Advertisement

 

 

Identification of a metabolic disposal route for the oncometabolite-(2-succino)cysteine in.

Identification of a metabolic disposal route for the oncometabolite-(2-succino)cysteine in.
Author Information (click to view)

Niehaus TD, Folz J, McCarty DR, Cooper AJL, Moraga Amador D, Fiehn O, Hanson AD,


Niehaus TD, Folz J, McCarty DR, Cooper AJL, Moraga Amador D, Fiehn O, Hanson AD, (click to view)

Niehaus TD, Folz J, McCarty DR, Cooper AJL, Moraga Amador D, Fiehn O, Hanson AD,

Advertisement

The Journal of biological chemistry 2018 04 06() pii jbc.RA118.002925
Abstract

Cellular thiols such as cysteine spontaneously and readily react with the respiratory intermediate fumarate, resulting in the formation of stable-(2-succino)-adducts. Fumarate-mediated succination of thiols increases in certain tumors and in response to glucotoxicity associated with diabetes. Therefore,-(2-succino)-adducts such as-(2-succino)cysteine (2SC) are considered oncometabolites and biomarkers for human disease. No disposal routes for-(2-succino) compounds have been reported prior to this study. Here, we show thatmetabolizes 2SC to cysteine using a pathway encoded by theoperon. The first step is-acetylation of 2SC, followed by an oxygenation that we propose results in the release of oxaloacetate and-acetylcysteine, which is deacetylated to give cysteine. Knockouts of the genes predicted to mediate each step in the pathway lose the ability to grow on 2SC as the sulfur source and accumulate the expected upstream metabolite(s). We further show that-acetylation of 2SC relieves toxicity. This is the first demonstration of a metabolic disposal route for any-(2-succino)-compound, paving the way towards the identification of corresponding pathways in other species.

Submit a Comment

Your email address will not be published. Required fields are marked *

1 × 4 =

[ HIDE/SHOW ]