Models of Superoxide Dismutases

Book · Wed May 20 04:00:00 EDT 1998

OSTI ID:770697

Cabelli, Diane E ^[1]; Riley, Dennis; Rodriguez, Jorge A; Valentine, Joan Selverstone; Zhu, Haining

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1. Brookhaven National Laboratory

In this review we have focused much of our discussion on the mechanistic details of how the native enzymes function and how mechanistic developments/insights with synthetic small molecule complexes possessing SOD activity have influenced our understanding of the electron transfer processes involved with the natural enzymes. A few overriding themes have emerged. Clearly, the SOD enzymes operate at near diffusion controlled rates and to achieve such catalytic turnover activity, several important physical principles must be operative. Such fast electron transfer processes requires a role for protons; i.e., proton-coupled electron transfer (''H-atom transfer'') solves the dilemma of charge separation developing in the transition state for the electron transfer step. Additionally, outer-sphere electron transfer is likely a most important pathway for manganese and iron dismutases. This situation arises because the ligand exchange rates on these two ions in water never exceed {approx}10{sup +7} s{sup -1}; consequently, 10{sup +9} catalytic rates require more subtle mechanistic insights. In contrast, copper complexes can achieve diffusion controlled (>10{sup +9}) exchange rates in water; thus inner-sphere electron transfer processes are more likely to be operative in the Cu/Zn enzymes. Recent studies have continued to expand our understanding of the mechanism of action of this most important class of redox active enzymes, the superoxide dismutases, which have been critical in the successful adaptation of life on this planet to an oxygen-based metabolism. The design of SOD mimic drugs, synthetic models compounds that incorporate this superoxide dismutase catalytic activity and are capable of functioning in vivo, offers clear potential benefits in the control of diseases, ranging from the control of neurodegenerative conditions, such as Parkinson's or Alzheimer's disease, to cancer.

• Research Organization: Brookhaven National Lab., Upton, NY (US)
• Sponsoring Organization: USDOE Office of Energy Research (ER) (US)
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 770697
• Report Number(s): BNL-65540
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS
COPPER COMPLEXES
DIFFUSION
DISEASES
ELECTRON TRANSFER
ENZYMES
FOREIGN EXCHANGE RATE
IN VIVO
ION EXCHANGE
IRON
LIGANDS
MANGANESE
METABOLISM
NEOPLASMS
PROTONS
SUPEROXIDE DISMUTASE