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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 .
HMG-CoA synthase: Acetoacetyl-CoA condenses with another Acetyl-CoA molecule to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). HMG-CoA reductase: HMG-CoA is reduced to mevalonate by NADPH. This is the rate limiting step in cholesterol synthesis, which is why this enzyme is a good target for pharmaceuticals . mevalonate-5-kinase
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 and cholesterol 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 ...
Cholesterol can be made from acetyl-CoA through a multiple-step pathway known as isoprenoid pathway. Cholesterols are essential because they can be modified to form different hormones in the body such as progesterone. [6] 70% of cholesterol biosynthesis occurs in the cytosol of liver cells. [citation needed]
Besides its role in the synthesis of ketone bodies, HMG-CoA is also an intermediate in the synthesis of cholesterol, but the steps are compartmentalised. [1] [2] Ketogenesis occurs in the mitochondria, whereas cholesterol synthesis occurs in the cytosol, hence both processes are independently regulated. [2]
Acetoacetyl CoA is the precursor of HMG-CoA in the mevalonate pathway, which is essential for cholesterol biosynthesis. It also takes a similar role in the ketone bodies synthesis (ketogenesis) pathway of the liver. [1] In the ketone bodies digestion pathway (in the tissue), it is no longer associated with having HMG-CoA as a product or as a ...
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.