Decarboxylase, DOPA glutamic

Phenyllactic and phenylpyruvic acids have an inhibitory effect on dopa decarboxylase and glutamic decarboxylase activity, but phenylalanine does not. Phenyl-acetic acid in equimolar concentrations had only half the inhibitory power of the two other metabolites. These findings might explain why low-phenylalanine diets restore pigmentation to normal in phenylke-tonuric individuals. 

Cenci, M. A., Lee, C. S. and Bjorklund, A. (1998). L-DOPA-induced dyskinesia in the rat is associated with striatal overexpression of prodynorphin-and glutamic acid decarboxylase mRNA. Eur. J. Neurosci. 10(8), 2694-2706. 

Steps in the formation of classical neurotransmitters. AADC, amino acid decarboxylase AChE, acetylcholinesterase CAT, choline acetyltransferase COMT, catechol-O-methyltransfeiase DBH, dopamine P-hydroxylase DA, dopamine DOPA, dibydroxyphenylalanine GABA-T, GABA transaminase GAD, glutamic acid decarboxylase HD, histidine decarboxylase 5-HTP, 5-hydroxytrytophan MAO, monoamine oxidase PNMT, phenylethanolamine N-methyltransferase TH, tyrosine hydroxylase TPH, tryptophan hydroxylase. 

Specific decarboxylases are known for a majority of the amino acids, and several are prime targets for inactivation by virtue of their substantial medicinal importance. These include aromatic-amino-acid decarboxylase, which is responsible for the production of dopamine (DOPA) orithine decarboxylase, which supplies the p amine putrescine and glutamate decarboxylase, which converts glutamate to the inhibitory neurotransmitter y-aminobutyric acid (GABA). The accepted mechanism of these enzymes involves decarboxylation of the amino acid to yield a resonance-stabilized carbanion at the a-carbon of the substrate. The intermediate is then protonated with retention of configuration to yield product (Walsh, 1979, p. 800). 

Acetylcholine is formed from choline (which is also an important constituent of phospholipids) and acetyl CoA under the catalytic influence of choline acetyl-ase. It is hydrolised by acetylcholinesterase or choline esterase. Two important steps in the formation of noradrenaline from tyr dopa decarboxylase and dopamine hydroxylase. Adrenaline is formed from noradrenaline by phenyl ethanolamine A -methyltransferase. Both noradrenaline and adrenaline are metabolised by catechol 0-methyl transferase or monoamine oxidase. Some later steps in their metabolism involve aldehyde dehydrogenase and alcohol dehydrogenase (aldehyde reductase), After hydroxylation to its 5-hydroxy derivative, tryptophan is converted by 5-hydroxytryptophan decarboxylase to 5-hydroxytryptamine (serotonin). The major routes of serotonin metabolism involve either monoamine oxidase or hydroxyindole 0-methyltransferase. Histamine is synthesised from histidine by histidine decarboxylase, and is metabolised by either diamine oxidase or histamine Af-methyltransferase. Gamma aminobutyric acid is formed by glutamate decarboxylase and metabolised by... 

Amino acid decarboxylases shown to require pyridoxal phosphate are the following (1) tyrosine, (2) arginine, (3) lysine, (4) ornithine, (5) glutamic acid and (6) dopa (3,4-dihydroxyphenylalanine). 

The problem of pathogenesis has received more attention in the case of phenylketonuria than in most other inborn errors of metabolism. As soon as the intoxication theory was put forward, and supporting evidence in the results of dietary treatment accumulated, the search began. Early hypotheses incriminated one or other of the abnormal metabolites of phenylalanine, e.g. phenylacetic acid [63], known to affect the C.N.S., o-tyramine [64] (which probably does not occur). Several of these metabolites can inhibit such enzymes as DOPA-decarboxylase, tryptophan hydroxylase and glutamic decarboxylase of brain [65]. In fact, the concentrations of serotonin, noradrenaline and adrenaline in the blood are low in phenylketonuria [65, 66] and some theories of pathogenesis have considered that lack of these and other neurotransmitter substances at the synapses, caused by inhibition of the relevant enzyme, was the cause of the neurological disease. This was difficult to combine with the demonstrable deficiencies in... 

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