Nitrosative stress: Metabolic pathway involving the flavohemoglobin

Alfred Hausladen, Andrew J. Gow, Jonathan S. Stamler

Research output: Contribution to journalArticle

236 Citations (Scopus)

Abstract

Nitric oxide (NO) biology-has focused on the tightly regulated enzymatic mechanism that transforms L-arginine into a family of molecules, which serve both signaling and defense functions. However, very little is known of the pathways that metabolize these molecules or turn off the signals. The paradigm is well exemplified in bacteria where S-nitrosothiols (SNO) - compounds identified with antimicrobial activities of NO synthase - elicit responses that mediate bacterial resistance by unknown mechanisms. Here we show that Escherichia coli possess both constitutive and inducible elements for SNO metabolism. Constitutive enzyme(s) cleave SNO to NO whereas bacterial hemoglobin, a widely distributed flavohemoglobin of poorly understood function, is central to the inducible response. Remarkably, the protein has evolved a novel heme-detoxification mechanism for NO. Specifically, the heme serves a dioxygenase function that produces mainly nitrate. These studies thus provide new insights into SNO and NO metabolism and identify enzymes with reactions that were thought to occur only by chemical means. Our results also emphasize that the reactions of SNO and NO with hemoglobins are evolutionary conserved, but have been adapted for cell-specific function.

Original languageEnglish
Pages (from-to)14100-14105
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number24
DOIs
Publication statusPublished - 24 Nov 1998
Externally publishedYes

Fingerprint

S-Nitrosothiols
Metabolic Networks and Pathways
Nitric Oxide
Heme
Dioxygenases
Enzymes
Nitric Oxide Synthase
Nitrates
Arginine
Hemoglobins
Escherichia coli
Bacteria
Proteins

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Nitrosative stress : Metabolic pathway involving the flavohemoglobin. / Hausladen, Alfred; Gow, Andrew J.; Stamler, Jonathan S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 24, 24.11.1998, p. 14100-14105.

Research output: Contribution to journalArticle

Hausladen, Alfred ; Gow, Andrew J. ; Stamler, Jonathan S. / Nitrosative stress : Metabolic pathway involving the flavohemoglobin. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 24. pp. 14100-14105.
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