Nitric oxide-induced S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase inhibits enzymatic activity and increases endogenous ADP-ribosylation

Luis Molina Y Vedia*, Brad McDonald, Bryan Reep, Bernhard Brüne, Mauricio Di Silvio, Timothy R. Billiar, Eduarde G. Lapetina

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

384 Scopus citations

Abstract

Using conditions that produced chronic inflammation in rat liver, we were able to find a correlation between induction of nitric oxide production and inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12). This enzyme is a tetramer composed of identical Mr 37,000 subunits. The tetramer contains 16 thiol groups, four of which are essential for enzymatic activity. Our information indicates that four thiol groups are S-nitrosylated by exposure to authentic nitric oxide (NO) gas. Furthermore, NO decreased GAPDH activity while increasing its auto-ADP-ribosylation. Reduced nicotinamide adenine dinucleotide and dithiothreitol are required for the S-nitrosylation of GAPDH caused by the NO-generating compound sodium nitroprusside. Our results suggests that a new and important action of nitric oxide on cells is the S-nitrosylation and inactivation of GAPDH S-Nitrosylation of GAPDH may be a key covalent modification of multiple regulatory consequences in chronic liver inflammation.

Original languageEnglish
Pages (from-to)24929-24932
Number of pages4
JournalJournal of Biological Chemistry
Volume267
Issue number35
StatePublished - 15 Dec 1992
Externally publishedYes

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