Vitamin B6 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

Biochimie
Jesse F GregoryPeter W Stacpoole

Abstract

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 β-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 γ-lyase (CSE), CSE exhibits much greater loss of activity than CBS during PLP insufficiency. Thus, cellular and plasma cystathionine concentrations increase in vitamin B6 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 B6 deficiency. Typical whole body transsulfuration flux in humans is 3-7 μmol/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 produ...Continue Reading

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Citations

Sep 7, 2016·Molecular Aspects of Medicine·Per Magne UelandArve Ulvik
Apr 11, 2018·Antioxidants & Redox Signaling·Christopher HineJames R Mitchell
Oct 1, 2020·Molecular Medicine·Maurizio Dattilo
Dec 30, 2020·Antioxidants & Redox Signaling·Peter RoseYi-Zhun Zhu
Dec 6, 2020·Nutrients·Rafael Martín-MasotTeresa Nestares
Mar 7, 2021·International Journal of Molecular Sciences·Yi-Zhen WangDong-Dong Wu
Apr 4, 2021·Journal of Clinical Medicine·Mikkel Parsberg WergeLise Lotte Gluud
Apr 3, 2021·Frontiers in Aging Neuroscience·Bindu Diana Paul
May 25, 2021·Journal of Alzheimer's Disease : JAD·Hui HanHaimin Chen

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