Studies with experimental animal models have led the way
to an understanding of the P450 enzymes, and much of the
information about these models has been applicable to the
human orthologs. However, with the acquisition of
knowledge about the experimental animal systems came the
realization that many aspects could be understood only by
studying humans. Over the years, biochemical measurements
had been made on human liver surgical samples (for
review see ref 5). Much of this information involved levels of
P450, cytochrome b5, and NADPH-cytochrome c reduction
rates plus rates of some typical P450-dependent catalytic activities.
Kaschnitz and Coon (6) were able to fractionate human
liver microsomes into three components enriched in
P450, NADPH-P450 reductase, and phospholipid, and
demonstrate catalytic activities when these fractions were
recombined. At about this time Conney (2) and associates
carried out in vivo studies involving enzyme induction which
have formed the basis for some of our current understanding
of human P450 function.