Biochemistry in Tables, Schemes, and Graphs - S.D. Zhamsaranova 2009

Lipid Metabolism and Functions
Biosynthesis of Fatty Acids

The process takes place in various compartments of The Cell. Saturated Fatty acids with a carbon chain of up to C16 (palmitate) are synthesized in the Cytoplasm.

The substrate for fatty acid synthesis is acetyl-CoA, which is produced by the Oxidation of Pyruvate. The utilization of pyruvate for palmitate synthesis involves the following metabolic pathways:

- The oxidation of glucose via Glycolysis to pyruvate in the Cytosol,

- The oxidative decarboxylation of pyruvate in the Mitochondria, followed by the Condensation of acetyl-CoA with oxaloacetate to yield citrate.

Citrate is then transported into the cytosol, where it breaks down into acetyl-CoA and oxaloacetate. Several mechanisms exist for The transport of acetyl-CoA from the mitochondria into the cytoplasm.

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A prerequisite for the export of acetyl-CoA from the mitochondria into the cytoplasm is an adequate supply of ATP within the cell. If cellular ATP levels are low, acetyl-CoA is instead degraded to СО₂ and Н₂О.

The initial reaction in FATTY ACID Biosynthesis is the carboxylation of acetyl-CoA to form malonyl-CoA. This reaction is catalyzed by acetyl-CoA carboxylase, which utilizes biotin as a coenzyme. This is followed by repeating cycles consisting of six reactions.

The entire process is catalyzed by palmityl synthetase, a multifunctional protein enzyme consisting of a single polypeptide chain folded into two domains.

FATTY ACID SYNTHESIS REACTIONS.

Each subsequent synthesis cycle begins with the attachment of a new malonyl-CoA molecule to one of the SH-groups located in the active sites of the domains.

Each cycle extends the carbon chain by two carbon atoms. Once the chain reaches a length of 16 carbon atoms, the thioester bond undergoes Hydrolysis, releasing free palmitate.

The overall equation for palmitate synthesis (7 cycles): Ацетил-СоА + 7Малонил-КоА + 14(NADРН + Н⁺) → пальмитат + 8HS-CoA + 7 СO₂ + 14NADP⁺ + 7H₂O

Further chain elongation occurs in the mitochondria, whereas in The Endoplasmic reticulum, saturated Fatty acids are converted into unsaturated ones, and chain elongation also takes place.