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Chapter: Biochemistry: The Citric Acid Cycle

Why Is It So Hard to Lose Weight?

One of the great tragedies about being human is that it is far too easy to gain weight and far too difficult to lose it.

Why Is It So Hard to Lose Weight?

One of the great tragedies about being human is that it is far too easy to gain weight and far too difficult to lose it. If we had to analyze the specific chemical reactions that make this a reality, we would look very carefully at the citric acid cycle, especially the decarboxylation reactions.

As everybody knows, all food in excess can be stored as fat. This is true for carbohydrates, proteins, and, of course, fats. In addition, these molecules can be interconverted, with the excep-tion that fats cannot give a net yield of carbohydrates. Why can fats not yield carbohydrates? The real answer lies in the fact that the only way a fat molecule would have to make glucose would be to enter the citric acid cycle as acetyl-CoA and then to be drawn off as oxaloacetate for gluconeogenesis. Unfortunately, the two carbons that enter are effectively lost by the decarboxylations. (We have already seen that, in one round of the citric acid cycle, it isn’t really these same two carbons that are lost; nevertheless, a two-carbon loss is a two-carbon loss, regard-less of which two carbons they were.) This leads to an imbalance in the catabolic pathways versus the anabolic pathways.

All roads lead to fat, but fat cannot lead back to carbohydrate. Humans are very sensitive to glucose levels in the blood because so much of our metabolism is geared toward protecting our brain cells, which prefer glucose as a fuel. If we eat more carbohydrates than we need, the excess carbohydrates turn to fat. As we know, it is very easy to put on fat, especially as we age. What about the reverse? Why don’t we just stop eating? Won’t that reverse the process? The answer is yes and no. When we start eating less, fat stores are mobilized for energy. Fat is an excellent source of energy because it forms acetyl-CoA and gives a steady influx for the citric acid cycle. Thus, we can lose some weight by reducing our caloric intake. Unfortunately, our blood sugar also drops as soon as our glycogen stores run out. We don’t have very much stored glycogen that could maintain our blood glucose levels.

After the blood glucose drops, we become depressed, slug-gish, and irritable. We start having negative thoughts like, “This dieting thing is really stupid. I should eat a pint of ice cream.” If we continue the diet, and given that we cannot turn fats into car-bohydrates, where does the blood glucose come from? Only one source remains: proteins. Proteins are degraded to amino acids, and they are eventually converted to pyruvate for gluconeogen-esis. Thus, we begin to lose muscle as well as fat.

There is a bright side to all of this, however. Using our knowl-edge of biochemistry, we can see that there is a better way to lose weight than dieting—exercise! If you exercise correctly, you can train your body to use fats to supply acetyl-CoA for the citric acid cycle. If you maintain a normal diet, you maintain your blood glucose and do not degrade proteins for that purpose; your ingested carbohydrates are sufficient to maintain blood glucose and carbohydrate stores. With the proper balance of exercise to food intake, and the proper balance of the right types of nutri-ents, we can increase the breakdown of fat without sacrificing our carbohydrate stores or our proteins. In essence, it is easier and healthier to train off the weight than to diet off the weight. This has been known for a long time. Now we are in a position to see why it is biochemically so.

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Biochemistry: The Citric Acid Cycle : Why Is It So Hard to Lose Weight? |

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