Acetyl coenzyme acetylcholine synthesis

Acetylcholine synthesis and neurotransmission requires normal functioning of two active transport mechanisms. Choline acetyltransferase (ChAT) is the enzyme responsible for ACh synthesis from the precursor molecules acetyl coenzyme A and choline. ChAT is the neurochemical phenotype used to define cholinergic neurons although ChAT is present in cell bodies, it is concentrated in cholinergic terminals. The ability of ChAT to produce ACh is critically dependent on an adequate level of choline. Cholinergic neurons possess a high-affinity choline uptake mechanism referred to as the choline transporter (ChT in Fig. 5.1). The choline transporter can be blocked by the molecule hemicholinium-3. Blockade of the choline transporter by hemicholinium-3 decreases ACh release,... 

Figure 2.14 Iriter-relationship between intermediary. metabolism of glucose, phospholipids and acetylcholine synthesis. Acetyl CoA acetyl coenzyme A CAT-catechol-O-methyltransferase AChE acetylcholinesterase.

Acetylcholine synthesis. Acetylcholine (ACh) is a prominent neurotransmitter, which is formed in cholinergic neurons from two precursors, choline and acetyl coenzyme A (AcCoA) (Fig. 12—8). Choline is derived from dietary and intraneuronal sources, and AcCoA is synthesized from glucose in the mitochondria of the neuron. These two substrates interact with the synthetic enzyme choline acetyltransferase to produce the neurotransmitter ACh. 

Acetylcholine is synthesized by the transfer of the acetyl group from its activated acetyl coenzyme A form to the aminoalcohol choline (Eq. 8.1). The enzyme, ChAT, is not actually highly substrate-specific and can acetylate other basic alcohols or transfer acyl groups other than acetyl. The rate of synthesis can be as high as 4,000 (ig/g of tissue per hour. 

Jope, R. S. (1979). High affinity choline transport and acetyl coenzyme A production and their roles in the regulation of acetylcholine synthesis. Brain Res. Rev., 1, 313-44. 

Several pantothenic acid analogs inhibit those reactions that require coenzyme A (acetylation of sulfanilamide and acetylcholine synthesis). Among these anti-... 

The metabolic functions of pantothenic acid in human biochemistry are mediated through the synthesis of CoA. Pantothenic acid is a structural component of CoA. which is necessary for many important metabolic processes. Pantothenic acid is incorporated into CoA by a. series of five enzyme-catalyzed reactions. CoA is involved in the activation of fatty acids before oxidation, which requires ATP to form the respective fatty ocyl-CoA derivatives. Pantothenic acid aI.so participates in fatty acid oxidation in the final step, forming acetyl-CoA. Acetyl-CoA is also formed from pyruvate decarboxylation, in which CoA participates with thiamine pyrophosphate and lipoic acid, two other important coenzymes. Thiamine pyrophosphate is the actual decarboxylating coenzyme that functions with lipoic acid to form acetyidihydrolipoic acid from pyruvate decarboxylation. CoA then accepts the acetyl group from acetyidihydrolipoic acid to form acetyl-CoA. Acetyl-CoA is an acetyl donor in many processes and is the precursor in important biosyntheses (e.g.. those of fatty acids, steroids, porphyrins, and acetylcholine). 

Coenzyme A was discovered by Lipmann in 1945 as necessary for the acetylation of sulfanilamide by pigeon liver extracts. Shortly thereafter this same coenzyme was identified as the activator of choline acetylation earlier observed by Nachmansohn and Berman, as well as Feldberg and Mann. Subsequently, work from Lipmann s laboratory, as well as from other laboratories, extended the role of CoA to a large variety of transacetylation reactions, i.e., acetylation of aromatic amines, synthesis of acetylcholine, of citrate, of acetoacetate, of fatty acids, of sterols, and of phospholipids. ... 

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