STUDIES ON MECHANISMS OF TRYPTOPHAN PYRROLASE INHIBITION DURING ENDOTOXIN POISONING
Rept. for 1 Dec 1964-28 Feb 1965
BRYN MAWR COLL PA DEPT OF BIOLOGY
Pagination or Media Count:
The inhibition of tryptophan pyrrolase in vitro by plasma and certain other native substances was investigated in an attempt to elucidate mechanisms responsible for the assumed decrease in activity of this enzyme in vivo during endotoxin poisoning. The inhibitor in plasma was present in normal mice, but increased significantly in endotoxin-poisoned, cortisone-protected, tolerant and challenged tolerant mice. On the basis of its physical properties and kinetics of inhibition, the plasma inhibitor was identified circumstantially as a globin. Results of kinetic studies eliminated the plasma inhibitor as a causal factor in the irreversible decrease in activity of tryptophan pyrrolase in whole homogenates of liver from endotoxin-poisoned mice. The enzyme was also found to be inhibited by citrate, the concentration of which increases substantially in the liver during endotoxicosis. Since inhibition by citrate could not be reversed by excess cofactor or substrate, it was concluded that at least part of the decreased activity of tryptophan pyrrolase in whole homogenates of poisoned mice was the result of inhibition by citrate.