Acetyl-CoA metabolism

Acetyl-CoA is the universal donor of acetyl groups for acetylation reactions, and alsotakes part in tricarboxylic acids cyclewith the help of glyoxylate cycle. This process is important for the synthesis of carbohydrates.

Inclusion of acetyl-CoA in tricarboxylic acid cycle (Krebs cycle) depends on the availability of oxaloacetate. When starving or having diabetes oxaloacetate is spent for the glucose formation. Under such conditions ketone bodies are formed from acetyl-CoA.

Ketone bodiesareacetoacetate СН₃СОСН₂СООН, β-hydroxybutyrate СН₃СНОНСН₂СООН and acetone СН₃СОСН₃. Ketone bodies are formed in liver. In healthy person's blood ketone bodies are present in very small concentration, in the case of pathologies their amount increases.

Liver serves as the basic place of acetoacetate and 3-hydrooxibutyrate formation. The heart muscle and the kidney cortex preferably use acetoacetate as their "fuel" instead of glucose. Contrary to it, glucose is the main "fuel" for brain of people receiving balanced nutrition. When starving and having diabetes the brain adapts for acetoacetate use.

In peripheric tissues 3-hydrooxibutyrate is capable of being oxidized to acetoacetate, and further to acetyl-CoA.

In blood of a healthy person ketone bodies are very few (in blood serum it is 0,03-0,2 mmol/l). In pathological conditions (persons with the heavy form of diabetes, starvation) concentration of ketone bodies in blood can reach 16-20 mmol/l. Ketonemia is usually accompanied by ketonuria.

Lipogenesis

Lipogenesisis biosynthesis of fatty acids de novo.

1. Carboxylation of acetyl-CoA and formation of malonyl-CoA. Enzyme is Acetyl CoA carboxylase, it contains biotin.

СО₂ + АТP + biotin-enzyme ® carboxybiotin-enzyme + АDP + P_i

+ biotin-enzyme

The multienzyme complex which is called synthetase (synthase) of fatty acids consists of 6 enzymes bound with acyl carrier protein (ACP). It has two free HS-groups.

2. Bond of acetyl-CoA and malonyl-CoA with ACP.

3. Condensation of two acetyl residues is catalyzed byβ-ketoacyl ACP synthase.

4. Carbonyl group reduction.

5. Dehydration.

6. Hydrogenation. As a result butyryl-ACPis formed.

Further the reaction cycle repeats. At the last stage there is hydrolysis. The enzyme palmitoyl thioesterase separates palmitate from fatty acid synthase.

Sources of NADPH for the synthesis of fatty acids:about half is supplied by pentose phosphate pathway of glucose oxidation. The other half is formed due to the action of NADP-dependent malate dehydrogenase.

Palmitate is the end product of the reactions of fatty acid synthase system. It serves as the predecessor of other fatty acids of an organism. Elongation of carbon chain occurs with the help of the enzyme elongase. Unsaturated fatty acids are formed from saturated with the help of enzyme desaturаse.

Date: 2016-04-22; view: 1011