A kinetic model of the system: Tyrosyl radical-nitrogen oxide-superoxide ion

It is generally recognized that the initial step in the formation of athero sclerotic plaque in humans involves the peroxidation of low density lipopro teins (LDL). However, there is no agreement on the mechanism that initiates peroxidation. Among the candidates are several that involve tyrosyl radica l, nitrogen oxide, and superoxide ion or their mutual reaction products. In this paper a kinetic model of this system is constructed that examines the nature of these reactions, and places some constraints on their possible o verall contribution to the initiation of peroxidation. The reversible react ion of nitric oxide and tyrosyl radical acts to "buffer" tyrosyl radical co ncentrations while the reaction of tyrosyl radical with superoxide ion scav enges tyrosyl radical. Quantitatively, the reaction of nitric oxide with su peroxide to form peroxynitrite is a more important process, but the physiol ogical significance would appear to be related to details of the decay of p eroxynitrite that are still in dispute. (C) 1999 Academic Press.