Dopa decarboxylase and

Baylin, S. B., Abeloff, M. D., Goodwin, G., Carney, D. M and Gazdar, A. F. (1980). Activities of L-dopa decarboxylase and diamine oxidase (histaminase) in human lung cancers and decarboxylase as a marker for small (oat) cell cancer in cell culture. Cancer Res. 40 1990-1994. 

Another example is to be found in the drug therapy of Parkinson s disease. The use of L-dopa (levodopa) as a prodrug for dopamine has already been described. However, to be effective, large doses of L-dopa (3-8 g per day) are required, and over a period of time these dose levels lead to side-effects such as nausea and vomiting. L-Dopa is susceptible to the enzyme dopa decarboxylase and as a result, much of the L-dopa administered is decarboxylated to L-dopamine before it reaches the central nervous system (Fig. 8.21). 

The catecholamines are biosynthesized from the amino acid L-tyrosine as outhned in Figure 7.1. The known biochemical events leading to catecholamine metabolism and urinary excretion are also summarized in Figure 7.1. There is evidence that functioning pheochromocytomas have the various enzymes necessary for the conversion of tyrosine to catecholamines, and the level of activity of some of these enzymes (tyrosine hydroxylase, Dopa decarboxylase and dopamine p-hydroxylase) is higher than in normal adrenal tissue." ... 

Levodopa is used to treat Parkinson s disease. Explain why it is used together with drugs that inhibit dopa decarboxylase and COMT. 

The results show that if the extract contained two individual enzymes, DOPA decarboxylase and 5-HTP decarboxylase, then not only must DOPA have the same affinity for each enzyme, but 5-HTP must also have the same affinity for each enzyme. Alternatively the extract could contain only one decarboxylase capable of decarboxylating both DOPA and 5-HTP. As the second alternative is the more probable one, these results provide strong, though by themselves not conclusive, evidence that in the rabbit kidney extract one enzyme is responsible for the decarboxylation of both substrates. 

That not only DOPA decarboxylase and 5-HTP decarboxylase, but also the histidine decarboxylase (having its optimum activity in the range pH... 

In rats treated with the liver carcinogen diethylnitrosamine (DENA), the mean activities of histidine decarboxylase (measured at pH 8 0), DOPA decarboxylase and 5-HTP decarboxylase in the liver were significantly lower than the corresponding mean values in the livers of control rats. In both the control and DENA-treated series, however, a positive correlation was found between the activities of these three enzymes . When rats were maintained on a tryptophan-deficient diet, it was found that the mean activities of histidine decarboxylase (pH 8-0), DOPA decarboxylase and 5-HTP decarboxylase in the livers of the tryptophan-deficient animals were significantly... 

The other physiologically important monoamine is 5-hydroxytryptamine (serotonin or 5-HT). It is formed from tryptophan via 5-hydroxytryptophan (5-HTP) Figure 5.2). The nature and properties of tryptophan-5-hydroxy-lase is still obscure, though the hydroxylation of tryptophan in vivo has been demonstrated. There is no clear evidence that this conversion occurs in brain tissue. The decarboxylation of 5-HTP, however, takes place in brain and the decarboxylating enzyme is found in all cerebral areas which contain 5-hydroxytryptamine. 5-HTP decarboxylase is closely related to, if not identical with, DOPA decarboxylase - and agents which inhibit dopan ine formation similarly inhibit the production of 5-hydroxytryptamine. There... 

Identify the compounds that inhibit dopa decarboxylase and catechol-O-methyltransferase and describe their use in parkinsonism. 

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... 

Caffeic acid is an inhibitor of the enzymes DOPA-decarboxylase and 5-lipoxygenase. It is an analgesic and anti-inflammatory, and promotes intestinal motility (Adzet and Camarasa 1988). It is of widespread occurrence and is found in green and roasted coffee beans. 

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. 

Interference with transmitter synthesis, e.g. inhibition of enzymes such as tyrosine hydroxylase, dopa decarboxylase, and dopamine 8-oxidase. 

IX. 4 -0-Methylation of 3-hydroxy-V-methylcoclaurine The several upstream biosynthetic genes in these steps, tyrosine/DOPA decarboxylase and tyrosine aminotransferase, have been isolated and characterized [13, 14]. 

That the synthesis of epinephrine may involve the decarboxylation to DOPA amine prior to introduction of the hydroxyl group is suggested by the following investigators. Vinet " claimed that the adrenal medulla is capable of converting DOPA amine to epinephrine in vitro. Schapira " reported that the adrenal medulla did not contain DOPA decarboxylase and that epinephrine inhibited the decarboxylation of DOPA. This assumes that DOPA is converted to DOPA amine in some other part of the body and finally transferred to epinephrine in the adrenal medulla. 

Dihydroxyphenylserine is decarboxylated very poorly if at all by kidney preparations. Positive results were obtained only upon incubation with large amounts of kidney extract for periods of up to 5 hours. Under such conditions the formation of arterenol can be demonstrated. On the other hand a rate of decarboxylation of 3,4-dihydroxyphenylserine comparable to that of DOPA has been reported by Sourkes et with beef adrenal homogenates. Thus, it may be concluded that an unsubstituted amino group is necessary for action by DOPA decarboxylase and that the presence of a hydroxy group on the /3-carbon atom reduces the rate of decarboxylation considerably, but not absolutely, by kidney and adrenal medulla. 

That not only DOPA decarboxylase and 5-HTP decarboxylase, but also the histidine decarboxylase (having its optimum activity in the range pH 8-0-9 5) are the same enzyme is also suggested by inhibition studies, a-Methyl-DOPA, for example, is a potent inhibitor of all three enzymes other pc-methylamino-acids behave similarly . 

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