Porphyrin Metabolism as Indicator of Metal Exposure and Toxicity

Abstract

Numerous studies during the past several decades have demonstrated that porphyrins and other constituents of the heme biosynthetic pathway might serve as sensitive and specific biomarkers of toxic metal exposures in human subjects. Porphyrins (in the reduced form, porphyrinogens) are formed as intermediates of heme biosynthesis in essentially all eukaryotic tissues and are readily measured following extraction in the oxidized form (porphyrins) in blood cells, urine, feces, and other accessible tissues. The utility of porphyrins as biomarkers of metal exposures is based largely on the properties of metals to selectively alter porphyrinogen metabolism in target tissues by mechanisms which lead to metal-specific changes in urinary porphyrin excretion patterns. Of particular importance with respect to the utility of porphyrins as biomarkers of metal effects in target tissues is the property of some specific metals, not only to impair porphyrin(ogen) metabolism, but also to facilitate the oxidation of reduced porphyrins which subsequently accumulate in tissue cells. Evidence indicates that the pro-oxidant action of metals which promotes porphyrinogen oxidation may also underlie the oxidation of other cellular constituents, such as lipids and proteins, a postulated cause of cell injury. Hence, a common mechanistic etiology underlying the porphyrinogenic and tissue-damaging properties of metals provides the rationale for use of porphyrin measurements as an indicator of metal exposure as well as potential toxicity.