Lipid Metabolism

Glycolysis &
Citric Acid Cycle
Protein Metabolism  Elmhurst College
Fatty Acid Spiral Reactions Acetyl CoA Fates Energy Summary  Chemistry Department
Overview, Summary Lipids Diabetes Reveiw Metabolism  Virtual ChemBook

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Acetyl CoA - Cross Roads Compound

Metabolic Fates of Acetyl CoA:

If you reflect on both the content lipid metabolism and the previous carbohydrate metabolism, you can appreciate that there is a special central role for acetyl CoA. Acetyl CoA acts both as a metabolic "receiving and shipping department" for all classes of biomolecules and as a major source of useful metabolic energy. The diagram on the left summarizes all metabolism and the central role of acetyl CoA. The diagram the next lower panel focuses on other functions as well.

The interactions of amino acids with acetyl CoA and the citric acid cycle will be studied in protein metabolism. Notice that acetyl CoA can react "reversibly" in the degradation or synthesis of lipids and amino acids. This is not the case with carbohydrate metabolism. In mammals, it is impossible to use acetyl CoA to make carbohydrates.

Synthesis of Cholesterol and other Steroids:

Without going into detail, acetyl CoA forms the basis from which the fairly complicated steroids are synthesized. Some steroids of importance include cholesterol, bile salts, sex hormones, aldosterone, and cortisol.

The major concern about cholesterol in the diet is muted somewhat by the knowledge that the liver can and does synthesize all of the cholesterol that the body needs. Excess cholesterol, whether from food or synthesized by the liver, ends up in the blood stream where it builds up on the artery walls. It has been determined that cholesterol levels can be controlled by lowering the amount of saturated fat and increasing the unsaturated fats. Unsaturated fats seem to speed the rate at which cholesterol breaks down in the blood. Controlling fats and cholesterol in the diet can significantly affect the levels of these substances in the blood.

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Since carbohydrates are the major part of the diet, they must be immediately converted into energy, stored as glycogen, or converted into fats. The introduction has already presented the facts about the necessity of storing energy as fat. A total of 55% of the carbohydrates are involved in the synthesis of fats.

The total energy content of the diet must be balanced with the energy requirements of the human body. If excess foods (calories) are ingested beyond the body's energy needs, the excess foods (energy) are converted into fat. If insufficient calories are ingested, the energy deficit is made up by oxidizing fat reserves. These simple facts provide the key to weight control although it is probably more easily understood than carried out in practice.

Excessive deposits of lipids lead to an obese condition. Extensive blood capillary networks in these deposits mean that they are quite active metabolically. Obesity puts a strain on the heart by causing it to pump blood through extra capillaries. Generally, obesity results from overeating, but a few people have malfunctioning endocrine glands.

Lipid metabolism is in a constant state of dynamic equilibrium. This means that some lipids are constantly being oxidized to meet energy needs, while others are being synthesized and stored. In rats, the average life-time of a single lipid molecule ranges from 2 to 10 days. A similar figure probably applies to human lipid metabolism.

The sequence of reactions involved in the formation of lipids is known as Lipogenesis. Lipogenesis is not simply the reverse of the fatty acid spiral, but does start with acetyl CoA and does build up by the addition of two carbons units. The synthesis occurs in the cytoplasm in contrast to the degradation (oxidation) which occurs in the mitochondria. Many of the enzymes for the fatty acid synthesis are organized into a multienzyme complex called fatty acid synthetase.

The major points in the overall lipogenesis reactions are:
1) ATP is required
2) The reactions are reductions (addition of H+ and use of NADPH) which are the reverse of the oxidations in the fatty acid spiral.

Link to: Fatty Acid Synthesis (move cursor over arrows)
Jim Hardy, Professor of Chemistry, The University of Akron.

Starvation and Diabetes - Synthesis of Ketone Bodies:

When the body is deprived of food whether by voluntary or involuntary fasting, starvation is the net result. During starvation, glycogen reserves are rapidly depleted and the body begins to metabolize reserves of fat and protein.

The entry of acetyl CoA into the citric acid cycle depends on the availability of oxaloacetic acid for the formation of citric acid. In starvation or uncontrolled diabetes situations, oxaloacetic acid is used to synthesize glucose and is then not available for use with acetyl CoA. Under these conditions, acetyl CoA is diverted from the citric acid cycle to the formation of acetoacetic and 3-hydroxybutanoic acids.

In three steps, two acetyl CoA react to make acetoacetic acid.

The acetoacetic acid may be changed into either acetone or
3-hydroxybutanoic acid.

All three compounds are collectively known as ketone bodies even though one is not a ketone.

The odor of acetone may be detected on the breath of a person with excess ketone bodies in the blood. The overall accumulation of ketone bodies in blood and urine is known as ketosis. The acids also upset buffers in the blood to cause acidosis.

Both acetoacetic acid and 3-hydroxybutanoic acid can be used by the heart, kidneys, and brain for metabolism to produce energy. The heart and kidneys actually prefer these to glucose. In contrast, the brain prefers glucose, but will adapt if necessary in starvation or diabetic conditions.

Link to: Ketone Bodies (move cursor over arrows)
Jim Hardy, Professor of Chemistry, The University of Akron.