Origin of Elevated S-Glutathionylated GAPDH in Chronic Neurodegenerative Diseases.

ABSTRACT: H₂O₂-oxidized glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalytic cysteine residues (C_c(SH) undergo rapid S-glutathionylation. Restoration of the enzyme activity is accomplished by thiol/disulfide S_N2 displacement (directly or enzymatically) forming glutathione disulfide (G(SS)G) and active enzyme, a process that should be facile as C_c(SH) reside on the subunit surface. As S-glutathionylated GAPDH accumulates following ischemic and/or oxidative stress, in vitro/silico approaches have been employed to address this paradox. C_c(SH) residues were selectively oxidized and S-glutathionylated. Kinetics of GAPDH dehydrogenase recovery demonstrated that glutathione is an ineffective reactivator of S-glutat

SUBMITTER: Hyslop PA 

PROVIDER: S-EPMC10056234 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature