Urinary porphyrins are oxidized intermediate metabolites of heme biosynthesis and are readily excreted in excess when porphyrinogens accumulate as a result of inhibition of specific enzymes in the heme biosynthetic pathway. Heme is required for oxygen binding, transport and utilization, cytochromes, and electron transport in mitrochondira. The high rate of production of heme facilitates the use of urinary porphyrins as early and sensitive biomarkers of disorders in heme production, and has long been associated with genetic disorders, metabolic disturbances/diseases, nutritional status, oxidative stress, and high level exposure to toxic chemicals or metals.
Specific urinary porphyrin profiles have been associated with very high levels of toxic metals such as mercury (Hg), lead and arsenic. Mercury specifically inhibits two enzymes in porphyrinogen metabolism: uroporphyrinogen decarboxylase and coproporphyrinogen oxidase (CPOX). Inhibition of those two enzymes, particularly in the renal cortex, results in accumulation of pentacarboxyporphyrinogen and coproporphyrinogen III. Oxidation of the abnormally elevated porphyrinogens results in elevated urinary levels of total porphyrins, pentacarboxyporphyrin and coproporphyrin III. Recent research has identified an additional abnormal porphyrin in the urine of Hg-exposed dentists and also in rats fed very high levels of mercury for extended periods of time. A third Hg-associated porphyrin is most commonly referred to as “precoproporphyrin” as it elutes after pentacarboxyporphyrin and before coproporphyrin I. The recently described precoproporphyrin has yet to be characterized with respect to molecular identity and appears to be elevated in Hg exposed individuals who carry a variant of the CPOX gene (CPOX4 polymorphism). Research at Doctor’s Data, Inc. has identified three separate precoproporphyrin peaks. Since knowledge about the Hg-associated precoproporphyrin entities is limited, we report the levels of all three peaks separately, as well as the total, for research use. Since uroporphyrin levels are not known to be affected by Hg, we also report the total precoproporphyrins-to-uroporphyrin ratio to increase the sensitivity for detecting abnormalities in individuals with low heme biosynthesis as may occur in children with nutritional deficiencies and/or autism.
Arsenic exposure has been associated with elevated levels of uroporphyrins and coproporphyrin I, and an elevated ratio of coproporphyrins (I: III). Lead exposure has been associated with elevated levels of coproporphyrin III.
Exposure to hexachlorobenzene and dioxin has been associated with elevated levels of uroporphyrins. Exposure to polyvinylchloride (PVC) and polybrominated biphenyl has been associated with elevated levels of coproporphyrins.
Various drugs and other substances can suppress enzymes involved in porphyrin metabolism and affect the levels of urinary porphyrins. Such compounds include alcohol, sedatives, analgesics, antibiotics, estrogens, and oral contraceptives. Anemia, pregnancy, and liver disease can also affect porphyrin metabolism.
The Urine Porphyrins test is best used in conjunction with urine toxic metals pre- and post-provocation testing.