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Synthesis of saturated fatty acids via fatty acid synthase II in E. coli. Straight-chain fatty acid synthesis occurs via the six recurring reactions shown below, until the 16-carbon palmitic acid is produced. [2] [3] The diagrams presented show how fatty acids are synthesized in microorganisms and list the enzymes found in Escherichia coli. [2]
Fatty acid synthesis starts with acetyl-CoA and builds up by the addition of two-carbon units. Fatty acid synthesis occurs in the cytoplasm of cells while oxidative degradation occurs in the mitochondria. Many of the enzymes for the fatty acid synthesis are organized into a multienzyme complex called fatty acid synthase. [5]
Fatty acids are first converted to acyl-CoA. Acyl-CoA is then degraded in a four-step cycle of oxidation, hydration, oxidation and thiolysis catalyzed by four respective enzymes, namely acyl-CoA dehydrogenase, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and thiolase. The cycle produces a new fatty acid chain with two fewer carbons and ...
Long chain fatty acids (more than 14 carbon) need to be converted to fatty acyl-CoA in order to pass across the mitochondria membrane. [6] Fatty acid catabolism begins in the cytoplasm of cells as acyl-CoA synthetase uses the energy from cleavage of an ATP to catalyze the addition of coenzyme A to the fatty acid. [6]
Once the fatty acid is inside the mitochondrial matrix, beta-oxidation occurs by cleaving two carbons every cycle to form acetyl-CoA. The process consists of 4 steps. [2] A long-chain fatty acid is dehydrogenated to create a trans double bond between C2 and C3.
The cytosolic acetyl-CoA is carboxylated by acetyl-CoA carboxylase into malonyl-CoA, the first committed step in the synthesis of fatty acids. [19] [20] Malonyl-CoA is then involved in a repeating series of reactions that lengthens the growing fatty acid chain by two carbons at a time.
Cytosolic citrate, meaning citrate in the cytosol, is a key substrate for the generation of energy. It releases acetyl-CoA and provides NADPH for fatty acid synthesis, and, in subsequent pathways, generates NAD + for glycolysis. Citrate also activates acetyl-CoA carboxylase, an enzyme that is essential in the fatty acid synthesis pathway. [11]
Schematic diagram of the acetate biosynthetic pathway [1] The acetate pathway, also known as the polyketide pathway, is a fundamental biosynthetic route in organisms for the production of fatty acids and polyketides. This pathway operates at the interface of central metabolism and specialized metabolite synthesis, playing a crucial role in the ...