MICROSOMES AND DRUG OXIDATIONS: PERSPECTIVES AND CHALLENGES

Abstract

This chapter discusses the cytochrome P-450s that are present in mammals and in many other forms of life such as bacteria, fungi, insects, and plants. The widespread occurrence of the cytochrome P-450s in nature provides opportunities for research on similarities and differences in these hemoproteins in different life forms. It also provides the opportunities for exploring the reasons for the presence of the multiple forms of cytochrome P-450 in nature, and for tracing the origin and evolution of this versatile and important group of enzymes. There is a need to determine how many cytochrome P-450s exist in experimental animals and in man, and to determine the function of each hemoprotein. Better methods are needed for the separation and purification of multiple cytochrome P-450s. The use of specific antibodies to prepare immunoaffinity columns is an approach to this problem. Monospecific antibodies are being used for quantifying the concentration of specific forms of the cytochrome P-450s in liver. The general use of monospecific antibodies for quantifying the concentrations of specific forms of cytochrome P-450 in various tissues should expand. Studies with whole liver homogenate, microsomes, and with purified cytochrome P-450s from human beings may allow to evaluate pathways of metabolism of experimental drugs and environmental pollutants in man.