Cytochrome P450 research and The Journal of Biological Chemistry

Abstract

In honor of the 100th birthday of Dr. Herbert Tabor, JBC's Editor-in-Chief for 40 years, I will review here JBC's extensive coverage of the field of cytochrome P450 (P450) research. Research on the reactions catalyzed by these enzymes was published in JBC before it was even realized that they were P450s, i.e. they have a "pigment" with an absorption maximum at 450 nm. After the P450 pigment discovery, reported in JBC in 1962, the journal proceeded to publish the methods for measuring P450 activities and many seminal findings. Since then, the P450 field has grown extensively, with significant progress in characterizing these enzymes, including structural features, catalytic mechanisms, regulation, and many other aspects of P450 biochemistry. JBC has been the most influential journal in the P450 field. As with many other research areas, Dr. Tabor deserves a great deal of the credit for significantly advancing this burgeoning and important topic of research.

Keywords: cytochrome P450; eicosanoid; endoplasmic reticulum (ER); mitochondria; retinoid; steroid.

Figure 1.

Roles of P450s in the bioactivation and detoxication of chemicals: The complex example of phenacetin. Acetaminophen (paracetamol, Tylenol®) is widely used as an analgesic, safe at low doses and hepatotoxic at high levels (15). Phenacetin has been classified as a carcinogen and withdrawn from use. Only in a few cases are the structures of the protein and DNA adducts known. Some of the indicated P450s have been identified in different species, including humans (14, 15).

Figure 2.

P450s involved in steroid metabolism. The pathways are dominated by P450s, with the only other major players being dehydrogenases.

Figure 3.

Oxidations of arachidonic acid catalyzed by P450s (67–72). The four epoxides (epoxytrienoic acids or EETs) are formed primarily by P450 Family 2C and 2J enzymes, and the ω-hydroxylation product (20-hydroxyeicosatetrenoic acid or 20-HETE) is formed primarily by human Family 4A and 4F enzymes. The epoxides have roles as vasodilators. 20-Hydroxyeicosatetrenoic acid can exert both pro-hypertensive (vasoconstriction) and anti-hypertensive (natriuresis) effects, depending on its site of synthesis.

Figure 4.

Dr. Herbert Tabor (left) and the author at lunch at Dr. Tabor's home in 2016.