[Pharmacologic properties of partially purified glutamic acid decarboxylase (L-glutamate-1-carboxylyase, E.C. 4.1.1.15) from calf cerebral cortex].
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AIMS: Though glutamic acid is well known as a working excitatory in the CNS, its impact on the modulation of alcohol withdrawal symptoms and withdrawal fits are not yet clear. The study has been undertaken to examine the levels of glutamic acid in chronic alcohol-dependent patients at different stages of alcohol withdrawal and weaning and to examine any existence of any differences according to Cloninger's and Lesch's typologies. PATIENTS AND METHODS: One hundred and fifty-nine alcohol-dependent patients were assessed according to Cloninger's and Lesch's typologies and related to abstinence duration, age, and gender. Blood samples were taken for mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT) and glutamic acid, in order to find primarily any differences in glutamic acid according to the typologies, age, abstinence duration, and liver damage. RESULTS: There was no significant association between Cloninger's and Lesch's typologies. Cloninger's types 1 and 2 had an equal distribution of GGT and duration of abstinence, while Lesch's type I had more patients with high GGT, and more patients who were sober for a maximum of 2 days. Unlike in Lesch's types, glutamic acid levels did not differ according to Cloninger's types, as significantly higher glutamic acid values were found in Lesch's types I and IV. Glutamic acid values did not differ significantly in different age groups. CONCLUSIONS: Our study findings of varying glutamic acid levels seen in Lesch's typology, higher in types I and IV than in types II and III, are of significant clinical value and can be interpreted differently, as in type I high levels of glutamic acid is seen as a kindling phenomenon, while in type IV elevated levels might be related to either compulsivity of frequent repetition of drinking or withdrawal.
Glutamic acid metabolism in 24-hour starved 20-day pregnant and control non-pregnant rats, following intravenously administered [14C]-glutamic acid has been studied. The utilization of glutamate as a gluconeogenic precursor is not increased in late pregnancy under 24-hour starvation and it is regulated by the lower blood substrate availability. In addition, the steady state levels of glutamate, glutamine, aspartate, protein and glucose in blood, liver and skeletal muscle, together with tissue glycogen and lipids and metabolite composition pools, are given for both non-pregnant and pregnant rats.
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Adult rat hepatocytes in primary culture responded to epidermal growth factor (EGF) by increased DNA synthesis. When hepatocytes were cultured in Leibovitz L-15 medium, their response to EGF was low compared with that in Williams' medium E or Koga's medium L. Furthermore, female rat hepatocytes showed almost no response to the mitogenic action of EGF compared with male rat hepatocytes in L-15 medium. Addition of glutamic acid (1-20 mM) to EGF-containing L-15 medium not only enhanced DNA synthesis > tenfold in both male and female hepatocytes, but eliminated the sex differences in DNA synthesis. Aspartic acid, glutamine, or ornithine at 20 mM did not replace the glutamic acid effect on DNA synthesis. Proline also enhanced EGF-induced DNA synthesis, although it was less effective than glutamic acid. Therefore, this effect may be specific to a high concentration of glutamic acid. Glutamic acid by itself did not stimulate DNA synthesis at any concentrations tested. In the presence of glutamic acid, EGF showed a dose-dependent (0.5-20 ng/ml) stimulation of DNA synthesis with a maximal effect at 10 ng/ml. Almost the same effect was obtained with transforming growth factor alpha (0.5-20 ng/ml). Glutamic acid also induced an expansion of the mitogenic action of angiotensin II. Since glutamic acid did not affect [125I]EGF binding to hepatocytes or its processing, the effect may occur internal to the receptor. These results suggest that glutamic acid modulates the sensitivity of the hepatocyte response to mitogens.
The effects of different concentrations of L-ascorbic acid (Asc) on Na+-dependent binding of 3H-GABA and 3H-DL-glutamic acid to rat brain cortical synaptosomes were studied. Asc, at a concentration nearly equal to brain extracellular one (3 X 10(-4) M), had no effect on specific and nonspecific 5H-GABA binding. At higher concentrations (10(-3) M) Asc strongly inhibited, and at lower concentrations (10(-6) M) considerably stimulated 3H-GABA binding. At a concentration of 10(-5)-10(-3) M Asc tended to decrease 3H-DL-glutamic acid binding.
The effect of exogenous glutamic acid on nitrogenous and energetic metabolism of isolated perfused heart of the rat was studied under anoxia. Addition of 5 mM glutamic acid to the perfusate significantly increased the ATP level in anoxic heart. Perfusion of anoxic heart with 5 mM glutamic acid recovered the glutamate and aspartate tissue content and caused augmented production of alanine and succinate, while lactate formation did not change. In the presence of glutamic acid, the glutamine and asparagine contents in the heart-perfusate system markedly increased; however, the ammonia content did not reduce significantly. The effect on glutamic acid was reproduced by its transamination products, 5 mM aspartic and 5 mM alpha-ketoglutaric acids, and was totally eliminated by 2 mM aminooxyacetic acid, an inhibitor of transaminases. These data suggest that the glutamate-induced protective effect of ATP is probably related to the stimulation of substrate phosphorylation in mitochondria, resulting in succinate synthesis that is coupled with glutamate transamination.
L-Glutamic acid and kainic acid injected into the cisterna magna of dogs, produced a dose-dependent increase in blood pressure and a decrease in heart rate. In contrast, intravenous injection of both compounds was ineffective. The hypertension was probably due to an increase in sympathetic tone as guanethidine prevented the rise in blood pressure induced by central administration of L-glutamic acid and kainic acid. Kainic acid was 1 000 fold more potent than L-glutamic acid.
Glutamic acid content of semen was determined photometrically in over 400 semen specimens. Glutamatic acid content was found to increase proportionately to temperature in the first few hours post ejaculation. The glutamate estimation should therefore be performed on semen at 30 min. after ejaculation. The frequency distribution of glutamic acid concentration with 400 unselected specimens, 50 "normozoospermias" as well as 42 azoospermias is shown. The mean value of normozoospermias was 10.6 mg% (+/- 4.6 mg%) that of azoospermias 7.7 mg% (+/- 4.7 mg%). There was no correlation found between glutamic acid content and pH value. A correlation however, was demonstrated between glutamic acid and following: sperm count, citrate concentration, gamma-GT and carnitine. No correlation to fructose content was detectable. That suggests that glutamate gets to the ejaculate with the secretions from the prostate gland and epididymis whereas the seminal vesicles do not play a role in the level in the total semen.
Starting from glutamic acid, different types of surfactants have been synthesised by using original trimodular strategies. Monosubstituted zwitterionic amides of glutamic acid obtained with excellent yields show good surface activity. The grafting of a second hydrophobic side-chain leads to bicatenar cationic surfactants or to disubstituted nonionic cyclic compounds. In order to reduce the hydrophobic character of the bicatenar surfactants, a second synthetic method has been developed, allowing the introduction of a polar sugar group into these molecules. The surfactant properties of several of the products have been determined by physico-chemical methods such as surface tension measurements and compression isotherm studies by means of a Langmuir balance.
L-Glutamic acid uptake by bovine pulmonary arterial endothelial cells in culture increased linearly with time up to 30 min and did not show saturation with increased substrate concentration up to 6 X 10(-3) M. The uptake per cell decreased as cell density increased and was lowest when the cells became fully confluent. Most of the uptake was sodium dependent, although the relative contribution of sodium-independent uptake increased with an increase in cell density. Cysteic and aspartic acid strongly inhibited L-glutamic acid uptake, but at higher cell densities this effect was less pronounced than at low densities. Other amino acids, including leucine, glutamine, and serine, exerted a modest inhibitory effect at both high and low cell densities. Thus pulmonary arterial endothelial cells contain similar membrane transport systems for L-glutamic acid as those previously described for fibroblasts, hepatocytes, and nerve cells. However, quantitative properties of the transport systems differ depending on the state of cellular density in monolayers.
Hb S Travis is a previously undescribed sickling hemoglobin with two amino acid substitutions in the beta chain: beta6 Glu leads to Val and beta142 Ala leads to Val. The beta6 Glu leads to Val mutation imparts to Hb S Travis the characteristic properties of sickling hemoglobin, namely its association with erythrocyte sickling, the insolubility of the hemoglobin in the reduced form, and a minimum gelling concentration value identical to Hb S. Unlike Hb S, Hb S Travis exhibits an increased oxygen affinity and a decreased affinity for 2,3-bisphosphoglycerate and inositol hexakisphosphate. In addition, the variant hemoglobin's tendency to autoxidize and its mechanical precipitability suggest that there are conformational differences between Hb S and Hb S Travis.
A significant increase in the plasma levels of glutamic acid and a significant decrease in aspartic acid and taurine in epileptic patients and their first degree relatives was reported more than a decade ago and an underlying genetic basis for these amino acid changes was suggested. The main objective of the present study was to determine the plasma levels of glutamic acid, aspartic acid and taurine in El mice which are an inbred epileptic mutant mouse strain. The results show a significant increase in plasma glutamic acid but no changes in aspartic acid or taurine in the epileptic mice as compared to controls. The data provide the first evidence of a significant increase in plasma glutamic acid in an animal model of hereditary epilepsy and substantiate the hypothesis that a genetic defect underlies the elevated plasma glutamic acid levels in association with epilepsy. The findings are also compatible with neurochemical and neurophysiological evidence implicating glutamic acid in the mechanism of seizures.
Kainic acid lesion of the 'centre médian'-parafascicular complex of the thalamus inducing a degeneration of the thalamostriatal neurons was followed by a decrease in choline acetyltransferase (ChAT) in the rostral part of the striatum in the rat. This decrease in ChAT was concomitant with an increase in glutamate decarboxylase, high-affinity glutamate uptake and apparent dopamine turnover. These results suggest that the thalamostriatal partly cholinergic input exerts a powerful control over GABAergic, glutamatergic and dopaminergic neurons in the basal ganglia.