57 varieties: the human cytochromes P450

Area of Science:

• Biochemistry
• Pharmacology
• Enzymology

Background:

• The human cytochrome P450 (CYP) superfamily comprises heme-thiolate enzymes.
• These enzymes play critical roles in both endogenous metabolic pathways and the biotransformation of xenobiotics.
• Understanding CYP functionality is vital for drug development and toxicology.

Purpose of the Study:

• To review the known human cytochrome P450 enzymes.
• To delineate the functional roles of these enzymes, distinguishing between xenobiotic and endogenous metabolism.
• To focus on the involvement of CYP1, CYP2, and CYP3 families in Phase I foreign compound metabolism.

Main Methods:

• Comprehensive literature review of characterized human P450 enzymes.
• Analysis of reported metabolic functions, including drug metabolism and endogenous compound biotransformation.
• Categorization of enzymes based on their primary metabolic roles and involvement in specific phase I pathways.

Main Results:

• Approximately half of the 57 characterized human P450s are involved in drug and xenobiotic metabolism.
• The other half of human P450s are essential for endogenous metabolic processes, including steroid, prostanoid, eicosanoid, and fatty acid metabolism.
• The CYP1, CYP2, and CYP3 families are highlighted for their significant roles in Phase I xenobiotic metabolism.

Conclusions:

• Human cytochrome P450 enzymes exhibit diverse functional roles, essential for both detoxification and endogenous biosynthesis.
• The CYP1, CYP2, and CYP3 families are key players in the initial steps of foreign compound metabolism.
• This review provides a foundational overview of human CYP enzyme functionality, relevant for pharmacological and toxicological research.