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Coenzyme A Persulfide Prioritizes Sulfide over Butyrate Oxidation
Author(s) -
Landry Aaron P.,
Ballou David P.,
Banerjee Ruma
Publication year - 2019
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.2019.33.1_supplement.633.15
Subject(s) - butyrate , biochemistry , cofactor , electron acceptor , chemistry , mitochondrion , sulfur , sulfide , redox , oxidoreductase , dehydrogenase , enzyme , organic chemistry , fermentation
The human gut microbiota metabolizes fiber remnants from the diet to produce large quantities of butyrate, the primary energy source for colonic epithelial cells. In the mitochondria of these cells, short‐chain acyl‐CoA dehydrogenase (ACADS) is a flavoenzyme that catalyzes the initial step of butyrate oxidation and relays the resulting electrons to the coenzyme Q 10 pool. When ACADS is isolated from native or recombinant sources, a vibrant green color is observed in the protein that corresponds to a charge transfer complex between the FAD cofactor and coenzyme A persulfide (CoASSH). The CoASSH‐bound form of ACADS is enzymatically inactive, and previous studies demonstrated that butyrate oxidation is impaired in colonocytes exposed to hydrogen sulfide (H 2 S), suggesting that CoASSH may be generated under these conditions. H 2 S is produced at high concentrations by sulfate‐reducing bacteria in the colon, and its toxic accumulation is prevented by sulfide quinone oxidoreductase (SQR), a mitochondrial membrane‐bound flavoenzyme that oxidizes H 2 S to a persulfide with concomitant reduction of coenzyme Q 10 . SQR is remarkably promiscuous, and is capable of transferring the sulfane sulfur from H 2 S oxidation to a number of low molecular weight thiol acceptors. We thus hypothesized that the source of CoASSH, and therefore ACADS inhibition, is H 2 S oxidation via SQR activity utilizing CoA as an acceptor. We demonstrated that CoA was a competent small molecule sulfur acceptor using the steady‐state SQR assay, while the kinetics of sulfur transfer from H 2 S to CoA were characterized using stopped flow spectroscopy. CoASSH generated in situ by SQR led to a charge transfer complex in ACADS, providing further evidence that CoASSH is the persulfide product of the SQR reaction. As both ACADS and SQR relay electrons to coenzyme Q 10 , competition over the coenzyme Q 10 substrate would inhibit the effective clearance of the respiratory toxin, H 2 S. These studies implicate the inhibition of ACADS by CoASSH as a potential modulatory mechanism to prioritize sulfide clearance by reserving the coenzyme Q 10 pool for SQR. Support or Funding Information This work was supported in part by the National Institutes of Health (GM112455 to Ruma Banerjee and F32GM122357 to Aaron P. Landry). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .