Acetyl coenzyme A or Acetyl – CoA is depicted to be a molecule that effectively participates in many biochemical reactions such as protein, lipid metabolism as well as carbohydrates. The main function of this coenzyme is to deliver the acetyl group into the citric acid cycle that is needed to be oxidized regarding the production of energy. The Coenzyme A mainly consists of a group that consists of β-mercaptoethylamine which is mainly linked with the vitamin pantothenic acid via an amide linkage as well as with 3'-phosphorylated ADP. The acetyl group present in an acetyl-CoA is linked with the sulfhydryl substituent regarding the group of β-mercaptoethylamine. This thioester linkage or bondage is stated to be a very high energy bond that is observed to be reactive.
CoA is acetylated to the acetyl-CoA via following the procedure of breaking down of carbohydrates via glycolysis. Moreover this also happens with the breakdown of the fatty acids via the procedure of β-oxidation. After this procedure the acetyl-CoA enters into the cycle of citric acid and here the acetyl group gets oxidized further to CO2 and H2O. Thus the energy then released is captured regarding the formation of 11 ATP and a single individual GTP per group of acetyl.
The synthesis of the acetyl coenzyme A is specially determined by the sources of the carbon. There are basically two procedures involved with the synthesis. These are briefly stated as follows:
Extramitochondrial: When the glucose levels are very high then the procedure of glycolysis takes place in a rapid manner which further increases the quantity of citrate which is produced from the tricarboxylic acid cycle. After this the citrate is exported to the other organelles that are present outside the mitochondria tends to break into the acetyl-CoA as well as oxaloacetate by the enzyme of ATP citrate lyase. Whereas, when the glucose levels are low the CoA is acetylated by the help of acetate through the procedure of the acetyl-CoA synthetase also coupled with the ATP hydrolysis. In this process ethanol tends to serve as a carbon source regarding the acetylation of CoA that further utilizes the enzyme of alcohol dehydrogenase.
Intramitochondrial: When the glucose levels are high the acetyl CoA is produced by the procedure of glycolysis. Pyruvate undergoes the oxidative decarboxylation that loses the carboxyl group to create the acetyl-CoA, providing off 33.5 kJ/mol of energy. Moreover, when the glucose levels are low then the production of the acetyl-CoA is linked with the β-oxidation regarding the fatty acids. These fatty acids are firstly converted to the acyl-CoA. After this the acyl-CoA is degraded into a four step cycle that consists of oxidation, hydration, oxidation and thiolysis. These cycle is involved with the production of the new fatty acid chains with two fewer carbons as well as acetyl-CoA as a by-product.
The acetyl-CoA is mainly synthesized within the mitochondria by a number of reactions: oxidative decarboxylation of pyruvate; catabolism of some amino acids and β-oxidation of fatty acids. Since the acetyl-CoA cannot be transported directly across the inner mitochondrial membrane to the cytosol the carbon atoms are transferred by the two transport mechanisms that are stated below:
Transport dependent on carnitine: Carnitine specifically participates within the transport of the long-chain acyl-CoA into the mitochondria as well as plays a similar significant role regarding the transport of acetyl-CoA to the outer side of the mitochondria. However, the carnitine acetyl transfer have a very minor role in acetyl-CoA transport.
Cytosolic generation of acetyl-CoA: The Citrate is synthesized from the oxaloacetate and the acetyl-CoA is transported from the mitochondria into the cytosol through the tricarboxylate anion carrier system as well as cleaved for yielding the acetyl-CoA and the oxaloacetate.
Moreover it can be said that the Acetyl-CoA significantly represents a single key node within metabolism because of its intersection with the overall metabolic pathways as well as transformations. The emergence of the evidence reveals that the cells monitor the enhanced levels of the acetyl-CoA as a key indicator of their metabolic state, through distinctive protein acetylation modifications that are dependent on this metabolite. The high nucleocytosolic acetyl-CoA amounts are a signature of the “growth” state thus promoting its utilization for the lipid synthesis as well as histone acetylation. However, fluctuations in acetyl-CoA within the subcellular compartments enables the substrate-level to regulate regarding the acetylation modifications, henceforth also necessitates the significant function of the sirtuin deacetylases for catalysing the removal of the spontaneous modifications which might not be intentional.
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