Research Activities
In his research, he initially specialized in amino acid metabolism, including the utilization of D-amino acids and non specific forms of nitrogen. He then studied the relationship between protein and vitamin A which led to the finding that the amount, as well as biological value, of dietary protein are important in the process of converting carotene to vitamin A. Other studies dealt with metabolic changes during cachexia of tumor-bearing animals. One of the most striking affects of tumor on the host was the depression of enzyme catalase in the livers and in the kidneys which some investigators thought was due to a hypothetical substance, referred to as toxohormone. This was disproved by finding significant levels of the enzyme in liver tumors.
A number of his studies dealt with the question of enzyme turnover in vivo. Using specific metabolic inhibitors, he evaluated relative rates of synthesis and degradation of the enzyme catalase under a variety of physiological, pathological and pharmacological conditions. These studies led to the conclusion that the rate of synthesis rather than the rate of destruction may be the preferential way of the mammalian organism to control its enzyme levels.
His finding of greatly different levels of catalase activity in certain substrains of mice, which were under genetic control, provided an excellent model for pursuing fundamental research in biochemical genetics in the mammalian system. The analyses of the first, the second the backcross generations between high-enzyme and low-enzyme mouse substrains showed that the difference was due to a single autosomal gene pair with low dominant to high. Using specific metabolic inhibitors, it was subsequently found that the genetic difference between the two substrains lies primarily in the markedly increased rate of the enzyme destruction in the liver of one of the substrains. This was a unique finding since in all normal rats and mice studied previously the rates of enzyme destruction seemed to be almost constant. Although transient alteration in the rate of enzyme degradation has been observed under certain physiological conditions with other enzyme systems, the observation on catalase iwas believed to be the first demonstration of such regulatory mechanism under genetic control.
Other studies dealt with the morphology, biochemistry and physiology of microbodies, on which he collaborated with Prof. Z.. Hruban of the University of Chicago, that led to the monograph Microbodies and Related Particles (1969).
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