (95%), with the other 5% being phospholipids, cholesterol and cholesterol esters, and fat soluble vitamins. Digestion of fat begins minimally in the mouth with the enzyme lingual lipase, and in the stomach with gastric lipase. These lipases mainly break down milk fats, which have short and medium chain fatty acids. Most of the fat in our diet is long chain.
This fat enters the small intestine intact, where the gut hormone CCK is released and stimulates the release of bile, pancreatic lipase, and colipase. The hormone secretin stimulates the release of bicarbonate, which helps keep a less acidic atmosphere so that enzymes can become active.
Bile is made from cholesterol in the liver and stored in the gallbladder. It is released in response to CCK and acts in the small intestine. It acts as an emulsifier and breaks the fat into smaller particles, which increases the surface area so that pancreatic lipase can attack it more easily. Once bile has finished its job it continues on to the ileum of the small intestine where 90% of it is reabsorbed, returning to the liver (enterhepatic cycle). The rest goes to the colon and is excreted. The entire pool of bile is recycled twice per fat containing meal. Soluble fibers from our diet and some cholesterol lowering drugs bind to bile so that more of it is excreted. This can help lower blood cholesterol.
Pancreatic lipase breaks the bonds connecting the fatty acids on carbon #1 and #3 of the triglycerides. This results in free fatty acids, 2-monoacylglycerol, and some glycerol.
Cholesterol esters are broken down to cholesterol by the enzyme cholesterol enterase. Phospholipids are broken down to lysophospholipids by the enzyme phospholipase.
Short and medium chain fatty acids are water miscible, so they can be absorbed directly from the intestinal cell to the portal vein, which brings them to the liver. In order to absorb long chain fatty acids, they must be packaged into a delivery device called a micelle. Micelles are tiny droplets emulsified by bile salts which contain all of the remaining dietary components (long chain fatty acids, 2-monoglycerides, glycerol, fat soluble vitamins, cholesterol, and lysophospholipids) along with bile. Micelles bring these lumps of particles to the microville of the small intestine, where everything except the bile gets absorbed into the cell.
But the fun doesn't stop here! Inside the intestinal cell, the dietary particles are rebuilt, once again, into triglycerides. The fatty acids are activated to fatty acyl coenzyme A (FACoA). FACoA reacts with 2-monoacylglycerol to form a diacylglycerol, and then with another to reform a triglyceride.
The triglycerides are very hydrophobic and cannot be transported alone, so they get packed with apoproteins (mainly B-48), phospholipids, cholesterol and vitamins to form what is known as a chylomicron. Chylomicrons are a type of lipoprotein. They are mainly made of triglyceride because they are representative of the fat in our diet. They have a single layer of phospholipid on the outside with the hydrophillic end facing out, which keeps water from entering. The hydrophobic components are hidden on the inside. The apoproteins sit on the outside of the structure. Chylomicrons are too large to go directly into the blood, so they enter the lymphatic system. They circulate to the thoracic duct and enter the bloodstream from there. As a chylomicron matures it receives more apoproteins upon its surface from HDL. ApoE and ApoCII are only found on these mature chylomicrons, and both serve important purposes. The enzyme lipoprotein lipase is activated based upon the presence of ApoCII. Lipoprotein lipase is found in the capillaries of the adipose and muscle cells, and interacts with the chylomicron and digests some of the triglycerides into fatty acids and glycerol. The fatty acids are taken up for storage into adipose and/or muscle cells, and the glycerol goes to the liver. What is left over is called a chylomicron remnant, and is returned to the liver. The presence of ApoE on the chylomicron remnant allows it to be recognized by the liver cells so that it can enter them by endocytosis and get digested by lysosomes and its contents reused.
The triglyceride components get reused, along with newly synthesized triglycerides, by creating VLDL in the liver. VLDL gets released into the bloodstream, where some of the triglycerides get taken up by adipose cells. The VLDL then becomes IDL (intermediate density lipoprotein) or LDL.
This fat enters the small intestine intact, where the gut hormone CCK is released and stimulates the release of bile, pancreatic lipase, and colipase. The hormone secretin stimulates the release of bicarbonate, which helps keep a less acidic atmosphere so that enzymes can become active.
Bile is made from cholesterol in the liver and stored in the gallbladder. It is released in response to CCK and acts in the small intestine. It acts as an emulsifier and breaks the fat into smaller particles, which increases the surface area so that pancreatic lipase can attack it more easily. Once bile has finished its job it continues on to the ileum of the small intestine where 90% of it is reabsorbed, returning to the liver (enterhepatic cycle). The rest goes to the colon and is excreted. The entire pool of bile is recycled twice per fat containing meal. Soluble fibers from our diet and some cholesterol lowering drugs bind to bile so that more of it is excreted. This can help lower blood cholesterol.
Pancreatic lipase breaks the bonds connecting the fatty acids on carbon #1 and #3 of the triglycerides. This results in free fatty acids, 2-monoacylglycerol, and some glycerol.
Cholesterol esters are broken down to cholesterol by the enzyme cholesterol enterase. Phospholipids are broken down to lysophospholipids by the enzyme phospholipase.
Short and medium chain fatty acids are water miscible, so they can be absorbed directly from the intestinal cell to the portal vein, which brings them to the liver. In order to absorb long chain fatty acids, they must be packaged into a delivery device called a micelle. Micelles are tiny droplets emulsified by bile salts which contain all of the remaining dietary components (long chain fatty acids, 2-monoglycerides, glycerol, fat soluble vitamins, cholesterol, and lysophospholipids) along with bile. Micelles bring these lumps of particles to the microville of the small intestine, where everything except the bile gets absorbed into the cell.
But the fun doesn't stop here! Inside the intestinal cell, the dietary particles are rebuilt, once again, into triglycerides. The fatty acids are activated to fatty acyl coenzyme A (FACoA). FACoA reacts with 2-monoacylglycerol to form a diacylglycerol, and then with another to reform a triglyceride.
The triglycerides are very hydrophobic and cannot be transported alone, so they get packed with apoproteins (mainly B-48), phospholipids, cholesterol and vitamins to form what is known as a chylomicron. Chylomicrons are a type of lipoprotein. They are mainly made of triglyceride because they are representative of the fat in our diet. They have a single layer of phospholipid on the outside with the hydrophillic end facing out, which keeps water from entering. The hydrophobic components are hidden on the inside. The apoproteins sit on the outside of the structure. Chylomicrons are too large to go directly into the blood, so they enter the lymphatic system. They circulate to the thoracic duct and enter the bloodstream from there. As a chylomicron matures it receives more apoproteins upon its surface from HDL. ApoE and ApoCII are only found on these mature chylomicrons, and both serve important purposes. The enzyme lipoprotein lipase is activated based upon the presence of ApoCII. Lipoprotein lipase is found in the capillaries of the adipose and muscle cells, and interacts with the chylomicron and digests some of the triglycerides into fatty acids and glycerol. The fatty acids are taken up for storage into adipose and/or muscle cells, and the glycerol goes to the liver. What is left over is called a chylomicron remnant, and is returned to the liver. The presence of ApoE on the chylomicron remnant allows it to be recognized by the liver cells so that it can enter them by endocytosis and get digested by lysosomes and its contents reused.
The triglyceride components get reused, along with newly synthesized triglycerides, by creating VLDL in the liver. VLDL gets released into the bloodstream, where some of the triglycerides get taken up by adipose cells. The VLDL then becomes IDL (intermediate density lipoprotein) or LDL.
Friday, October 22, 2010
Fat is where it's at
This week's topic is lipids, AKA fat. Lipids are water insoluble, or immiscible. They are, however, soluble in some organic solvents such as acetone and benzene. Lipids are a very concentrated source of energy, and therefore may contribute to obesity, which contributes to the mortality rate in the US. Types of lipids include fatty acids, triglycerides, phospholipids, cholesterol, eicosanoids, lipoproteins, and the fat soluble vitamins A, D, E, and K.
The fat cells in our body (also known as adipocytes or adipose tissue) serve to store fat. The form that fat is stored in is triacyglycerol, or triglyceride.
Fatty acids are not found alone in nature or in the body. They are part of the structure of triacylglycerols. The structure of fatty acids is a chain of CH with carboxyl group (COOH) at one end of the chain. A saturated fatty acid has no double bonds. Unsaturated fatty acids have at least one double bond. Monounsaturated has one double bond, and polyunsaturated has two or more double bonds.
The number of carbons in fatty acids is usually an even number in nature. The most abundant have 16, 18, or 20 carbons.
To name the fatty acid, you start at the carboxyl group end and number the carbons. Then you count the number of double bonds and note it like this - example 18:1 is a fatty acid with an 18 carbon chain and one double bond. In this case, the double bond occurs between carbon # 9 and # 10, so you note this by adding a delta 9 after the name. This one is 18:1 (delta)9, or oleic acid. A fatty acid named 18:2 (delta) 9,12 has 18 carbons and two double bonds, occurring at carbon #9 and #12. There is always a difference of 3 carbons between the double bonds.
Monounsaturated and polyunsaturated fats come from plant sources and include canola oil and olive oil (mono) and vegetable, sunflower, and safflower oil (poly).
Tropical oils include palm and coconut. Although they come from plant sources, they are highly saturated and should be limited. This is confusing to some people because typically saturated fats are more solid at room temperature. Tropical oils appear more liquid at room temperature due to their content of shorter chains of fatty acids.
Most saturated fats are from animal sources: butter, beef fat, and lard.
The essential fatty acids are omega 6 (linoleic acid) and omega 3 (linolenic acid). They are essential because they cannot be synthesized in the body and must be obtained from the diet.
The omega fatty acids are named differently than others. Instead of starting the numbering at the carboxyl end, you start at the methyl end. So the first double bond on an omega 3 fatty acid is at the 3rd carbon from the methyl end.
Omega 3 fatty acids have been shown to decrease the incidence of cardiovascular disease (CVD) by decreasing blood cholesterol levels and lowering blood clotting. They are also thought to be good for brain development and functioning, vision, the immune system, and memory. Linolenic acid is just one type of omega 3 fatty acid, and comes from plant sources. Other types, such as eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA) come from fish oils. EPA and DHA are both highly unsaturated. EPA contains 5 double bonds, and DHA contains 6. Omega 3 fatty acids produce the important biomolecules prostoglandins, leukotrienes, and thromboxanes.
Hydrogenation is a process that turns polyunsaturated fats into saturated fats by adding hydrogen at the double bonds. This process generates trans fatty acids when vegetable oils are partially hydrogenated - i.e. not all of the double bonds are filled with hydrogen. When this happens the double bond is twisted from the cis (hydrogens are on the same side of the double bond) to trans (hydrogens are on opposite sides of the double bond). If the fat gets fully hydrogenated, this makes a saturated fatty acid, not a trans fat.
Trans fats are a huge health concern because they increase the risk of heart disease. They increase bad cholesterol and prevent good fats from functioning, promoting heart disease and circulatory disorders. They also depress the immune system, interfere with pregnancy (can cause low birth weights and poorer quality of breast milk), increase insulin resistance which can worsen diabetes and hypertension, and disturb liver function.
Other reactions that fat can undergo include emulsification, oxidation, and anti-oxidation.
Emulsification is the breaking of large fat molecules into smaller particles, such as the homogenization of milk. Bile and lecithin are able to undergo this process.
Oxidation results in the spoilage/rancidity of fats. This occurs when the double bond forms a peroxide and results in a bad taste and smell.
The fat soluble vitamin E can act as an antioxidant, and prevent spoilage. That is why it is added to products that contain fat. Vegetable oil naturally has some vitamin E in it, but more is often added to prolong shelf life.
Triglycerides are what we typically think of when we think of fat. It is the most abundant form both in our body and in nature (up to 95% of all fat). It is a neutral fat, meaning it is not polar and does not react with water.
The structure of a triglyceride is a glycerol with 3 fatty acids (acyl groups) attached, or estrified.
A diglyceride would have two attached fatty acids, and a monoglyceride would have 1.
Glycerol is the backbone of these structures. It contains 3 carbons with a hydroxyl group. The fatty acids get attached to the carbons in this backbone. In a monoglyceride, the fatty acid is attached to carbon #1. On a diglyceride, the fatty acid groups are attached to carbon #1 and #3.
Phospholipids are another important type of lipid. They are known as structural lipids because they are the main lipid found in the plasma membrane of cells. Human cells are all different, but the common feature is the plasma membrane. It keeps the structure of the cell intact which allows all of its contents to stay inside.
Human/animal cells also contain the glycocalyx, a carbohydrate rich area that includes glycoprotein and glycolipids.
Proteins in the cell may be integral (penetrating the cell membrane) or peripheral (stay on the surface of the membrane).
Cholesterol is also found in the plasma membrane. It has a 4 ring structure, and like phospholipid has a polar OH group which is hydrophyllic, and a tail group (including the ring structure) that is hydrophobic and hides inside the membrane. Cholesterol is synthesized in the body and is used to make cholic acid, which is part of bile. Because it is both hydrophobic and hydrophillic it can act as an emulsifier. Cholesterol is also used to make hormones like estradiol, a female sex hormone.
There are 4 types of transport mechanisms for moving molecules through the plasma membrane of cells: diffusion (simple or facilitated), active transport, and endocytosis.
Diffusion allows molecules to move from areas of high concentration to areas of low concentration, without requiring energy because it is a passive process. Simple diffusion simply moves the molecules/ions between lipids or other parts of the membrane. Sometimes pores are formed, which are known as gated channels for them to move through.
Facilitative diffusion requires a carrier protein which attaches to the molecule and undergoes a transformational change, allowing the molecule to move through.
Active transport also requires a carrier molecule, as well as energy. It allows movement from areas of low concentration to high concentration. An example is Sodium/potassium/ATPase in which energy is released when sodium binds to the carrier protein, releasing ADP and phosphate. Phosphate then attaches and undergoes a conformational change, dumping sodium into the extracellular fluid. Potassium then attaches at the binding site, releasing the phosphate group and undergoing another conformational change which in turn brings in the molecule and released potassium inside the cell.
Endocytosis occurs when the molecules approach the membrane, and it folds in to move them inside the cell.
Saturation phenomenon is the idea that the maximum velocity has been reached when all of the binding sites of transporter proteins are occupied.
Phospholipids are polar lipids, meaning that they contain molecules that react with water, such as nitrogen and oxygen. The basic structure is a glycerol backbone with 2 fatty acid chains plus a phosphate group. There will be another group attached to the phosphate group, known as the head group, which allows for classification of that specific phospholipid.
Phospholipids are distinct in that they contain a polar head and a hydrophobic tail in the same molecule. Because of this they are called ampipathic molecules. The head is hydrophillic (likes to react with water) and the tail is hydrophobic, or immiscible (does not like to react with water). This allows them to form a structural bilayer in the cell membrane. The hydrophyllic ends face outward while the hydrophobic ends remain inward. Lecithin is the major phospholipid found in the membrane. It can be synthesized in the body, but is also found in foods such as liver, egg yolk, and soybeans. Lecithin is an effective emulsifier.
Phospholipids are also found in lipoproteins, which are the transport vehicles for lipid in the blood. Lipids need help being transported because they are water immiscible. Therefore, they are hidden inside the lipoproteins. The hydrophyllic part of the phospholipid faces outward from the surface of the lipoprotein to allow it to freely move through the blood.
There are several types of lipoproteins: chylomicrons, which are made in the intestine; VLDL, which is made in the intestine and liver; LDL, which is made from VLDL in the blood; and HDL, which is made in the intestine and liver. The density depends upon the amount of protein and fat. A chylomicron has the highest amount of fat and the lowest protein, so it is the lowest density. HDL is the highest density due to its high protein content relative to fat.
The fat cells in our body (also known as adipocytes or adipose tissue) serve to store fat. The form that fat is stored in is triacyglycerol, or triglyceride.
Fatty acids are not found alone in nature or in the body. They are part of the structure of triacylglycerols. The structure of fatty acids is a chain of CH with carboxyl group (COOH) at one end of the chain. A saturated fatty acid has no double bonds. Unsaturated fatty acids have at least one double bond. Monounsaturated has one double bond, and polyunsaturated has two or more double bonds.
The number of carbons in fatty acids is usually an even number in nature. The most abundant have 16, 18, or 20 carbons.
To name the fatty acid, you start at the carboxyl group end and number the carbons. Then you count the number of double bonds and note it like this - example 18:1 is a fatty acid with an 18 carbon chain and one double bond. In this case, the double bond occurs between carbon # 9 and # 10, so you note this by adding a delta 9 after the name. This one is 18:1 (delta)9, or oleic acid. A fatty acid named 18:2 (delta) 9,12 has 18 carbons and two double bonds, occurring at carbon #9 and #12. There is always a difference of 3 carbons between the double bonds.
Monounsaturated and polyunsaturated fats come from plant sources and include canola oil and olive oil (mono) and vegetable, sunflower, and safflower oil (poly).
Tropical oils include palm and coconut. Although they come from plant sources, they are highly saturated and should be limited. This is confusing to some people because typically saturated fats are more solid at room temperature. Tropical oils appear more liquid at room temperature due to their content of shorter chains of fatty acids.
Most saturated fats are from animal sources: butter, beef fat, and lard.
The essential fatty acids are omega 6 (linoleic acid) and omega 3 (linolenic acid). They are essential because they cannot be synthesized in the body and must be obtained from the diet.
The omega fatty acids are named differently than others. Instead of starting the numbering at the carboxyl end, you start at the methyl end. So the first double bond on an omega 3 fatty acid is at the 3rd carbon from the methyl end.
Omega 3 fatty acids have been shown to decrease the incidence of cardiovascular disease (CVD) by decreasing blood cholesterol levels and lowering blood clotting. They are also thought to be good for brain development and functioning, vision, the immune system, and memory. Linolenic acid is just one type of omega 3 fatty acid, and comes from plant sources. Other types, such as eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA) come from fish oils. EPA and DHA are both highly unsaturated. EPA contains 5 double bonds, and DHA contains 6. Omega 3 fatty acids produce the important biomolecules prostoglandins, leukotrienes, and thromboxanes.
Hydrogenation is a process that turns polyunsaturated fats into saturated fats by adding hydrogen at the double bonds. This process generates trans fatty acids when vegetable oils are partially hydrogenated - i.e. not all of the double bonds are filled with hydrogen. When this happens the double bond is twisted from the cis (hydrogens are on the same side of the double bond) to trans (hydrogens are on opposite sides of the double bond). If the fat gets fully hydrogenated, this makes a saturated fatty acid, not a trans fat.
Trans fats are a huge health concern because they increase the risk of heart disease. They increase bad cholesterol and prevent good fats from functioning, promoting heart disease and circulatory disorders. They also depress the immune system, interfere with pregnancy (can cause low birth weights and poorer quality of breast milk), increase insulin resistance which can worsen diabetes and hypertension, and disturb liver function.
Other reactions that fat can undergo include emulsification, oxidation, and anti-oxidation.
Emulsification is the breaking of large fat molecules into smaller particles, such as the homogenization of milk. Bile and lecithin are able to undergo this process.
Oxidation results in the spoilage/rancidity of fats. This occurs when the double bond forms a peroxide and results in a bad taste and smell.
The fat soluble vitamin E can act as an antioxidant, and prevent spoilage. That is why it is added to products that contain fat. Vegetable oil naturally has some vitamin E in it, but more is often added to prolong shelf life.
Triglycerides are what we typically think of when we think of fat. It is the most abundant form both in our body and in nature (up to 95% of all fat). It is a neutral fat, meaning it is not polar and does not react with water.
The structure of a triglyceride is a glycerol with 3 fatty acids (acyl groups) attached, or estrified.
A diglyceride would have two attached fatty acids, and a monoglyceride would have 1.
Glycerol is the backbone of these structures. It contains 3 carbons with a hydroxyl group. The fatty acids get attached to the carbons in this backbone. In a monoglyceride, the fatty acid is attached to carbon #1. On a diglyceride, the fatty acid groups are attached to carbon #1 and #3.
Phospholipids are another important type of lipid. They are known as structural lipids because they are the main lipid found in the plasma membrane of cells. Human cells are all different, but the common feature is the plasma membrane. It keeps the structure of the cell intact which allows all of its contents to stay inside.
Human/animal cells also contain the glycocalyx, a carbohydrate rich area that includes glycoprotein and glycolipids.
Proteins in the cell may be integral (penetrating the cell membrane) or peripheral (stay on the surface of the membrane).
Cholesterol is also found in the plasma membrane. It has a 4 ring structure, and like phospholipid has a polar OH group which is hydrophyllic, and a tail group (including the ring structure) that is hydrophobic and hides inside the membrane. Cholesterol is synthesized in the body and is used to make cholic acid, which is part of bile. Because it is both hydrophobic and hydrophillic it can act as an emulsifier. Cholesterol is also used to make hormones like estradiol, a female sex hormone.
There are 4 types of transport mechanisms for moving molecules through the plasma membrane of cells: diffusion (simple or facilitated), active transport, and endocytosis.
Diffusion allows molecules to move from areas of high concentration to areas of low concentration, without requiring energy because it is a passive process. Simple diffusion simply moves the molecules/ions between lipids or other parts of the membrane. Sometimes pores are formed, which are known as gated channels for them to move through.
Facilitative diffusion requires a carrier protein which attaches to the molecule and undergoes a transformational change, allowing the molecule to move through.
Active transport also requires a carrier molecule, as well as energy. It allows movement from areas of low concentration to high concentration. An example is Sodium/potassium/ATPase in which energy is released when sodium binds to the carrier protein, releasing ADP and phosphate. Phosphate then attaches and undergoes a conformational change, dumping sodium into the extracellular fluid. Potassium then attaches at the binding site, releasing the phosphate group and undergoing another conformational change which in turn brings in the molecule and released potassium inside the cell.
Endocytosis occurs when the molecules approach the membrane, and it folds in to move them inside the cell.
Saturation phenomenon is the idea that the maximum velocity has been reached when all of the binding sites of transporter proteins are occupied.
Phospholipids are polar lipids, meaning that they contain molecules that react with water, such as nitrogen and oxygen. The basic structure is a glycerol backbone with 2 fatty acid chains plus a phosphate group. There will be another group attached to the phosphate group, known as the head group, which allows for classification of that specific phospholipid.
Phospholipids are distinct in that they contain a polar head and a hydrophobic tail in the same molecule. Because of this they are called ampipathic molecules. The head is hydrophillic (likes to react with water) and the tail is hydrophobic, or immiscible (does not like to react with water). This allows them to form a structural bilayer in the cell membrane. The hydrophyllic ends face outward while the hydrophobic ends remain inward. Lecithin is the major phospholipid found in the membrane. It can be synthesized in the body, but is also found in foods such as liver, egg yolk, and soybeans. Lecithin is an effective emulsifier.
Phospholipids are also found in lipoproteins, which are the transport vehicles for lipid in the blood. Lipids need help being transported because they are water immiscible. Therefore, they are hidden inside the lipoproteins. The hydrophyllic part of the phospholipid faces outward from the surface of the lipoprotein to allow it to freely move through the blood.
There are several types of lipoproteins: chylomicrons, which are made in the intestine; VLDL, which is made in the intestine and liver; LDL, which is made from VLDL in the blood; and HDL, which is made in the intestine and liver. The density depends upon the amount of protein and fat. A chylomicron has the highest amount of fat and the lowest protein, so it is the lowest density. HDL is the highest density due to its high protein content relative to fat.
Subscribe to:
Posts (Atom)
