Regulation of isocitrate metabolism in peroxisomes in Tetrahymena pyriformis

Isocitrate dehydrogenase (NADP⁺-dependent) and isocitrate lyase compete for substrate in peroxisomes (microbodies) in the ciliated protozoan Tetrahymena pyriformis. Thus, some of the factors that might regulate the metabolism of isocitrate in Tetrahymena peroxisomes were studied. The dehydrogenase has a much greater affinity for isocitrate than does the lyase, but is subject to a concerted feedback inhibition by oxalacetate and glyoxylate. Concentrations of 25 μm of each cause almost complete inhibition. The degree of inhibition is greatly reduced unless NADP is present during a brief preincubation of the enzyme with the inhibitors. Either glyoxylate or oxalacetate alone is also capable of inhibiting the enzyme, although higher concentrations are required. In this case, there is no inhibition unless inhibitor and enzyme are preincubated in the presence of NADP. Neither the concerted inhibition nor that due to oxalacetate seems to be competitive with isocitrate. Properties of the enzyme from the soluble fraction of the cell were identical to those of the peroxisomal enzyme. Enzyme from mouse liver exhibited most of the properties observed with the Tetrahymena enzyme. The concerted inhibition of isocitrate dehydrogenase may be the means by which isocitrate in the peroxisome is shunted through the glyoxylate bypass.