Possible Mechanisms by which Superoxide Brings About Cell Damage and Promotes Lipid Peroxidation

Possible Mechanisms by Which Superoxide Brings About Cell Damage and Promotes Lipid Peroxidation 

A metal ion not infrequently implicated in superoxide-associated damage to cells is Fe . It is known that Fe can form complexes with superoxide, thereby leading to the formation of peroxide or even possibly OH-radicals, which are highly damaging. It is also feasible that damage can result from the interaction of superoxide with other metal ions. Isolated mitochondria swell rapidly when incubated in the presence of Ca. Such cells can be protected for long periods by 10% dimethylsulfoxide, an agent which readily destroys peroxide. Suspensions of liver cells tolerate ischemic 

It is known that superoxide forms complexes with Ca , thereby permitting formation of calcium peroxide. Since the majority of biological membranes translocate Ca or other alkali metal ions, the opportunity for interaction with superoxide within the membrane may be considerable (Ca and calmodulin are required for superoxide production by leukocytes ). Under pathological circumstances calcium peroxide could be formed and lipid peroxidation initiated. The breakdown of membrane capacitance as a consequence of this may be deleterious in a number of ways. For example, the loss of a critical electric field may remove the driving force for energy-dependent processes associated with charge transfer. On the other hand, circumstances may be established which bring about unrestrained and unmodulated metabolic activity, as in cancer. 

the electrochemical interpretation of metabolism adopted here allows not only a new approach to an understanding of metabolic regulation, but also provides possible insights into the mechanism of many diseases. 

MICHAEL N. BERRY, ANTHONY R. GRIVELL, and PATRICIA 6. WALLACE 

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