Biochemistry

TLO: Discuss the fate, metabolism, and functions of lipids.

The Fate of Lipids

Lipids, like carbohydrates, may be oxidized to produce ATP. If the body has no immediate need to use lipids in this way, they are stored in adipose tissue (fat depots) throughout the body and in the liver. A few lipids are used as structural molecules or to synthesize other essential substances. Some examples include phospholipids, which are constituents of plasma membranes; lipoproteins, which are used to transport cholesterol throughout the body; thromboplastin, which is needed for blood clotting; and myelin sheaths, which speed up nerve impulse conduction. Two essential fatty acids that the body cannot synthesize are linoleic acid and linolenic acid. Dietary sources include vegetable oils and leafy vegetables. The various functions of lipids in the body may be reviewed in table below. 

Triglyceride storage

A major function of adipose tissue is to remove triglycerides from chylomicrons and VLDLs and store them until they are needed for ATP production in other parts of the body. Triglycerides stored in adipose tissue constitute 98% of all body energy reserves. They are stored more readily than glycogen, in part because triglycerides are hydrophobic and do not exert osmotic pressure on cell membranes. Adipose tissue also insulates and protects various parts of the body.

Adipocytes in the subcutaneous layer contain about 50% of the stored triglycerides. Other adipose tissues account for the other half: about 12% around the kidneys, 10–15% in the omentum, 15% in genital areas, 5–8% between muscles, and 5% behind the eyes, in the sulci of the heart, and attached to the outside of the large intestine. Triglycerides in adipose tissue are continually broken down and resynthesized.  Thus, the triglycerides stored in adipose tissue today are not the same molecules that were present last month because they are continually released from storage, transported in the blood, and redeposited in other adipose tissue cells.

Lipid catabolism: Lipolysis

In order for muscle, liver, and adipose tissue to oxidize the fatty acids derived from triglycerides to produce ATP, the triglycerides must first be split into glycerol and fatty acids, a process called lipolysis. Lipolysis is catalysed by enzymes called lipases. Epinephrine and norepinephrine enhance triglyceride breakdown into fatty acids and glycerol. These hormones are released when sympathetic tone increases, as occurs, for example, during exercise.

Other lipolytic hormones include cortisol, thyroid hormones, and insulin-like growth factors. By contrast, insulin inhibits lipolysis. The glycerol and fatty acids that result from lipolysis are catabolized via different pathways. Glycerol is converted by many cells of the body to glyceraldehyde 3-phosphate, one of the compounds also formed during the catabolism of glucose. If ATP supply in a cell is high, glyceraldehyde 3-phosphate is converted into glucose, an example of gluconeogenesis. If ATP supply in a cell is low, glyceraldehyde 3-phosphate enters the catabolic pathway to pyruvic acid.

Fatty acids are catabolized differently than glycerol and yield more ATP. The first stage in fatty acid catabolism is a series of reactions, collectively called beta oxidation, that occurs in the matrix of mitochondria. Enzymes remove two carbon atoms at a time from the long chain of carbon atoms composing a fatty acid and attach the resulting two-carbon fragment to coenzyme A, forming acetyl CoA. Then, acetyl CoA enters the Krebs cycle. A 16-carbon fatty acid such as palmitic acid can yield as many as 129 ATPs on its complete oxidation via beta oxidation, the Krebs cycle, and the electron transport chain.

As part of normal fatty acid catabolism, hepatocytes can take two acetyl CoA molecules at a time and condense them to form acetoacetic acid. This reaction liberates the bulky CoA portion, which cannot diff use out of cells. Some acetoacetic acid is converted into beta-hydroxybutyric acid and acetone. The formation of these three substances, collectively known as ketone bodies, is called ketogenesis. Because ketone bodies freely diff use through plasma membranes, they leave hepatocytes and enter the bloodstream.

Other cells take up acetoacetic acid and attach its four carbons to two coenzyme A molecules to form two acetyl CoA molecules, which can then enter the Krebs cycle for oxidation. Heart muscle and the cortex (outer part) of the kidneys use acetoacetic acid in preference to glucose for generating ATP. Hepatocytes, which make acetoacetic acid, cannot use it for ATP production because they lack the enzyme that transfers acetoacetic acid back to coenzyme A.

Lipid anabolism: Lipogenesis

Liver cells and adipose cells can synthesize lipids from glucose or amino acids through lipogenesis, which is stimulated by insulin. Lipogenesis occurs when individuals consume more calories than are needed to satisfy their ATP needs. Excess dietary carbohydrates and fats all have the same fate—they are converted into triglycerides. Certain amino acids can undergo the following reactions: amino acids → acetyl CoA → fatty acids → triglycerides. The use of glucose to form lipids takes place via two pathways: (1) glucose → glyceraldehyde 3-phosphate → glycerol and (2) glucose → glyceraldehyde 3-phosphate→ acetyl CoA → fatty acids. The resulting glycerol and fatty acids can undergo anabolic reactions to become stored triglycerides, or they can go through a series of anabolic reactions to produce other lipids such as lipoproteins, phospholipids, and cholesterol.

 Watch this video to help you understand better about lipid metabolism.