Vitamin B-6 nutritional status and cellular availability of pyridoxal 5 '-phosphate govern the function of the transsulfuration pathway's canonical reactions and hydrogen sulfide production via side reactions

作者：Gregory Jesse F^*; DeRatt Barbara N; Rios Avila Luisa; Ralat Maria; Stacpoole Peter W

来源：Biochimie, 2016, 126: 21-26.

DOI：10.1016/j.biochi.2015.12.020

• One-carbon metabolism
• Transsulfuration
• Cystathionine beta-synthase
• Cystathionine gamma-lyase
• Lanthionine
• Homolanthionine
• Hydrogen sulfide
• Vitamin B-6

The transsulfuration pathway (TS) acts in sulfur amino acid metabolism by contributing to the regulation of cellular homocysteine, cysteine production, and the generation of H2S for signaling functions. Regulation of TS pathway kinetics involves stimulation of cystathionine beta-synthase (CBS) by S-adenosylmethionine (SAM) and oxidants such as H2O2, and by Michaelis Menten principles whereby substrate concentrations affect reaction rates. Although pyridoxal phosphate (PLP) serves as coenzyme for both CBS and cystathionine gamma-lyase (CSE), CSE exhibits much greater loss of activity than CBS during PLP insufficiency. Thus, cellular and plasma cystathionine concentrations increase in vitamin B-6 deficiency mainly due to the bottleneck caused by reduced CSE activity. Because of the increase in cystathionine, the canonical production of cysteine (homocysteine -> cystathionine -> cysteine) is largely maintained even during vitamin B-6 deficiency. Typical whole body transsulfuration flux in humans is 3-7 mu mol/h per kg body weight.
The in vivo kinetics of H2S production via side reactions of CBS and CSE in humans are unknown but they have been reported for cultured HepG2 cells. In these studies, cells exhibit a pronounced reduction in H2S production capacity and rates of lanthionine and homolanthionine synthesis in deficiency. In humans, plasma concentrations of lanthionine and homolanthionine exhibit little or no mean change due to 4-wk vitamin B-6 restriction, nor do they respond to pyridoxine supplementation of subjects in chronically low-vitamin B-6 status. Wide individual variation in responses of the H2S biomarkers to such perturbations of human vitamin B-6 status suggests that the resulting modulation of H2S production may have physiological consequences in a subset of people.

• 出版日期2016-7