Evolution of bioinorganic motifs in P450-containing systems

Abstract

T h e choice of bioinorganic motifs by Nature results in a spectacular variety of active-site structures even within the same protein family. Here, we use the concept of the bioinorganic motif to discuss the function and evolution of P450containing and other related systems. Apart from P450, these systems include a FAD flavoprotein or domain, a F M N domain, ferredoxins and cytochrome b,. Analysis of available complete genomes can shed light on what an ancestral P450containing system could be.

Vascular biotransformation of organic nitrates is independent of cytochrome P450 monooxygenases

“…CYP enzymes are membrane-bound and haem-containing terminal monooxygenases (Fleming, 2001). They are part of a multienzyme system comprising a flavin adenine dinucleotide (FAD)/flavin mononucleotide (FMN)-containing NADPH-POR (gene name) (Degtyarenko & Kulikova, 2001;Fleming, 2001). POR is a key enzyme in transferring electrons to CYP enzymes, and, therefore, POR is essential for all functions performed by every CYP, including metabolism of lipids, hormone and cholesterol synthesis, and drug detoxification.…”

Emodin reverses CCl4 induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural changes: The in vivo evidence

“…It has been well established that the industrial solvent CCl 4 is an environmental hepatotoxicant 2,3 because CCl 3 ° and Cl° are formed as a result of its metabolic activation via cytochrome P450 (CYP), which in turn, initiates LPO. The CYPs constitute a large family of mono oxygenases capable of catalyzing an extraordinary range of biochemical reactions from the synthesis of cholesterol and bile acids to the metabolism of drugs, prodrugs and xenobiotics 4 . Aniline hydroxylase (AH) and amidopyrine‐N‐demethylase (AND) are microsomal drug metabolizing enzymes (MDMEs) of the CYP system, which are responsible for the metabolism of certain xenobiotics, especially CCl 4 .…”