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

Homocysteine desulphurase (EC 4.4.1.2) and serine sulphydrase (EC 4.2.1.22) activities in various lines of Trichomonas vaginalis, both metronidazole resistant and sensitive, and other trichomonad species were assessed. T. vaginalis contained the highest homocysteine desulphurase and serine sulphydrase activities of all the species. Although the levels of the enzyme activity in T. vaginalis isolates differed, no correlation between the activities and sensitivity to metronidazole was apparent. T. vaginalis homocysteine desulphurase catalysed both the hydrolysis of homocysteine to hydrogen sulphide, ammonia, and 2-oxoacid, and an exchange reaction between homocysteine and 2-mercaptoethanol. Homocysteine desulphurase was detected as a single enzyme band on isoelectric focusing, whereas several isoenzymes of serine sulphydrase were found. There were large differences in serine sulphydrase isoenzyme patterns between T. vaginalis lines and between species. Several isoenzymes were amplified in cells grown with 10(-5) M DL-propargylglycine for 24 hr. T. vaginalis homocysteine desulphurase and serine sulphydrase activities were inhibited by bithionol, hexachlorophene, and dichlorophene. These compounds also inhibited growth in vitro of T. vaginalis at concentrations similar to those that inhibited the enzymes.
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PMID:Trichomonas species: homocysteine desulphurase and serine sulphydrase activities. 349 28

The activities of choline oxidase and betaine-homocysteine methyltransferase increased markedly in pre-ruminant lamb liver after birth and subsequently decreased when the lambs reached the ruminant state, while the developmental changes in hepatic 5-methyl-H4folate-homocysteine methyltransferase were negatively correlated with those of betaine-homocysteine methyltransferase. Hepatic phospholipid methyltransferase was elevated almost four-fold by the 10th postnatal day, but declined thereafter. Hepatic glycine methyltransferase in one-day-old lambs increased 55-fold, compared with that of fetuses, and thereafter decreased dramatically with age. Guanidoacetate methyltransferase, glycine methyltransferase and betaine-homocysteine methyltransferase in sheep pancreas increased markedly with age and were many times higher than the hepatic enzymes in adult sheep. Choline oxidase, betaine-homocysteine methyltransferase, cystathionine beta-synthase and glycine methyltransferase in adult sheep liver were much lower than those in rat. These results illustrate the conservative features of methyl group metabolism in postruminant sheep.
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PMID:Developmental changes in the activities of enzymes related to methyl group metabolism in sheep tissues. 351 Aug 9

Homocystinuria commonly affects the central nervous system (CNS), primarily as mental retardation, seizures, and stroke. Case reports have long suggested a predisposition to schizophrenia, but no careful study of predisposition to psychiatric illness has been performed. Accordingly, we evaluated 63 persons with homocystinuria due to cystathionine beta-synthase deficiency for psychiatric disturbance, intelligence, evidence of other CNS problems, and responsiveness to vitamin B6. The overall rate of clinically significant psychiatric disorders was 51%, predominated by four diagnostic categories: episodic depression (10%), chronic disorders of behavior (17%), chronic obsessive-compulsive disorder (5%), and personality disorders (19%). The average IQ was 80 +/- 27 (1 SD); and an IQ of less than or equal to 79 was two-thirds more common among vitamin B6-nonresponsive patients compared to vitamin B6-responsive patients. Aggressive behavior and other disorders of conduct were particularly common among patients with mental retardation and among vitamin B6-nonresponsive patients.
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PMID:Psychiatric manifestations of homocystinuria due to cystathionine beta-synthase deficiency: prevalence, natural history, and relationship to neurologic impairment and vitamin B6-responsiveness. 359 41

The alleviation mechanism of methionine toxicity by dietary glycine was investigated in weanling rats fed a high-methionine diet. When rats were fed a 10% casein diet containing 2% methionine, the activities of methionine adenosyltransferase, cystathionine beta-synthase, and cystathionine gamma-lyase, which participate in the methionine metabolism in the transsulfuration pathway, were significantly enhanced. But the addition of 2% glycine to the high methionine diet did not cause further increase in these enzyme activities; the activities of methionine adenosyltransferase and cystathionine beta-synthase were rather decreased while cystathionine gamma-lyase activity was not altered. Methionine transaminase activity was essentially insensitive to the dietary addition of methionine and glycine. In rats fed a high methionine diet, the hepatic methionine level was significantly increased with a concomitant decrease in the levels of glycine, serine, and threonine. The addition of glycine to the high methionine diet effectively suppressed the enhancement of the hepatic methionine level and almost completely restored the glycine level, but it only partially restored the serine level and further decreased the threonine level. From these results, it is suggested that the alleviating effect of dietary glycine on methionine toxicity is primarily elicited by the restoration of the hepatic glycine level rather than by an increase in hepatic enzyme activity.
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PMID:Effect of dietary glycine on methionine metabolism in rats fed a high-methionine diet. 366

An international questionnaire survey has been conducted to define better the natural history of homocystinuria due to cystathionine beta-synthase deficiency and permit evaluation of treatment. Data were compiled for 629 patients. Among patients not discovered by newborn screening, B6-responsive individuals on the average have significantly better mental capabilities (mean IQ, 79) than do B6-nonresponsive individuals (mean IQ, 57). Time-to-event curves are presented for the other major clinical abnormalities produced by this disease. Each occurred at significantly lower rates in untreated B6-responsive than in untreated B6-nonresponsive patients, as shown by the following examples: (1) dislocation of optic lenses (at age 10, chances of dislocation: 55% and 82%, respectively); (2) initial clinically detected thromboembolic events (at age 15, chances of having had such an event: 12% and 27%, respectively); (3) radiologic detection of spinal osteoporosis (at age 15, chances of such osteoporosis having been detected: 36% and 64%, respectively); and (4) mortality (at age 30, chances of not surviving: 4% and 23%, respectively). Methionine restriction initiated neonatally prevented mental retardation, retarded the rate of lens dislocation, and may have reduced the incidence of seizures. Pyridoxine treatment of late-detected B6-responsive patients retarded the rate of occurrence of initial thromboembolic events. Following 586 surgical procedures, 25 postoperative thromboembolic complications occurred, six of which were fatal. Reproductive histories were reported predominantly for B6-responsive patients. Living offspring of either men or women patients had few abnormalities. The evidence is inconclusive whether untreated maternal cystathionine beta-synthase deficiency leads to excessive fetal loss. Only 13% of patients detected in screening programs of newborns and classified as to B6-responsiveness were B6-responsive, compared to 47% among late-detected patients. Current screening programs that identify neonatal hypermethioninemia may be preferentially failing to detect B6-responsive patients.
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PMID:The natural history of homocystinuria due to cystathionine beta-synthase deficiency. 387 65

Pyridoxine metabolism is summarised and speculation on possible defects leading to disease is made. Inherited deficiencies of PLP enzymes, which are known to respond in vivo to pharmacologic doses of pyridoxine are listed. The mechanism of pyridoxine responsiveness in homocystinuria due to cystathionine beta-synthase deficiency is discussed. There is a correlation in most (but not all) cases between the presence of residual CS activity, which is often stimulated by pyridoxal phosphate much more than control enzyme, in cultured fibroblasts and pyridoxine responsiveness in vivo. Exceptional patients have been found and are discussed in the light of more detailed studies on their cell lines. Clearly defined abnormalities of pyridoxal phosphate binding to mutant enzyme have been demonstrated and evidence of reduced intracellular stability of mutant CS and possible modulation by pyridoxal phosphate is presented. Preliminary findings suggest that the tissue level of pyridoxal phosphate achieved following pyridoxine treatment could be one other factor in determining pyridoxine responsiveness.
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PMID:Recent advances in the mechanism of pyridoxine-responsive disorders. 393 Aug 45

Homocystinuria due to cystathionine beta-synthase deficiency may be responsive to pyridoxine, a precursor of the cofactor pyridoxal phosphate, and the amount of residual enzyme activity present is the probable determinant of this. In six treated pyridoxine-responsive patients whose biochemical control of fasting plasma amino acid levels appeared optimal, we assessed the effects on plasma amino acids of standard oral methionine loads (4g/m2 of body area) before and after adding betaine (trimethylglycine) 6 g/d, to the treatment regimen of pyridoxine and folic acid. Our aim was to define the capacity of these patients to metabolize methionine and to determine whether betaine would effect a reduction in postload homocysteine levels. During the 24 hours after the methionine challenge all patients had higher plasma methionine and homocysteine and lower cysteine than did 17 normal subjects. After betaine these homocysteine responses were reduced to near normal, and there was a trend toward increased methionine. There was a direct correlation between premethionine fasting homocysteine and mean homocysteine responses during the 24 hours following the methionine load, both before (r = 0.79) and after betaine (r = 0.71). Betaine also increased plasma cysteine levels in patients with the more severe biochemical abnormalities. After betaine there were modest increases in plasma serine (mean increase 25%; P less than 0.025). Since the vascular complications of homocystinuria are related to increased plasma homocysteine, betaine therapy may reduce this risk in patients receiving a standard pyridoxine and folic acid regimen in whom there are abnormal homocysteine responses after a standard methionine load.
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PMID:Homocystinuria due to cystathionine beta-synthase deficiency--the effects of betaine treatment in pyridoxine-responsive patients. 393 99

It has been shown that yeast tryptophan synthase (L-serine hydro-lyase (adding indoleglycerol-phosphate) EC 4.2.1.20) catalyses tritium exchange reactions between protons on the alpha-carbon of L-serine of L-tryptophan, and water. The absolute rates of these reactions and indole-serine condensation (reaction B), all of which are pyridoxal phosphate-dependent, were measured. L-Serine exchange was resolved into two components, a high-affinity, slow, Michaelian reaction (KmS,H = 0.06 mM, kcats,H 3 X 10(-3) s-1) and a faster reaction (kcat greater than 2.5 S-1) which was not saturated even at 100 mM L-serine. Hydrogen exchange by tryptophan was a Michaelian process (KmT,H = 2.9 mM; kcatT,H = 0.6 s-1). Indole did not inhibit either exchange reaction. A plausible explanation of the results, that reaction B has a ping-pong mechanism with serine as first substrate and water and L-tryptophan as first and second products, respectively, was inadequate because of the observations that L-tryptophan is as first and second products, respectively, was inadequate because of the observations that L-tryptophan is synthesised with less than 1 mol of exchanged proton per mol amino acid, and that the ratio kcat/Km for serine changes between enzyme reactions. A branched modification with two enzyme-serine complexes, only one of which will exchange protons with water, will fit all the results.
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PMID:Hydrogen exchange kinetics and the mechanism of reaction B of yeast tryptophan synthase. 393 73

The contents of cystathionine and taurine, as well as cystathionine beta-synthase activity in various regions of the brains of normal and DL-propargylglycine-treated rats, were measured. The content of cystathionine in each region of brain increased gradually from 0.5 mg to 20 mg/200 g body weight in relation to the dose of DL-propargylglycine. Cystathionine was found to be unevenly distributed in brains of both normal and DL-propargylglycine-treated rats. On the other hand, the activity of cystathionine beta-synthase was evenly distributed in various regions of normal rat brain, and was unaltered following treatment of rats with DL-propargylglycine. The concentration of taurine was similarly unaffected by DL-propargylglycine injection.
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PMID:Cystathionine accumulation in various regions of brain of DL-propargylglycine-treated rats. 397 10

Cystathionine accumulated in several tissues of dams and fetuses by a single intraperitoneal administration of L-proparglyglycine to pregnant rats. Cystathionine in the liver of dams reached its maximal level at about 15 hrs after L-proparglyglycine injection (10 mg/300g), while that in the kidney and brain of dams, and in the liver, kidney, and brain of fetuses reached a maximum at about 21 hrs. The content of cystine in the liver of fetuses decreased gradually in proportion to the amount of L-proparglyglycine administered. Cystathionine gamma-lyase activity in the liver of dams and fetuses decreased to about 2-4% of that of control rats at 15 hrs after L-proparglyglycine injection, and that in the kidney and pancreas of dams to about 10-20% of that of control rats. On the other hand, cystathionine beta-synthase activity did not show significant changes from that of control rats.
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PMID:Effect of L-propargylglycine on metabolism of sulfur-containing amino acids in pregnant rats and their fetuses. 399 31


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