ANNUAL REVIEWS

Further

Quick links to online content Copyright 1973, All rights reserved

Annu. Rev. Biochem. 1975.44:147-159. Downloaded from www.annualreviews.org by Pennsylvania State University on 06/08/12. For personal use only.

SUPEROXIDEDISMUTASES

:877

Irwin Fridovich Departmentof Biochemistry,DukeUniversity MedicalCenter, Durham, North Carolina 27710

CONTENTS INTRODUCTION ................................................................. SUPEROXIDE RADICAL AND THE DISMUTATION REACTIONS .................. ASSAYSFOR SUPEROXIDE DISMUTASEACTIVITY ............................... BIOLOGICAL IMPORTANCE OF SUPEROXIDE DISMUTASE ...................... VARIETIES OF SUPEROXIDEDISMUTASES....................................... Copper- and Zinc-Containing Superoxide Dismutases ..................................... Manganese-Containin 9 Superoxide Dismutases ........................................... Iron-Containing Superoxide Dismutases ................................................. POLEMICS....................................................................... SUMMARY ANDSPECULATIONS.................................................

147 148 149 149 151 151 152 153 t 53 155

INTRODUCTION Thereis a bizarre enzymaticactivity universally present in respiring cells. Thesubstrate is an unstable free radical that can be present only in minuscule amounts at any instant, and the reaction catalyzed proceeds at a rapid rate even in the absence of the enzyme.Yet the enzymeis essential for the survival of aerobic cells. It catalytically scavenges the superoxide radical, whichappears to be an important agent of the toxicity of oxygen, and thus provides a defense against this aspect of oxygen toxicity. The reaction whose rate it enhances is a disproportionation or dismutation of these radicals and maybe written 02

+02

+2H ~ --~ 2

H202+O

This activity was discoveredonly recently (1, 2) and, given the instability of O~, it is not surprising that this finding waslong delayedand finally achievedby following chance observations rather than by design. During the past few years there has been a surge of interest in this enzymaticactivity and a voluminousliterature has accumulated.This is an intellectually exciting situation but it puts the reviewer in an unenviable position. Thus it is clear that the continued rapid appearance of new

148 FRIL)OVICH Nevertheless, the attempt must be made. Hopefully this review will carry the story a bit further than did its predecessors(3-7).

Annu. Rev. Biochem. 1975.44:147-159. Downloaded from www.annualreviews.org by Pennsylvania State University on 06/08/12. For personal use only.

SUPEROXIDE

RADICAL

AND THE DISMUTATION

REACTIONS

O~ is a commonintermediate of oxygen reduction. This is a consequence of the fact that molecular oxygenin its ground state prefers univalent pathwaysof reduction. The electronic basis for this preference rests upon a spin restriction, which has been discussed by Taube (8). In any case, a number of reactions of interest to biochemists have been shownto generate O~. Amongthese are the autoxidations of hydroquinones, leucoflavins, and catechol amines (9-16), thiols (17), reduced dyes (9, 18, 19), tetrahydropteridines (20), ferredoxins (21-24), rubredoxin (25), hemoproteins (26-28). Furthermore, the catalytic actions of several enzymes have been shown to evolve O~-. This category includes xanthine oxidase (2, 29, 30), aldehyde oxidase (31, 32), dihydro-orotic dehydrogenase(33), and a group of flavoprotein dehydrogenases(14). In addition, there are several oxidases and hydroxylases inhibited by superoxide dismutase, whichsuggests that O~is an intermediate in their catalytic cycles. These include tryptophan dioxygenase(34), the reconstituted liver microsomalhydroxylase (35), soluble hydroxylases from Aspergillus niger (36), and galactose oxidase (37). Finally, 02 is producedby intact granulocytes during the act of phagocytosis (38-41), by illuminated chloroplasts (42~46), and by lyophilized liver microsomes(47, 48). Thus, although we remain ignorant of the identity of the quantitatively most significant sources of O] within any given type of cell and of the absolute rates of O~production inside cells, we can feel secure in concluding that respiring cells will producesignificant amountsof 0 2. The superoxide radical cannot accumulate in aqueous media because it readily undergoes a disp(oportionation or dismutation reaction. O~ is the conjugate base of a weak acid called the hydroperoxyl radical whose pKa is 4.8. The pH dependence of the spontaneous dismutation can be explained on the basis of this pKa and on the following reactions (49) -1 HO~ +HO~-~ H202 +O =7.6× 10s M-tsec 2 + HO~+O~ +H ~ H202+O2 = 8.5 x 107 -t M-lsec O]+O~+2H +~H202+O 2 -1

Superoxide dismutases.

ANNUAL REVIEWS Further Quick links to online content Copyright 1973, All rights reserved Annu. Rev. Biochem. 1975.44:147-159. Downloaded from www.a...
761KB Sizes 0 Downloads 0 Views