Enzymes choline acetyltransferase

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. Acetylcholiae (ACh) (1) is a crystalliae material that is very soluble ia water and alcohol. ACh, synthesized by the enzyme choline acetyltransferase (3), iateracts with two main classes of receptor ia mammals muscarinic (mAChR), defiaed oa the basis of the agonist activity of the alkaloid muscarine (4), and nicotinic (nAChR), based on the agonist activity of nicotine (5) (Table 1). m AChRs are GPCRs (21) n AChRs are LGICs (22). 

The reaction of choline with mitochondrial bound acetylcoenzyme A is catalysed by the cytoplasmic enzyme choline acetyltransferase (ChAT) (see Fig. 6.1). ChAT itelf is synthesised in the rough endoplasmic reticulum of the cell body and transported to the axon terminal. Although the precise location of the synthesis of ACh is uncertain most of that formed is stored in vesicles. It appears that while ChAT is not saturated with either acetyl-CoA or choline its synthesising activity is limited by the actual availability of choline, i.e. its uptake into the nerve terminal. No inhibitors of ChAT itself have been developed but the rate of synthesis of ACh can, however, be inhibited by drugs like hemicholinium or triethylcholine, which compete for choline uptake into the nerve. 

Acetylcholine is formed from acetyl CoA (produced as a byproduct of the citric acid and glycolytic pathways) and choline (component of membrane lipids) by the enzyme choline acetyltransferase (ChAT). Following release it is degraded in the extracellular space by the enzyme acetylcholinesterase (AChE) to acetate and choline. The formation of acetylcholine is limited by the intracellular concentration of choline, which is determined by the (re)uptake of choline into the nerve ending (Taylor Brown, 1994). 

Synthesis of noradrenaline (norepinephrine) is shown in Figure 4.7. This follows the same route as synthesis of adrenaline (epinephrine) but terminates at noradrenaline (norepinephrine) because parasympathetic neurones lack the phenylethanolamine-N-methyl transferase required to form adrenaline (epinephrine). Acetylcholine is synthesized from acetyl-Co A and choline by the enzyme choline acetyltransferase (CAT). Choline is made available for this reaction by uptake, via specific high-affinity transporters, within the axonal membrane. Following their synthesis, noradrenaline (norepinephrine) or acetylcholine are stored within vesicles. Release from the vesicle occurs when the incoming nerve impulse causes an influx of calcium ions resulting in exocytosis of the neurotransmitter. 

Schematic illustration of a generalized cholinergic junction (not to scale). Choline is transported into the presynaptic nerve terminal by a sodium-dependent choline transporter (CHT). This transporter can be inhibited by hemicholinium drugs. In the cytoplasm, acetylcholine is synthesized from choline and acetyl -A (AcCoA) by the enzyme choline acetyltransferase (ChAT). Acetylcholine is then transported into the storage vesicle by a second carrier, the vesicle-associated transporter (VAT), which can be inhibited by vesamicol. Peptides (P), adenosine triphosphate (ATP), and proteoglycan are also stored in the vesicle. Release of transmitter occurs when voltage-sensitive calcium channels in the terminal membrane are opened, allowing an influx of calcium. The resulting increase in intracellular calcium causes fusion of vesicles with the surface membrane and exocytotic expulsion of acetylcholine and cotransmitters into the junctional cleft (see text). This step can he blocked by botulinum toxin. Acetylcholine s action is terminated by metabolism by the enzyme acetylcholinesterase. Receptors on the presynaptic nerve ending modulate transmitter release. SNAPs, synaptosome-associated proteins VAMPs, vesicle-associated membrane proteins.

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. 

Q4 Cholinergic nerves are mainly affected. There is reduction in the enzyme choline acetyltransferase and a deficit in acetylcholine. 

Biochemical measurement of distinct levels of acetylcholine (McIntosh, 1941 Kasa et al., 1982) and its biosynthetic enzyme, choline acetyltransferase (ChAT) in cerebellar tissue (Kasa and Silver, 1969 Salvaterra and Foders, 1979 Hayashi, 1987 and others) indicated the presence of a cholinergic innervation in the cerebellum. ChAT activity varies among different lobules with the highest levels in the nodulus and ventral uvula. Following deafferentation of the cerebellar cortex, ChAT activity is considerably de-... 

Acetylcholine is synthesized from choline and acetyl coenzyme A through the action of the enzyme choline acetyltransferase and becomes packaged into membrane-bound vesicles. After the arrival of a nerve signal at the termination of an axon, the vesicles fuse with the cell membrane, causing the release of acetylcholine into the synaptic cleft. For the nerve signal to continue, acetylcholine must diffuse to another nearby neuron or muscle cell, where it will bind and activate a receptor protein. 

The enzyme choline acetyltransferase (EC 2.3.1.6) is the key enzyme in the synthesis of acetylcholine, whereas AChE is essential for the inactivation and regulation of acetylcholine at localized sites of neurotransmission. The mechanism of action of AChE involves an initial reaction where acetylcholine forms a complex with the enzyme, leading to acetylation and the release of choline. The reaction is reversible with the regeneration of de-acetylated enzyme. 

The synthesis of acetylcholine from acetyl CoA and choline is catalyzed by the enzyme choline acetyltransferase (ChAT) (Fig. 48.9). This synthetic step occurs in the presynaptic terminal. The compound is stored in vesicles and later released through calcium-mediated exocytosis. Choline is taken up by the presynaptic terminal from the blood via a low-affinity transport system (high and from the synaptic cleft via a high-affmity transport mechanism (low K. It is also derived from the hydrolysis of phosphatidylcholine (and possibly sphingomyelin) in membrane lipids. Thus, membrane lipids may form a storage site for choline, and their hydrolysis, with the subsequent release of choline, is highly regulated. 

Figure 2.4B Synthesis, release and degradation of acetylcholine. 1). The enzyme choline acetyltransferase catalyzes the acetylation of choline by acetyl CoA to form acetylcholine.

Not fully understood, but it has been shown that quinidine can inhibit the enzyme (choline acetyltransferase), which is concerned with the synthesis of acetylcholine at nerve endings. Neuromuscular transmission would be expected to be reduced if the synthesis of acetylcholine is reduced. Quinidine also inhibits the activity of plasma cholinesterase, which is concerned with the metabolism of suxamethonium. ... 

Acetylcholine (Sec. 11.11) is synthesized in the body s neurons. The enzyme choline acetyltransferase catalyzes its synthesis from acetyl-CoA (see A Word About... Thioesters, Nature s Acyl-Activating Groups on page 312) and choline. Write an equation for the reaction, using the formula CH3C—S—CoA for acetyl-CoA. 

Biosynthesis of ACh involves a reversible reaction in which an acetyl group is transferred from acetyl coenzyme A to choline by the enzyme choline acetyltransferase. The rate-limiting step in ACh s)mthesis is the availability of choline, which is transported into neuronal terminals from the extracellular space by sodium-dependent, high-affinity uptake systems. ACh s)mthesized in the cytosol is stored in vesicles via the action of the vesicular ACh transporter. In response to an action potential, vesicular ACh is released by exocytosis from cholinergic nerve terminals, where it can interact with two major types of receptors muscarinic... 

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