-Methyl Protoporphyrin IX: An Understudied Porphyrin

Overview

Journal Chem Res Toxicol

Publisher American Chemical Society

Specialty Toxicology

Date 2022 Dec 2

PMID 36459538

Authors

Lauren Xu

Qian Qi

Junjie Zhu

Xiaochao Ma

Affiliations

Soon will be listed here.

Abstract

-Methyl protoporphyrin IX (NmePPIX) is a derivative of protoporphyrin IX (PPIX) and the lattice of heme. Certain xenobiotics strongly induce NmePPIX production in the liver. The existence of endogenous NmePPIX in untreated animal liver has also been reported. The detailed mechanisms of NmePPIX biosynthesis remain unclear, but cytochrome P450 enzymes are thought to be critical in xenobiotic-induced NmePPIX production. High levels of NmePPIX cause PPIX accumulation because NmePPIX is a potent inhibitor ( = 7 nM) of ferrochelatase, the last enzyme in the heme biosynthesis pathway that converts PPIX to heme. NmePPIX is also involved in several other physiological processes, including inhibition of nitric oxide production and promotion of lamin aggregation. Compared to the two well-characterized porphyrins, PPIX and heme, NmePPIX is understudied regarding the mechanism of formation, fate, and physiological functions. This Review summarizes the current understanding of NmePPIX and provides perspectives on areas of future research on NmePPIX.

Citing Articles

Roles of the ABCG2 Transporter in Protoporphyrin IX Distribution and Toxicity.

Qi Q, Gu R, Zhu J, Anderson K, Ma X Drug Metab Dispos. 2024; 52(11):1201-1207.

PMID: 38351044 PMC: 11495668. DOI: 10.1124/dmd.123.001582.

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