Understanding Coproporphyrins and Their Disposition: Coproporphyrinuria is Common, of Diverse Cause, and Rarely Indicates Porphyria.

Coproporphyrins (CPs) are often mildly increased in plasma and urine, which leads to erroneous overdiagnosis of porphyrias. Herein we provide an overview of normal CP metabolism and factors that influence its disposition. We reviewed extant literature and here summarize and put into context current knowledge of CP metabolism and its disposition. CPs are formed as byproducts of normal heme synthesis. Normally they are removed chiefly by hepatocytes into bile and then stool. Organic anion-transporting peptides (OATPs) and multidrug resistance-associated proteins facilitate the uptake of CPs into epithelial cells and removal. Xenobiotics inhibit the activities of multidrug resistance-associated proteins and/or OATPs and affect the metabolism and disposition of CPs. CP concentrations are used as endogenous probes for assessing altered functions of OATPs. Diverse liver diseases and disorders lead to decreased secretion of CPs into bile and thus to increased concentrations of CPs in plasma and urine. Usually, mild to moderate increases in urinary CPs are due to alcohol, heavy metals, drug effects on transporters, or nonporphyric liver diseases not to porphyrias or to other inherited syndromes.