期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 491, 期 1-2, 页码 96-105出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2009.08.022
关键词
Cystathionine beta-synthase; Heme; Pyridoxal 5 '-phosphate; Peroxynitrite; Nitrotyrosine; Nitrotryptophan; Homocysteine; Hyperhomocysteinemia
资金
- CSIC (Universidad de la Republica, Uruguay)
- Uruguayan Research Council
- Programa para el Desarrollo de las Ciencias Basicas (PEDECIBA, Uruguay)
- National Institutes of Health [HL58984]
Cystathionine beta-synthase (CBS) is a homocysteine metabolizing enzyme that contains pyridoxal phosphate (PLP) and a six-coordinate heme cofactor of unknown function. CBS was inactivated by peroxynitrite, the product of nitric oxide and superoxide radicals. The IC50 Was similar to 150 mu M for 5 mu M ferric CBS. Stopped-flow kinetics and competition experiments showed a direct reaction with a second-order rate constant of (2.4-5.0) x 10(4) M-1 s(-1) (pH 7.4, 37 degrees C). The radicals derived from peroxynitrite, nitrogen dioxide and carbonate radical, also inactivated CBS. Exposure to peroxynitrite did not modify bound PLP but led to nitration of Trp208, Trp43 and Tyr223 and alterations in the heme environment including loss of thiolate coordination, conversion to high-spin and bleaching, with no detectable formation of oxoferryl compounds nor promotion of one-electron processes. This study demonstrates the susceptibility of CBS to reactive oxygen/nitrogen species, with potential relevance to hyperhomocysteinemia, a risk factor for cardiovascular diseases. (C) 2009 Elsevier Inc. All rights reserved.
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