Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.1.22 (cystathionine beta-synthase)
 965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A clinically benign form of persistent hypermethioninaemia with probable dominant inheritance was demonstrated in three generations of one family. Plasma methionine concentrations were between 87 and 475 mumol/L (normal mean 26 mumol/L; range 10-40 mumol/L); urinary methionine and homocystine concentrations were normal. Plasma homocystine, cystathionine, cystine and tyrosine were virtually normal. The concentrations in serum and urine of metabolites formed by the methionine transamination pathway were normal or moderately elevated. Methionine loading of two affected family members revealed a diminished ability to catabolize methionine, but the activities of methionine adenosyltransferase and cystathionine beta-synthase were not decreased in fibroblasts from four affected family members. Fibroblast methylenetetrahydrofolate reductase activity and its inhibition by S-adenosylmethionine were also normal, indicating normal regulation of N5-methyltetrahydrofolate-dependent homocysteine remethylation. Serum folate concentrations were not increased. The findings in this family differ from those previously described for known defects of methionine degradation. Since the hepatic and fibroblast isoenzymes of methionine adenosyltransferase differ in their genetic control, this family's biochemical findings appear consistent with a mutation in the structural gene for the hepatic methionine adenosyltransferase isoenzyme.
 ...
PMID:Persistent hypermethioninaemia with dominant inheritance. 152 87

The experiments described here were set up (a) to investigate the effect of age and (b) to investigate the effect of giving five diets which varied in methionine and choline or betaine contents on some of the enzymes that metabolize these nutrients in chick liver. Growth and carcass composition of the chicks fed on the different diets were also examined. There was no obvious relationship between age and enzyme activity in young chicks. Only a diet low in methionine (but not one low in choline) showed a significant decrease in growth and a change in carcass composition. The effects of diet on enzyme activity were complex. Choline oxidase (EC 1.1.3.17) activity was affected by the level of choline in the diet, being high when choline was present at high levels, especially when methionine was limiting. 5-Methyltetrahydrofolate homocysteine methyltransferase (EC 2.1.1.3) had a high activity in the livers of chicks fed on a conventional diet compared with those given semi-purified diets. Other enzymes showed minor changes in response to the diet. The diet low in methionine showed a lower activity of cystathionine beta-synthase (EC 4.2.1.22) and slightly higher activities of methionine adenosyltransferase (EC 2.5.1.6) and betaine-homocysteine methyltransferase (EC 2.1.1.5; compared with other diets), suggesting that this diet encouraged re-methylation of homocysteine at the expense of trans-sulphuration to cystathionine. The findings obtained in these studies form a useful basis for further investigation of the metabolic interrelationships between methionine and related nutrients.
 ...
PMID:Changes in body-weight, composition and hepatic enzyme activities in response to dietary methionine, betaine and choline levels in growing chicks. 169 35

Addition of serum, obtained from patients suffering from an acute psychosis characterized by dysperceptions, to the culture media of fibroblasts altered the amino acid metabolism in these cells. After subculturing of fibroblasts in the presence of serum obtained from these patients, the concentrations of both serine and methionine were decreased in the medium as well as in the fibroblasts. Moreover, the concentration of taurine in the fibroblasts was increased. The specific activities of serine hydroxymethyltransferase and cystathionine beta-synthase were also measured in the fibroblasts. It was found that both enzyme activities were significantly higher after subculturing with patients' serum as compared with serum obtained from healthy controls. It is concluded that a factor, present in the serum of these acute psychotic patients, is responsible for the observed changes in serine, taurine, and methionine concentrations in the fibroblasts as well as for the increased enzyme activities mentioned.
 ...
PMID:Changes in serine metabolism by a serum factor present in a group of episodic psychotic patients. 175 1

Regulation of the two enzymes in reverse trans-sulfuration was investigated in Saccharomyces cerevisiae. In wild-type strains, cystathionine gamma-lyase, but not cystathionine beta-synthase, was depressed nearly 15-fold if cells were starved for both inorganic and organic sulfur compounds. In a met17 strain which is defective of O-acetylserine and O-acetylhomoserine sulfhydrylase, the same enzyme was derepressed if organic sulfur compounds were limited; the repressive effect was in the order of glutathione greater than methionine greater than cysteine. The repressive effect of methionine was not observed, however, in a cys2 cys4 strain which is deficient of serine O-acetyltransferase and cystathionine beta-synthase, indicating that methionine itself is not the effector. The weak repressive effect of cysteine was attributed to inefficient uptake of this amino acid. Our observations indicate that cystathionine gamma-lyase is the target of regulation in reverse trans-sulfuration and that cysteine is very likely to be the effector of this regulation.
 ...
PMID:Regulation of cystathionine gamma-lyase in Saccharomyces cerevisiae. 178 5

We examined the change in glutathione metabolism in vitamin B-6-deficient rats. Vitamin B-6-deficient rats were fed a vitamin B-6-deficient diet containing 0.56% methionine and 0.075% cystine for 8 wk. Controls were fed an identical diet supplemented with 10 mg pyridoxine hydrochloride/kg diet. Glutathione concentrations in each organ examined were similar in control and vitamin B-6-deficient rats, and the values were comparably lower after intraperitoneal injection of diethylmaleate. However, buthionine sulfoximine caused a significantly greater decrease in glutathione levels in the liver and lungs of vitamin B-6-deficient rats relative to controls. Glutathione peroxidase activity in the liver of vitamin B-6-deficient rats was higher than in control animals; however, glutathione transferase activity in tissues other than liver of vitamin B-6-deficient rats was higher than in the controls. The activities of gamma-glutamyl-transferase in the liver and spleen of vitamin B-6-deficient rats were significantly lower than control values. The holoenzyme activities of cystathionine beta-synthase and cystathionine gamma-lyase in the liver of vitamin B-6-deficient rats were markedly reduced. These findings indicate that although the activities of enzymes that synthesize cysteine from methionine were decreased by vitamin B-6 deficiency, the level of synthesis and supply of cysteine in vitamin B-6-deficient rats were sufficient to maintain the same glutathione level as in controls, and that glutathione utilization in the liver was accelerated by vitamin B-6 deficiency.
 ...
PMID:Glutathione levels and related enzyme activities in vitamin B-6-deficient rats fed a high methionine and low cystine diet. 188 Jun 14

A yeast strain highly resistant to propargylglycine (an inhibitor of cystathionine gamma-lyase) was isolated from air. It was partially characterized, but it has not been identified with any known yeast species. Its sulphur amino acid metabolism differed from that of other fungi by the lack of the reverse transsulphuration pathway from methionine to cysteine, as no activity of cystathionine beta-synthase or cystathionine gamma-lyase was found. The functional lack of this pathway was confirmed by growth tests and by experiments with [35S]methionine. In contrast to Saccharomyces cerevisiae neither homocysteine synthase nor the sulphate assimilation pathway were repressible by methionine in the new strain; on the contrary, a regulatory effect of cysteine was observed.
 ...
PMID:A yeast with unusual sulphur amino acid metabolism. 207 24

To assess the extent to which low hepatic gamma-cystathionase levels affect methionine flux to cysteine in hepatocytes, the effect of inhibition of gamma-cystathionase activity with propargylglycine on the metabolism of L-[35S]methionine was determined in studies with freshly isolated rat hepatocytes. gamma-Cystathionase activity was inhibited 25%, 42%, 63% and 76% (maximal inhibition) by treatment with 2.5 mumol/L, 0.01 mmol/L, 0.02 mmol/L and 2 mmol/l propargylglycine, respectively. Inhibition of gamma-cystathionase activity with up to 0.02 mmol/L propargylglycine had no statistically significant effect on [35S]glutathione, [35S]sulfate or [35S]cysteine formation from [35S]methionine. However, treatment of cells with 2 mmol/L propargylglycine markedly inhibited the metabolism of [35S]methionine to [35S]glutathione by 93%, to [35S]sulfate by 88% and to [35S]cysteine by 89%; [35S]cystathionine accumulation in these incubation systems was 60 times control. Hepatic gamma-cystathionase activity in premature infants has been reported to be about 23% of mature levels (Zlotkin and Anderson, 1982; Pediatr. Res. 16: 65-68); this level of gamma-cystathionase activity may limit cysteine synthesis by the methionine transsulfuration pathway. No evidence for cysteine synthesis from serine and sulfide, which can be catalyzed by cystathionine beta-synthase, or for methionine metabolism by an S-adenosylmethionine-independent pathway was obtained.
 ...
PMID:Role of the transsulfuration pathway and of gamma-cystathionase activity in the formation of cysteine and sulfate from methionine in rat hepatocytes. 211 6

Severe homocysteinemia due to genetic defects either of pyridoxal 5-phosphate (PLP)-dependent cystathionine beta-synthase (CBS) or of enzymes in vitamin B12 and folate metabolism is associated with very early-onset vascular disease. Therefore, we studied homocysteine metabolism in 72 patients presenting before the age of 55 years with occlusive arterial disease of cerebral, carotid, or aorto-iliac vessels. Twenty patients (28%) had basal homocysteinemia; and 26 patients (36%) had abnormal increases of plasma homocysteine after peroral methionine loading, which exceeded the highest value for 46 comparable controls and was within the range for 20 obligate heterozygotes for homocystinuria due to CBS deficiency. Basal plasma homocysteine content was strongly and negatively correlated to vitamin B12 and folate concentrations. Plasma PLP was depressed in most patients but there was no correlation between PLP and homocysteine values. In 20 patients, treatment with pyridoxine hydrochloride (240 mg/day) and folic acid (10 mg/day) reduced fasting homocysteine after 4 weeks by a mean of 53%, and methionine response by a mean of 39%. These data show that a substantial proportion of patients with early-onset vascular disease have impaired homocysteine metabolism, which may contribute to vascular disease, and that the impaired metabolism can be improved easily and without side effects.
 ...
PMID:Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease. Effects of pyridoxine and folic acid treatment. 240 53

Cystathionine beta-synthase deficiency results in severe homocysteinaemia, precocious arteriosclerosis and frequent thromboembolism. In addition, antithrombin III activity and factor VII are low. Arteriosclerosis seems to be increased in heterozygotes as well (cystathionine beta-synthase gene dosage 50%) but rare in Down syndrome (cystathionine beta-synthase gene dosage 150%). In the present study total plasma homocysteine was high in three homozygotes, slightly increased in 20 obligate heterozygotes but not reduced in nine subjects with Down syndrome when compared to controls. After methionine loading, increases of homocysteine were pathologically high in 14 of 20 heterozygotes but was not, as expected, low in subjects with Down syndrome. Antithrombin III activity and factor VII antigen tended to be low in homozygotes but were normal in heterozygotes. In Down syndrome antithrombin III activity was reduced and factor VII antigen normal. There were no correlations between levels of homocysteine, antithrombin III activity and factor VII antigen. Thus, subjects with Down syndrome seem not to exhibit the expected gene dosage effect on homocysteine metabolism which could explain their reduced proneness to develop arteriosclerosis, nor do antithrombin III activity or factor VII antigen seem to be related to homocysteine metabolism.
 ...
PMID:Homocysteine, factor VII and antithrombin III in subjects with different gene dosage for cystathionine beta-synthase. 253 42

Thrombogenesis and accelerated atherogenesis occur in the homocystinurias, both those due to recessively inherited cystathionine beta-synthase deficiency and to disorders of remethylation of homocysteine to methionine. The evidence strongly implicates high levels of plasma homocysteine as the mediator. Homocysteine damages cultured human venous and arterial endothelial cells and enhances detachment from their substrate, changes not found with comparable concentrations of other amino acids tested. Homocysteine is oxidized in vitro to homocystine in an oxygen-dependent reaction producing hydrogen peroxide. Since the effects of homocysteine in cell cultures can be prevented by catalase, hydrogen-peroxide-induced injury may be the mechanism responsible. Five different laboratories have documented an association between mild homocysteinaemia and premature vascular disease. The majority of affected patients are heterozygotes for cystathionine beta-synthase deficiency whose endothelial cells may have an enhanced susceptibility to injury by homocysteine. Mild homocysteinaemia also occurs in chronic renal failure in which vascular disease is prominent. Mechanisms linking mild homocysteinaemia and possible vascular effects are not yet understood, but could involve prostaglandins and oxidized low-density lipoprotein, and possibly also free radicals.
 ...
PMID:Mechanisms of thrombogenesis and accelerated atherogenesis in homocysteinaemia. 268 Aug 9


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>