Disease relevance of Cbs

• Treatment with insulin also decreased CBS levels in HepG2 cells, a human hepatoma cell line [1].
• Vitamin B-6 deficiency in rats reduces hepatic serine hydroxymethyltransferase and cystathionine beta-synthase activities and rates of in vivo protein turnover, homocysteine remethylation and transsulfuration [2].
• These studies also showed no correlation of the MTHFR and CBS enzymes with plasma homocysteine levels or intimal hyperplasia [3].
• Homocystinuria is an inborn error of metabolism caused by severe deficiency of cystathionine beta-synthase activity [4].
• Whereas mRNA levels of cystathionine beta-synthase remained unaltered, deficiency reduced the enzyme activity (48.7 +/- 2.9 versus 83.6 +/- 6.3 nmol/h/mg, p < 0.01), an effect potentiated by hypoxia (29.4 +/- 4.7 nmol/h/mg, p < 0.05) [5].

High impact information on Cbs

• There was a significant decline in homocysteine concentrations in diabetic rats, owing in part to a 38% increase in the abundance of the transsulfuration enzyme cystathionine beta-synthase; treatment of diabetic rats with RA prevented cystathionine beta-synthase induction [6].
• Cystathionine beta-synthase (CBS), a key enzyme involved in the transsulfuration pathway, which irreversibly converts homocysteine to cysteine, catalyzes the condensation of serine and homocysteine to cystathionine [1].
• Studies in streptozotocin-induced diabetic rats have shown that CBS enzyme activity is elevated in the liver but not in the kidney, and this effect is reversed by insulin treatment [1].
• Nuclear run-on experiments in the rat cells confirmed that stimulation of CBS gene expression by glucocorticoids and the inhibition by insulin occurred at the transcriptional level [1].
• Hepatic concentrations of S-adenosylmethionine and S-adenosylhomocysteine, allosteric activators of cystathionine beta-synthase, were also increased following glucagon treatment [7].

Biological context of Cbs

• Rat cystathionine beta-synthase. Gene organization and alternative splicing [8].
• cDNA clones coding for hemoprotein H-450 were isolated from a rat liver cDNA library using anti-H-450 antibody [9].
• The parasite has an active cystathionine-beta-synthase and, as in other tissues, this enzyme has a wide substrate specificity [10].
• The amounts of CSE and CBS in testes did not alter in response to administration of cadmium chloride, an antispermatogenic stressor leading to apoptosis [11].
• Development of methionine synthase, cystathionine-beta-synthase and S-adenosyl-homocysteine hydrolase during gestation in rats [12].

Anatomical context of Cbs

• Flux through cystathionine beta-synthase was increased 5-fold in hepatocytes isolated from glucagon-treated rats as determined by production of (14)CO(2) and alpha-[1-(14)C]ketobutyrate from l-[1-(14)C]methionine [7].
• We found that CBS and CSE are expressed in the colon and spinal cord [13].
• Immunohistochemistry revealed distinct distribution of the two enzymes: CBS occurred mainly in Leydig cells and was also detectable in Sertoli cells and germ cells, whereas CSE was evident in Sertoli cells and immature germ cells involving spermatogonia [11].
• The contents of cystathionine and taurine, as well as cystathionine beta-synthase activity, in various cerebellar regions and pineal body of normal and DL-propargylglycine-treated rats were measured [14].
• In embryonic and fetal tissue cystathionine-beta-synthase first occurred in fetal liver [12].

Associations of Cbs with chemical compounds

• Cystathionine beta-synthase, however, did not catalyze direct formation of selenocysteine from serine and H2Se [15].
• Thus, selenocysteine is synthesized from selenohomocysteine and cystathionine beta-synthase and cystathionine gamma-lyase reactions [15].
• CBS activity, assayed in the presence or absence of added S-adenosylmethionine, was independent of diet type and PN level [16].
• To assess relations between vitamin B-6 and transsulfuration, we evaluated the effects of dietary pyridoxine (PN) on the hepatic concentration of relevant metabolites and in vitro activity of CBS and CGL [16].
• 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 [17].

Other interactions of Cbs

• We have investigated selenocysteine (2-amino-3-hydroselenopropionic acid) synthesis with cystathionine beta-synthase (EC 4.2.1.22) and cystathionine gamma-lyase (EC 4.4.1.1) of rat liver [15].
• In the control system, 5-methyltetrahydrofolate homocysteine methyltransferase, betaine homocysteine methyltransferase, and cystathionine beta-synthase accounted for 27, 27, and 46%, respectively, of the homocysteine consumed [18].
• Like AdoMet, S-adenosylethionine is an activator of cystathionine beta-synthase and will effectively promote the catabolism of homocysteine through cystathionine synthesis [19].

Analytical, diagnostic and therapeutic context of Cbs

• In H4IIE cells, a rat hepatoma cell culture model, glucocorticoids increased the cellular levels of CBS enzyme protein and CBS mRNA; insulin inhibited this stimulatory effect [1].
• Molecular cloning and sequence analysis of cDNA coding for rat liver hemoprotein H-450 [9].
• The effect of concentrations of sulfur-containing amino acids, activities of cystathionine gamma-lyase and cystathionine beta-synthase, and level of vitamin B6 were examined following menthionine administration in normal rats and chronically uremic rats with 7/8 nephrectomy [20].
• Hepatic gamma-cystathionase activity at 12 h after the intraperitoneal injection decreased in proportion to the amount of D,L-propargylglycine administered, but hepatic cystathionine beta-synthase activity did not change [21].
• OBJECTIVE: The effect of a rat carotid endarterectomy (CEA) on homocysteine and the metabolic enzymes methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS) was studied [22].

References