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J Pharmacol Exp Ther. 2016 Feb;356(2):267-75. doi: 10.1124/jpet.115.228130. Epub 2015 Nov 20.

Protoporphyrin IX: the Good, the Bad, and the Ugly.

Author information

1
Department of Pharmaceutical Sciences, Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (M.S., X.M.); and Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas (K.E.A.).
2
Department of Pharmaceutical Sciences, Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (M.S., X.M.); and Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas (K.E.A.) mxiaocha@pitt.edu.

Abstract

Protoporphyrin IX (PPIX) is ubiquitously present in all living cells in small amounts as a precursor of heme. PPIX has some biologic functions of its own, and PPIX-based strategies have been used for cancer diagnosis and treatment (the good). PPIX serves as the substrate for ferrochelatase, the final enzyme in heme biosynthesis, and its homeostasis is tightly regulated during heme synthesis. Accumulation of PPIX in human porphyrias can cause skin photosensitivity, biliary stones, hepatobiliary damage, and even liver failure (the bad and the ugly). In this work, we review the mechanisms that are associated with the broad aspects of PPIX. Because PPIX is a hydrophobic molecule, its disposition is by hepatic rather than renal excretion. Large amounts of PPIX are toxic to the liver and can cause cholestatic liver injury. Application of PPIX in cancer diagnosis and treatment is based on its photodynamic effects.

PMID:
26588930
PMCID:
PMC4727154
DOI:
10.1124/jpet.115.228130
[Indexed for MEDLINE]
Free PMC Article

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