We have discussed six different types of mechanisms that are used to adapt enzyme function to allow metabolism to respond to changing physiological demands or environmental stresses. Although the present discussion has been largely limited to enzymes of glycolysis, the principles are equally applicable to virtually all aspects of metabolic function. In particular, control via reversible protein phosphorylation is proving to be widespread for the coordination of diverse cellular enzymes and proteins (Boyer and Krebs, 1987). For example, reversible phosphorylation is now well known to extend to the control of membrane ion-channel proteins, regulating both their incorporation into membranes and their activity once inserted (Reuter, 1987). Such coordinated control over a wide variety of cellular processes is proving to be critical to metabolic rate depression. Hibernating mammals, for example, retain control over membrane potential difference as body temperature falls to ambient; the same species in the summer-adapted state, however, are just as susceptible to the destructive effects of hypothermia on membrane ion regulation as are humans. The lessons to be learned from comparative biochemistry are many. The combinations of metabolic controls that can be applied for the adaptation of enzyme function are nearly limitless and mechanisms can be found to overcome almost any environmental constraint or meet any physiological demand. Increasingly, we are applying the information gained from comparative studies and nowhere is this more true that in the development of organ preservation technology. Both the mechanisms of metabolic rate depression and of freeze tolerance that are found in animals are directly applicable to the development of mechanisms for organ transplant technology and some of the most effective therapies presently used (e.g., glycerol as a cryoprotectant; inhibitors of membrane ion transport to reduce energy demands) effectively mimic the strategies used in the natural situation. © 1995 Elsevier B.V.
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