Moonlighting in drug metabolism

Abstract

Drug metabolizing enzymes catalyze the biotransformation of many of drugs and chemicals. The drug metabolizing enzymes are distributed among several evolutionary families and catalyze a range of detoxication reactions, including oxidation/reduction, conjugative, and hydrolytic reactions that serve to detoxify potentially toxic compounds. This detoxication function requires that drug metabolizing enzymes exhibit substrate promiscuity. In addition to their catalytic functions, many drug metabolizing enzymes possess functions unrelated to or in addition to catalysis. Such proteins are termed ‘moonlighting proteins’ and are defined as proteins with multiple biochemical or biophysical functions that reside in a single protein. This review discusses the diverse moonlighting functions of drug metabolizing enzymes and the roles they play in physiological functions relating to reproduction, vision, cell signaling, cancer, and transport. Further research will likely reveal new examples of moonlighting functions of drug metabolizing enzymes.

Keywords:

• Moonlighting
• drug metabolizing enzymes
• aldehyde dehydrogenase
• crystallins
• aminopeptidase N
• dicarbonyl/xylulose reductase
• glutathione peroxidase
• glutathione transferases
• arylamine N-acetyltransferase
• quinone oxidoreductase

Acknowledgment

The authors thank Emeritus Professor Angela Dulhunty for her constructive advice on the GST/Ryanodine Receptor interactions and Professor Patrick E. Hanna for helpful and insightful discussions.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Project Grants APP1124673 and APP1156455 to Philip Board from the National Health and Medical Research Council of Australia (NHMRC).