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The synthesis of even-chained fatty acid synthesis is done by assembling acetyl-CoA precursors, however, propionyl-CoA instead of acetyl-CoA is used as the primer for the biosynthesis of long-chain fatty acids with an odd number of carbon atoms. [19] Regulation. In B. subtilis, this pathway is regulated by a two-component system: DesK and DesR.
The cytosolic acetyl-CoA can also condense with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA which is the rate-limiting step controlling the synthesis of cholesterol. [16] Cholesterol can be used as is, as a structural component of cellular membranes, or it can be used to synthesize steroid hormones , bile salts , and vitamin D .
Synthesis within the body starts with the mevalonate pathway where two molecules of acetyl CoA condense to form acetoacetyl-CoA. This is followed by a second condensation between acetyl CoA and acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl CoA . [38] This molecule is then reduced to mevalonate by the enzyme HMG-CoA reductase.
However, this acetyl CoA needs to be transported into cytosol where the synthesis of fatty acids occurs. This cannot occur directly. To obtain cytosolic acetyl-CoA, citrate (produced by the condensation of acetyl-CoA with oxaloacetate) is removed from the citric acid cycle and carried across the inner mitochondrial membrane into the cytosol. [18]
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]
The starting material is acetyl-CoA. It is a molecule that is involved in ATP synthesis, protein metabolism, and lipid metabolism. [6] As the inner membrane is not permeable to this molecule, acetyl-CoA needs to be converted into other products for effective transport. [7] It is also the first step of the reaction.
The process of beta oxidation requires the following enzymes: acyl-CoA dehydrogenase, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase. [15] The diagram to the left shows how fatty acids are converted into acetyl-CoA. The overall net reaction, using palmitoyl-CoA (16:0) as a model substrate is:
This pathway operates at the interface of central metabolism and specialized metabolite synthesis, playing a crucial role in the synthesis of both primary and secondary metabolites. [ 2 ] [ 3 ] [ 1 ] It begins with acetyl-CoA and involves the stepwise condensation of two-carbon units, typically derived from malonyl-CoA , to form increasingly ...