Acetylation, choline

The synthesis reaction is a single step catalyzed by the enzyme choline acetyl transferase (ChAT) ... 

The processes involved in neurochemical transmission in a cholinergic neuron are shown in Figure 9.2. The initial substrates for the synthesis of acetylcholine are glucose and choline. Glucose enters the neuron by means of facilitated transport. There is some disagreement as to whether choline enters cells by active or facilitated transport. Pyruvate derived from glucose is transported into mitochondria and converted to acetylcoenzyme A (acetyl-CoA). The acetyl-CoA is transported back into the cytosol. With the aid of the enzyme choline acetyl-transferase, acetylcholine is synthesized from acetyl-CoA and choline. The acetylcholine is then transported into and stored within the storage vesicles by as yet unknown mechanisms. 

C) Inhibition of synthesis of acetylcholine by inhibiting choline acetyl transferase... 

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). 

By and large the drug treatments for AD merely attempt to diminish the impact of the psychiatric symptoms. Major and minor tranquilizers and antidepressants, which we will be discussing shortly, can help in the management of AD victims in the early stages of the condition. Attempts have been made to treat apparent decreases in the amount of acetylcholine in the hippocampal area of the brain. This is due to lower choline acetyl transferase activity. Acetylcholinesterase... 

Patients with ALS/PDC also show a moderate loss of choline acetyl transferase activity in the midfrontal and inferior parietal cortex and a severe loss in the superior temporal cortex (Masliah et al., 2001). This deficit is similar to that seen in Alzheimer disease and less severe than in Lewy body disease. Thus, cholinergic deficits in the neocortex may contribute to some of the cognitive alterations in ALS/PDC. 

Hebb, C., Morris, D. and Smith, M.W. (1969). Choline acetyl transferase activity in the brain of goldfish acclimated to different temperatures. Comparative Biochemistry and Physiology 28,29-36. 

Acetylcholine is a major neurotransmitter in the neostriatum. Within the neostriatum, both the content of acetylcholine and the specific activity of choline acetyl transferase,... 

Cervini, R., Houbou, L., Pradat, P.F., Bejanin, S., Mallet, J., Berrard, S. (1995). Specific vesicular acetylcholine transporter promoters he within the first intron of the rat choline acetyl-transferase gene. J. Biol. Chem. 270 24654—7. 

ACh is found to be stored within the terminals of motor neurons. Detailed analysis has demonshated that ACh is stored within small packages called synaptic vesicles that are concenhated around active zones on the presynaptic membrane. These active zones have been identified as specialized sites for neurohansmitter containing vesicle release. The enzyme for synthesizing ACh from choline and acetyl-Co A, choline acetyl transferase, is also found within the presynaptic terminal. Choline acetyl transferase is found in the cytoplasm. When ACh is synthesized it is pumped into synaptic vesicles by means of a specific carrier molecule located in the vesicle membrane. Once released, ACh subsequently diffuses across the synapse and activates nicotinic ACh receptors localized on the plasma membrane of the postsynapdc muscle cell producing depolarization of the muscle (see below). 

Choline is a cholinergic agonist, choline acetyl-transferase substrate therefore, it exerts toxicity by... 

Hagg, T., Fass, H. B., Vahlsing, H. L., Manthorpe, M., Conner, J. M., and Varon, S., Nerve growth factor (NGF) reverses axotomy-induced decreases in choline acetyl-transferase, NGF receptor and size of medial septum cholinergic neurons, Brain Res., 505,29, 1989. 

Acetylcholine (ACh) Choline Acetyl Co-A CAT Enzymatic (AChE) Chohne recycled... 

Hayashi M (1987) Ontogeny of glutamic acid decarboxylase, tyrosine hydroxylase, choline acetyl transferase, somatostatin and substance P in monkey cerebellum. Dev. Brain Res., 32, 181-186. 

Kan KKS, Chao LP, Eng LF (1978) Immunohistochemical localization of choline acetyl-transferase in rabbit spinal cord and cerebellum. Brain Res., 146, 221-229. 

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