Yashvi Shukla
Research Mentor(s): Ruma Banerjee
Mentor Department: Biological Chemistry
Authors: Yashvi Shukla, Joseph Roman, Ruma Banerjee
Session: Session 5 (2:00pm – 2:50pm)
Presentation Type: Poster 103
Abstract
Sulfide quinone oxidoreductase (SQOR) detoxifies hydrogen sulfide (H2S), an endogenously-produced gas, which inhibits cellular respiration. SQOR contains both flavin adenine dinucleotide and a trisulfide cofactor consisting of three covalently bonded sulfur atoms. The trisulfide cofactor is essential to catalysis, which leads to the oxidation of H2S to glutathione persulfide in the presence of glutathione. The SQOR-catalyzed reaction represents the first step in the mitochondrial sulfide oxidation pathway, and concomitantly leads to reduction of coenzyme Q (CoQ) to CoQH2, which is accompanied by a decrease in absorbance at 278 nm (Δε=11000 M-1 cm-1). To identify the source of the bridging sulfur in the novel trisulfide cofactor in SQOR, HT-29 cells (human colorectal adenocarcinoma) were grown in the presence of propargylglycine (PPG) an inhibitor of gamma-cystathionase, low cystine, and/or buthionine sulfoximine (BSO) an inhibitor of glutathione synthesis, and the SQOR activity was measured. While PPG and low cystine decreased SQOR activity (16.3 nmolmg-1min-1) compared to untreated controls (26.3 nmolmg-1min-1), BSO increased activity (33.9 nmolmg-1min-1). Similar effects were observed in the human endothelial cell line EA.hy 926. However, while EA.hy 926 cells died when cultured in low cystine conditions with BSO and PPG, HT–29 cells did not. Though the mechanism for trisulfide installation requires further elucidation, our data suggest cysteine persulfide as a likely source of sulfane sulfur, which is generated from cystine by gamma-cystathionase.
