Toxicological significance of enzyme

Friedman, M. (Editor). Nutritional and Toxicological Significance of Enzyme Inhibitors in Foods. Adv. Exp. Med. Biol. Plenum New York 1986 Vol. 199, 570 pages. 

A 32% increase in liver weights, along with a 187% increase in peroxisomal beta-oxidation activity, was noted in rats exposed to 1,000 mg/kg/day MIL-H-5606 for 26 days (Mattie et al. 1993). The toxicological significance of the changes in peroxisomal enzyme activities is unclear. 

Liver toxicity, as evidenced by alterations in the incorporation of lysine into liver proteins, was observed in rats administered 192 mg lead/kg/day by gavage as lead acetate for 9 weeks (Barratt et al. 1989). No effects were observed at 21 mg lead/kg/day. However, the toxicological significance of this finding is not known because neither serum enzymes nor histopathological evaluations were performed. 

Making useful predictions about metabolic reactions presents considerable difficulties. As a generalization it is not unreasonable to propose that all metabolic conversions of a molecule for which appropriate enzymes exist in the study animal will occur. The questions are which metabolites will predominate and what will be the toxicological significance of the metabolites. To add to the complications, there may be discontinuities in the relationship between quantities of metabolites and dose level if the enzyme responsible for the fastest metabolic conversion is present in fairly small amounts and becomes saturated, the product from a different enzyme may start to appear in large amounts. The need to be able to predict metabolism is nevertheless a... 

Masubuchi, Y., Horie, T. Toxicological significance of mechanism-based inactivation of cytochrome p450 enzymes by drugs. Crit. Rev. Toxicol. 2007, 37, 389-412. 

Intermediate-duration exposures of quail to methylmercury or Aroclor 1260 in the diet led to accumulation of porphyrins in liver hepatic porphyrin levels in quail exposed to both agents simultaneously were similar to levels predicted based on additivity of response (Leonzio 1996b). Combined exposure of rats or quail to commercial PCB mixtures and methylmercury appears to counteract PCB induction of hepatic CYP enzymes (Leonzio et al. 1996a Takabatake et al. 1980), but the toxicological significance of this interaction is unclear. 

Ohkawa, H., R. Ohkawa, I. Yamamoto, and J. E. Casida. 1972. Enzymic mechanisms and toxicological significance of hydrogen cyanide liberation from various organothiocyanates and organonitriles in mice and houseflies. Pestic. Biochem. Physiol. 2(1) 95-112. 

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