LIPID SYNTHESIS

Fatty acids are built from 2-C units exported from the mitochondria as citrate: citrate ® OAA + acetyl-CoA This occurs in high-energy conditions, when isocitrate dehydrogenase is inhibited by NADH, ATP. The OAA is reduced to malate and recycled into the mitochondria.

(enzyme-biotin-CO2 intermediate)

O || R-CH2-CH2-CH2-C-S-ACP malonyl-S-ACP NADP+ O || R-CH2-C-S-ACP ﾟ CO2 HS-ACP NADPH O O || || R-CH2-C- CH2-C-S-ACP ﾟ H O | || R-CH2-C=C-C-S-ACP | H NADPH H2 O NADP+ OH O | || R-CH2-C- CH2-C-S-ACP | H

R-C(=O)-ACP or R-C(=O)-CoA ACP or CoA 1-acyl-glycerol-3-P triacylglycerol CoA Pi phosphatidyl-choline or -ethanolamine CDP-choline or CDP-ethanolamine CMP Phosphatidic acid Glycerol-3-P R-C(=O)-CoA

Control of FA synthesis in the cytoplasm occurs at acetyl-CoA carboxylase

Summary Fatty acids are synthesized in the cytoplasm, using acetyl-CoA exported from mitochondria (as citrate). The synthesis of fatty acids follows a “ß-reduction” cycle. Fatty acids are combined with glycerol-3-P to form triglycerides and phospholipids.

R-C(=O)-ACP or R-C(=O)-CoA ACP or CoA Glycerol-3-P 1-acyl-glycerol-3-P R-C(=O)-ACP or R-C(=O)-CoA H2O ACP or CoA Phosphatidic acid Pi R-C(=O)-CoA Diacylglycerol CoA Triacylglycerol

R-C(=O)-ACP or R-C(=O)-CoA ACP or CoA Glycerol-3-P 1-acyl-glycerol-3-P R-C(=O)-ACP or R-C(=O)-CoA CTP ACP or CoA PPi Phosphatidic acid inositol CDP-choline or CDP-ethanolamine CDP-diacylglycerol CMP CMP phosphatidyl-inositol phosphatidyl-choline or -ethanolamine