1.4. Lipogenesis
Lipogenesis is 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 + Pi
c
malonyl-CoA
+ 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 by β-ketoacyl ACP synthase.
4. Carbonyl group reduction.
5. Dehydration.
6. Hydrogenation. As a result butyryl-ACP is formed.
Further the reaction cycle repeats. At the last stage there is hydrolysis. The enzyme palmitoyl thioesterase separates palmitate from fatty acid synthase.
Deacylase
Palmitoil-ACP
Palmitic
acid
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.
Regulation of fatty acids synthesis and break down
Switching of processes of fatty acids synthesis to their oxidation occurs during the change of periods of digestion to postabsorbtive state and is carried out with the help of regulatory mechanisms.
The major element of fat acids synthesis regulation is acetyl-CoA carboxylase. During digestion the concentration of a citrate increases in cytosol and it is a transmitting agent of the acetyl residues from mitochondria. Citrate is an allosteric activator of acetyl-CoA-carboxylase. Synthesis of malonyl-CoA and, hence, fatty acids synthesis is accelerated. The end product palmityl-CoA is the inhibitor of acetyl-CoA-carboxylase.
Activity of acetyl-CoA-carboxylase is controlled by glucagon and adrenaline by means of adenylatecyclase system. The phosphorylated form of enzymet is inactive, dephosphorylated form is active. These hormones also change the state of lipase in adipose tissue into active by phosphorylation. Hence, fatty acids synthesis is stopped, and TAG mobilisation, fatty acids oxidation and ketone bodies synthesis begin.
Regulatory enzyme of β-oxidation is acylcarnitine transferase. Its allosteric inhibitor is malonyl-CoA. In postabsorbtive period when the reception of the acetyl residues from mitochondria into cytosol is stopped, synthesis of malonyl-CoA is stopped too, and β-oxidation is activated. β-oxidation is activated also during active use of АТP.
The rate of fatty acids biosynthesis is in many respects defined by the rate of formation of triglycerides and phospholipids.