Glutamic acid, brain decarboxylase inhibition

SNA does not affect the concentrations of histamine and glutamic add, but It decreases the activity of glutamic acid decarboxylase and reduces the concentrations of gamma-aminobutyric acid (GABA) In rat brain. 5 GABA release Is Inhibited by acute administration, but not by chronic treatment. 5 SNA Increases serum creatinine phosphoklnase content In stressed rats. Recently, SNA was found to decrease methionine-enkephalin content In the medulla oblongata and mldbraln In the mouse, whereas other areas remained unaffected.48... 

Ribak CE, Vaughn JE, Saito K (1978) Immunocytochemical localization of glutamic acid decarboxylase in neuronal somata following colchicine inhibition of axonal transport. Brain Res., 140, 315-322. 

Cysteine was also an elTective inactivator in vitro] the closely related compound penicillamine (/3,j8-dimethylcysteine) is slightly more reactive - . Penicillamine inhibits the transaminases of rat liver and the glutamic acid decarboxylase of mouse brain . The formation of thiazolidine derivatives by reaction of cysteine or penicillamine with pyridoxal phosphate proceeds... 

A. Acute overdose. Isoniazid produces acute toxic effects by reducing brain pyridoxal 5-phosphate, which is the active form of vitamin Bg and an essential cofactor for the enzyme glutamic acid decarboxylase. This results in lower CNS levels of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, which leads to uninhibited electrical activity manifested as seizures. INH may also Inhibit the hepatic conversion of lactate to pyruvate, exacerbating the lactic acidosis from seizures. 

Phenylpyruvic and phenyllactic acids inhibit glutamic acid decarboxylase in vitro. If the inhibition exists also in vivo, no y-isobutyric acid is produced. This compound seems to play an important role in the brain-blood barrier regulation. 

In the case of hyperphenylalaninaemia, which occurs ia phenylketonuria because of a congenital absence of phenylalanine hydroxylase, the observed phenylalanine inhibition of proteia synthesis may result from competition between T.-phenylalanine and L-methionine for methionyl-/RNA. Patients sufferiag from maple symp urine disease, an inborn lack of branched chain oxo acid decarboxylase, are mentally retarded unless the condition is treated early enough. It is possible that the high level of branched-chain amino acids inhibits uptake of L-tryptophan and L-tyrosiae iato the brain. Brain iajury of mice within ten days after thek bkth was reported as a result of hypodermic kijections of monosodium glutamate (MSG) (0.5—4 g/kg). However, the FDA concluded that MSG is a safe kigredient, because mice are bom with underdeveloped brains regardless of MSG kijections (106). 

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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