Acetyl choline coenzyme

In 1945 Lipmann found that a novel coenz3mae—coenzyme A— is required for the enzymic acetylation of sulfanilamide in pigeon liver preparations. Soon afterwards Nachmannsohn and Berman (see also ) found that a coenzyme is also required for the synthe of acetyl choline from choline and acetate in brain tissue, and this was found to be identical with the coenzyme of the acetylation of sulfanilamide, i Subsequently, three other reactions of acetate were found to involve coenzyme A the formation of acetoacetic acid from acetate, the s3mthesis of citrate from oxalacetate and acetate, - and the exchange reaction between acetyl phosphate and inorganic phosphate in bacterial extracts. " Thus, coenzyme A was shown to be a general coenzyme of acetylations, and... 

The neurotransmitter must be present in presynaptic nerve terminals and the precursors and enzymes necessary for its synthesis must be present in the neuron. For example, ACh is stored in vesicles specifically in cholinergic nerve terminals. It is synthesized from choline and acetyl-coenzyme A (acetyl-CoA) by the enzyme, choline acetyltransferase. Choline is taken up by a high affinity transporter specific to cholinergic nerve terminals. Choline uptake appears to be the rate-limiting step in ACh synthesis, and is regulated to keep pace with demands for the neurotransmitter. Dopamine [51 -61-6] (2) is synthesized from tyrosine by tyrosine hydroxylase, which converts tyrosine to L-dopa (3,4-dihydroxy-L-phenylalanine) (3), and dopa decarboxylase, which converts L-dopa to dopamine. 

Acetylcholine is the product of the reaction between choline and acetyl coenzyme A in the presence of choline acetylase (41). 

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 13.3. An overview of the chemical events at a cholinergic synapse and agents commonly used to alter cholinergic transmission acetyl CoA, acetyl coenzyme A Ch, choline. Nicotine and scopolamine bind to nicotinic and muscarinic receptors, respectively (nicotine is an agonist while scopolamine is an antagonist). Most anti-Alzheimer drugs inhibit the action of the enzyme cholinesterase.

Another observation on oxalate formation is that other a-keto acids, such as oxalosuccinic acid (74) and a-ketoglutaric acid (106) do not seem to yield oxalate directly but indirectly (123). This appears to be due to the fact that only oxaloacetic acid can function as an acetate donor. In this connection the intervention of Coenzyme A may be considered, since it is reported to function in the acetylation of sulfanilamide and choline (73) and recently was shown to take part in the enzymatic synthesis of citric acid. This concept may be illustrated as follows ... 

Brain ChAT has a KD for choline of approximately 1 mmol/1 and for acetyl coenzyme A (CoA) of approximately 10pmol/l. The activity of the isolated enzyme, assayed in the presence of optimal concentrations of cofactors and substrates, appears far greater than the rate at which choline is converted to ACh in vivo. This suggests that the activity of ChAT is repressed in vivo. Surprisingly, inhibitors of ChAT do not decrease ACh synthesis when used in vivo this may reflect a failure to achieve a sufficient local concentration of inhibitor, but also suggests that this step is not rate-limiting in the synthesis of ACh [18-20]. 

This enzyme [EC 2.3.1.6], also known as choline ace-tylase, catalyzes the reaction of acetyl-CoA with choline to produce coenzyme A and O-acetylcholine. The enzyme can also utilize propionyl-CoA as a substrate, albeit as a weaker reactant. 

It is synthesized within the cholinergic neurons by the transfer of an acetyl group from acetyl coenzyme A to the organic base choline. The specific enzyme choline acetylase is essential for this reaction. Coenzyme A is widely distributed in the body and choline acetylase is synthesized in the cell bodies of the cholinergic neurons. 

Acetylcholine is an ester composed of acetate (from acetyl coenzyme A) and choline (either synthesized de novo or taken in the diet as lecithin). The enzyme choline acetyl transferase catalyzes the reaction to form Ach. The breakdown of Ach back to acetate and choline, which will terminate its activity, is catalyzed by the enzyme acetylcholineesterase (Achase). 

CH3CSCoA + HOCH2CH2N(CH3)3 acetylase> CH3COCH2CH2N(CH3)3 + CoASH Acetyl coenzyme A Choline Acetylcholine Coenzyme A... 

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. 

The activation event Acetylcholine is synthesized from choline and acetyl coenzyme A (Acetyl-CoA) by the enzyme choline acetyltransferase (ChAT) and is immediately stored in small vesicular compartments closely attached to the cytoplasmic side of the presynaptic membranes. 

Acetylcholine is synthesized from acetyl coenzyme A (acetyl-CoA) and choline within the presynaptic terminal by the enzyme choline acetylase. The acetylcholine formed is stored in small, lightly staining synaptic vesicles that are concentrated around the synaptic contact area. The release of acetylcholine is calcium dependent. The entire content of a synaptic vesicle is released into the cleft in an all-or-none manner, where it interacts with its receptors and then is rapidly destroyed by acetylcholinesterase. Under normal circumstances, the half-life for acetylcholine in the synaptic cleft is about 1 ms. The acetylcholine is hydrolyzed to choline and acetate, and the choline is actively pumped back into the presynaptic terminal to be used to synthesize more acetylcholine. 

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