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Its acetyl-coenzyme A form is the primary input in the citric acid cycle and is obtained from glycolysis, amino acid metabolism, and fatty acid beta oxidation. This process is the body's primary catabolic pathway and is essential in breaking down the building blocks of the cell such as carbohydrates , amino acids , and lipids .
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 .
The acetyl group is removed by one of the HDAC enzymes during deacetylation, allowing histones to interact with DNA more tightly to form compacted nucleosome assembly. This increase in the rigid structure prevents the incorporation of transcriptional machinery, effectively silencing gene transcription.
Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. [1] Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and this complex links the glycolysis metabolic pathway to the citric acid cycle. Pyruvate ...
Acetyl-CoA synthetase (ACS) or Acetate—CoA ligase is an enzyme (EC 6.2.1.1) involved in metabolism of acetate. It is in the ligase class of enzymes, meaning that it catalyzes the formation of a new chemical bond between two large molecules.
This four step process repeats until acyl-CoA has removed all carbons from the chain, leaving only Acetyl-CoA. During one cycle of beta oxidation, Acyl-CoA creates one molecule of Acetyl-CoA, FADH2, and NADH. [7] Acetyl-CoA is then used in the citric acid cycle while FADH2 and NADH are sent to the electron transport chain. [8]
Metabolic production of acetyl-CoA is linked to histone acetylation and gene regulation. In mouse neurons, Mews et al. [7] identified a major role for the ACSS2 pathway to regulate histone acetylation and neuronal gene expression. Histone acetylation in mature neurons is associated strongly with memory formation.
Two specific enzymes participate on the carbon monoxide side of the pathway: CO dehydrogenase and acetyl-CoA synthase. The former catalyzes the reduction of the CO 2 and the latter combines the resulting CO with a methyl group to give acetyl-CoA. [2] [1] [3] Some anaerobic bacteria use the Wood–Ljungdahl pathway in reverse to break down acetate.