Genetic and Enzymatic Characteristics of CYP2A13 in Relation to Lung Damage.

Radim Vrzal

doi:10.3390/ijms222212306

Abstract

Cytochrome P450 2A13 is an omitted brother of CYP2A6 that has an important role in the drug metabolism of liver. Due to extrahepatic expression, it has gained less attention than CYP2A6, despite the fact that it plays a significant role in toxicant-induced pulmonary lesions and, therefore, lung cancer. The purpose of this mini-review is to summarize the basic knowledge about this enzyme in relation to the substrates, inhibitors, genetic polymorphisms, and transcriptional regulation that are known so far (September 2021).

Highlights

Xenobiotic-metabolizing enzymes (XMEs) play a crucial role in the detoxification of foreign compounds
They are bound to the membrane of the endoplasmic reticulum with the C-terminus and using NADPH generated by cytochrome P450 reductase (CYPOR; 1.6.2.4)
Since this compound was labeled as a carcinogen by the International Agency for Research on Cancer (IARC) in 2012, it is inseparably connected with CYP2A13

Summary

Introduction

Xenobiotic-metabolizing enzymes (XMEs) play a crucial role in the detoxification of foreign compounds. The most abundant subgroup is the cytochrome P450 superfamily (CYP; 1.14.X.X), a heme that contains enzymes that participate in phase I of biotransformation They are bound to the membrane of the endoplasmic reticulum with the C-terminus and using NADPH generated by cytochrome P450 reductase (CYPOR; 1.6.2.4). Each individual member within the subfamily is further marked with a number (e.g., CYP2A6, CYP2A13) These are located on the same chromosome, and it is believed that they were created throughout the evolution by gene duplication of the whole CYP superfamily [1–3]). One of the key components of cigarette smoke is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobaccospecific nitrosamine ketone, the metabolism of which is mediated by CYP2A13 Since this compound was labeled as a carcinogen by the International Agency for Research on Cancer (IARC) in 2012, it is inseparably connected with CYP2A13. Due to CYP2A13 being less investigated than CYP2A6 (approximately 10 times fewer hits at PUBMED in September 2021), the significant role in the biotransformation of tobacco carcinogens, and possibly the key role in the pathology of tobacco-induced lung cancer, this mini-review summarizes basic knowledge about CYP2A13

Tissue Distribution

Substrates and Inhibitors

Skatole

Genetic Polymorphisms

Findings

Conclusions