Conversion of NO2 to NO by reduced coenzyme F420 protects mycobacteria from nitrosative damage.

Abstract

In mycobacteria, F(420), a deazaflavin derivative, acts as a hydride transfer coenzyme for an F(420)-specific glucose-6-phosphate dehydrogenase (Fgd). Physiologically relevant reactions in the mycobacteria that use Fgd-generated reduced F(420) (F(420)H(2)) are unknown. In this work, F(420)H(2) was found to be oxidized by NO only in the presence of oxygen. Further analysis demonstrated that NO(2), produced from NO and O(2), was the oxidant. UV-visible spectroscopic and NO-sensor-based analyses proved that F(420)H(2) reduced NO(2) to NO. This reaction could serve as a defense system for Mycobacterium tuberculosis, which is more sensitive to NO(2) than NO under aerobic conditions. Activated macrophages produce NO, which in acidified phagosomes is converted to NO(2). Hence, by converting NO(2) back to NO with F(420)H(2), M. tuberculosis could decrease the effectiveness of antibacterial action of macrophages; such defense would correspond to active tuberculosis conditions where the bacterium grows aerobically. This hypothesis was consistent with the observation that a mutant strain of Mycobacterium smegmatis, a nonpathogenic relative of M. tuberculosis, which either did not produce or could not reduce F(420), was approximately 4-fold more sensitive to NO(2) than the wild-type strain. The phenomenon is reminiscent of the anticancer activity of gamma-tocopherol, which reduces NO(2) to NO and protects human cells from NO(2)-induced carcinogenesis.

• Authors: Endang Purwantini, Biswarup Mukhopadhyay
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 106 Issue 15 Pg. 6333-8 (Apr 14 2009) ISSN: 1091-6490 [Electronic] United States
• PMID: 19325122 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitrogen Oxides
• factor 420
• Nitrogen Dioxide
• Riboflavin

Topics

• Mycobacterium tuberculosis (metabolism)
• Nitrogen Dioxide (metabolism)
• Nitrogen Oxides (metabolism)
• Oxidation-Reduction
• Riboflavin (analogs & derivatives, chemistry, metabolism)
• Spectrophotometry
• Stress, Physiological