Generic Lipid Metabolism

12 Mar

Lipid Metabolism

The human body carefully regulates how much energy it wants to generate. Therefore, unfortunately or fortunately, unlimited amount of glucose do not equate in unlimited ATP synthesis. Rising intracellular ATP concentrations eventually inhibit glucose catabolism and initiate glucose storage as glycogen or fat. Due to preference, the cells are able to store more fat than glycogen. Thus, fat accounts for 80-85% of stored energy.

Fats contain very little water, and yield more energy from catabolism than proteins or glucose. Products of fat digestion are transported in lymph in the form of protein enclosed free fatty acid (FFA) droplets called chylomicrons.

Triglyceride Oxidation: Glycerol and Free Fatty Acid Chains

Of the various lipids, only triglycerides (TG) are routinely oxidized for energy. The catabolism of triglycerides results in two different building blocks: glycerol and free fatty acid chains. Glycerol gets converted to glyceraldehyde phosphate and enters the glycolytic pathway. (However, glyceraldehyde phosphate produces about half the energy that a simple glucose can produce.)

Meanwhile, triglycerides undergo beta-oxidation in the mitochondrion. Beta-oxidation refers to the oxidation of the carbon in the beta (third carbon) position during the process and cleavage of the fatty acid in each case occurs between alpha and beta carbons. The fatty acid chains are broken apart into 2-carbon acetic acid fragments (while, the FAD and NAD+ coenzymes get reduced). Coenzyme A gets fused with the acetic acid to form acetyl CoA which is a known starting material that the oxaloacetic acid picks up to begin the Krebs cycle. Acetyl CoA resulting from beta-oxidation of fatty acids cannot be used for gluconeogenesis because the process is irreversible (unlike glycerol subunit that directly enters the glycolysis).

Lipogenesis

Lipogenesis is the process of triglyceride synthesis. It occurs when the cellular ATP and glucose levels are high. (Excess ATP also leads to an accumulation of acetyl CoA that would otherwise enter citric acid cycle.) Glycerol and free fatty acid chains are recombined and stored for later usage. The accumulation of fatty tissue changes on the regular; and it is not of the same composition as it was a month ago.

Acetyl CoA molecules are condensed together. They form fatty acid chains, 2 carbons at a time. (Hence, why most of the fatty acids contain an even number of carbon atoms.) If you remember, acetyl CoA is an intermediate in glucose oxidation after the glycolytic pathway. Therefore, since the acetyl CoA is the starting material for fatty acid synthesis, glucose can be easily converted to fat. A diet poor in fat can utilise carbohydrates to provide all of the raw materials needed to form triglycerides. (High blood sugar results in lipogenesis as the major activity in liver and in adipose tissues.)

Lipolysis

The liver, cardiac muscle, and resting skeletal muscles actually prefer fatty acids as an energy source. Lipolysis is the breakdown of triglycerides into glycerol and free fatty acid chains. When carbohydrate intake is inadequate, lipolysis is accelerated as the body adjusts to fill the energy requirements from lipids. However, there is a limiting factor: oxaloacetic acid. The ability of oxaloacetic acid to act as a pick-up molecule is crucial for the acetyl CoA to enter the Krebs cycle. When there is a lack of glucose, oxaloacetic acid gets converted into glucose to be used as energy for brain functions. Without the oxaloacetic acid to act as a pickup molecule, acetyl CoA accumulates in the mitochondrion. However, the body has an adaptive response: ketogenesis. During ketogenesis, the liver converts the excess of acetyl CoA into ketone bodies, or ketones, which are then released to blood. (Ketone bodies, such as: acetoacetic acid, β-hydroxybutyric acid, and acetone.)

Acetyl CoA can be further processed into cholesterol in the liver; and the liver can use the cholesterol to form bile salts. The ovaries, testes, and adrenal cortex can use cholesterol to synthesise their respective steroid hormones.

So, what can be the problem with utilising ketone bodies? Ketone bodies are mostly organic acids, thereby lead to a decrease of blood pH. An accumulation of ketones in the blood is termed ketosis. Ketosis is a consequence of starvation, unwise dieting, and diabetes mellitus. It can lead to severe consequences and thus need to be looked into else where.

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