Directed Alteration of Renal Coproporphyrinogen Metabolism

Mercury-Directed Alteration of Renal Coproporphyrinogen Metabolism 

The mechanism underlying the accumulation of 5- and 4-carboxyl porphyrins observed during mercury exposure has been shown to involve mercuric ion (Hg ) (or CH3Hg )-directed impairment of renal coprogen metabolism (Woods and Southern 1989). Coprogen oxidase from kidney is highly sensitive to inhibition by Hg in vitro and in vivo. Woods and Southern (1989) assessed the effects of Hg at various concentrations on coprogen oxidase in mitochondrial preparations from rat liver and kidney in vitro. The activity of the enzyme from both tissues was inhibited in a dose-related manner, with activity reduced to approximately 50% of control levels by Hg at 100//M in reaction mixtures. 

In studies in vivo (Woods and Fowler 1977 Woods and Southern 1989), treatment of male Sprague Dawley rats with methyl mercury hydroxide (MMH) for 6 weeks at 0.6 or 1.2mg/kg per day by drinking water produced a pronounced coproporphyrinuria characterized by a dose-related increase in the urinary coproporphyrin concentration up to 20 times control levels. Renal coprogen oxidase activity was depressed by as much as 56% of the control value 3 weeks after initiation of MMH treatment, whereas hepatic coprogen oxidase was not affected. Depression of renal coprogen oxidase activity correlated closely with increasing mercury levels in the kidney, suggesting that the interaction of Hg either with the enzyme itself 

Of additional interest with regard to the porphyrinogenic action of mercury is the observation from animal studies that prolonged mercury exposure is characterized by the excretion in the urine of an atypical porphyrin, not normally found in urine of unexposed subjects, which elutes on HPLC approximately mid-way between the 5- and 4-carboxyl porphyrins (Woods et al. 1991). This porphyrin has been referred to as precopro-porphyrin in several previous publications (Bowers et al. 1992 Woods et al. 1993) and appears to be unique to mercury exposure. Absorption and electrospray ionizing mass spectroscopic analyses have suggested that this atypical porphyrin shares structural properties of a keto derivative of isocoproporphyrin. However, the precise structural characteristics as well as the biochemical etiology of this porphyrin remain to be established. This porphyrin has been detected in urine both of mercury-exposed animals and human subjects (Woods et al. 1991, 1993). 

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