Redox regulation of cysteine-dependent enzymes.
It is well-established that maintenance of the intracellular redox (i.e., reduction-oxidation) state is critical for cell survival and that prolonged or abnormal perturbations toward oxidation result in cell dysfunction. This is exemplified by the widespread observation of oxidative stress in many pathological conditions, as well as the positive effects of antioxidants in treating certain conditions or extending the life span itself. In addition to the effects of oxidation on the lipid bilayer and modification of DNA in the nucleus, proteins are also modulated by the redox state. One of the primary targets of oxidation within a protein is the AA cysteine, whose thiol side chain is highly sensitive to all types of oxidizing agents. Although this sensitivity is used to prevent oxidation within the cell by potent defense mechanisms, such as glutathione, the use of cysteine in the active site of enzymes leaves them open to oxidant-mediated damage. Whether the damage is due to a pathological condition or to postmortem mediated loss of redox homeostasis, cysteine-dependent enzymes are targets of all forms of reactive oxygen, nitrogen, and sulfur species. A greater understanding of the redox-mediated control of cysteine-dependent enzymes opens the door to the selective use of antioxidants to prevent or reverse the cellular damage their inhibition causes.
Guttmann
R P
RP
Department of Gerontology, and the Sanders-Brown Center on Aging, University of Kentucky, Lexington, USA. rodneyg@uky.edu
D000375:Aging / Q000378:metabolism / Q000502:physiology; D000824:Animal Nutritional Physiological Phenomena / Q000502:physiology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000502:physiology; D002468:Cell Physiological Phenomena / Q000502:physiology*; D002477:Cells / Q000201:enzymology* / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism* / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
D000975:Antioxidants; D017382:Reactive Oxygen Species; D003545:Cysteine