Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.1.22 (cystathionine beta-synthase)
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There is as yet no satisfactory experimental model for homocystinuria due to cystathionine beta-synthase deficiency. We produced homocysteinemia in pigs for up to 60 days by continuously infusing DL-homocysteine thiolactone and compared the changes in the plasma amino acids with the findings in 16 patients with homocystinuria. Vascular morphology was also investigated in the infused animals. In six pigs DL-homocysteine thiolactone, 0.68/kg/day for 13-60 days increased mean levels of methionine from 43.6 to 116.6 mumole/l, homocystine from zero to 67.4, cysteine-homocysteine disulfide from 4.3 to 49.2, taurine from 97.3 to 193.9 and alpha-amino-n-butyric acid from 16.5 to 147.4. Total cysteine did not change although cystine decreased from 50.8 to 26.2 mumole/liter. There were no amino acid changes in four saline infused (control) pigs and no differences in vascular morphology between experimental and control animals. Seven severely affected homocystinuric patients, biochemically, unresponsive to pyridoxine administration, had plasma sulfur-containing amino acid changes of similar magnitude to those in the infused pigs except that taurine concentrations were normal and total cysteine was decreased as it also was in nine pyridoxine responsive patients. In contrast to the pigs, plasma alpha-amino-n-butyric acid was normal in all 16 patients. We conclude that this model provides information about methionine metabolism but that it should be used with caution to study mechanisms in homocystinuria because it does not exactly mimic the human disease and because the thiolactone, which at present must be used as the source of infused L-homocysteine, itself produces changes which could influence results.
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PMID:Experimental homocysteinemia in pigs: comparison with studies in sixteen homocystinuric patients. 709 48

Butyrate is a short-chain fatty acid that arrests growth of various types of cells. H(2)S can be endogenously produced by cystathionine gamma-lyase (CSE) or cystathionine beta-synthase (CBS) or both in colonic tissues. In this study, we observed endogenous H(2)S production in a colon cancer cell line (WiDr) and colonic tissues through the activity of both CSE and CBS. After 24 h of incubation of WiDr cells, butyrate increased cell production of H(2)S and upregulated CBS and CSE expressions. Both butyrate and NaHS (a H(2)S donor) decreased cell viability in a dose-dependent manner. Blockade of CBS, but not CSE, decreased butyrate-stimulated H(2)S production and reversed butyrate-inhibited cell viability. In addition, NaHS treatment stimulated the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), but not c-Jun N-terminal kinase (JNK). Inhibition of the phosphorylation of either p38 MAPK or ERK did not abolish NaHS-induced cell death. Butyrate treatment increased the phosphorylation of ERK, not p38 MAPK and JNK, but inhibition of ERK and p38 MAPK phosphorylation did not inhibit butyrate-reduced cell viability. In conclusion, butyrate regulates endogenous H(2)S production by stimulating CBS expression in colon cancer cells, but butyrate and H(2)S inhibit cancer cell growth through different mechanisms.
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PMID:Butyrate-stimulated H2S production in colon cancer cells. 1980 45