Premium
Physiological significance of persulfide generation by the transsulfuration pathway
Author(s) -
Yadav Pramod Kumar,
Martinov Michael,
Vitvitsky Victor,
Seravalli Javier,
Wedmann Rudolf,
Filipovic Milos R,
Banerjee Ruma
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.765.13
Subject(s) - cystathionine beta synthase , cysteine , chemistry , homocysteine , transsulfuration , cystine , serine , methionine , biochemistry , sulfurtransferase , cystathionine gamma lyase , polysulfide , enzyme , amino acid , electrode , electrolyte
In mammalian cells, cystathionine β‐synthase (CBS), cystathionine γ‐lyase (CSE) and merceptopyruvate sulfurtransferase (MST) catalyze H 2 S synthesis. Of these three enzymes, CBS is regulated by an unusual heme which is responsive to the gaseous signaling molecules, CO and NO. CBS also catalyzes the condensation of homocysteine and serine to form cystathionine, which is further utilized by CSE to generate cysteine. H 2 S plays an important role in various physiological process, acting as a neuromodulator, vasorelaxant, cardioprotective agent, and has anti‐inflammatory effects. H 2 S signals by posttranslational modification of reactive cysteine thiols to persulfides. Recently it has been shown that CBS and CSE can synthesize cysteine persulfide (Cys‐SSH) using cystine as a substrate. In fact, it was reported that Cys‐SSH rather than H 2 S is the major product of CBS and CSE. However, the intracellular milieu is reducing and the availability of cystine is limiting. In the present study, we examined the kinetics of Cys‐SSH and homocysteine persulfide formation and of Cys‐SSH decay. We also evaluated the effect of increased cellular cystine on persulfide and polysulfide levels and simulated the relative rates of H 2 S and Cys‐SSH biogenesis at physiologically relevant substrate concentrations. Support or Funding Information This work was supported by a grant from the National Institutes of Health (HL58984 to RB) and the American Heart Association (14POST18760003 to PKY).