Inhibition of gluconeogenesis in isolated rat kidney tubules by branched chain alpha-ketoacids.

Isolated rat kidney tubules served as a model to investigate the direct effects of branched chain aminoacids, their alpha-ketoderivatives, and of the homolog straight chain aliphatic alpha-ketoacids on renal gluconeogenesis. It is demonstrated that the alpha-ketoderivatives, rather than the branched chain aminoacids themselves, are potent inhibitors of renal gluconeogenesis from precursors, entering the glucogenic pathway on all levels below and above triose phosphate. This inhibitory action is not specific for the branched chain alpha-ketoacids, since it is also observed in the presence of the homolog straight chain aliphatic alpha-ketoacids. The suppression of renal gluconeogenesis by alpha-ketoacids can not be explained by a direct inhibition of gluconeogenic reactions, by inhibition of cellular respiration, or by interference with the stimulatory action of Ca++, cAMP, and L-lysine on renal gluconeogenesis. Although the point of inhibitory attack of alpha-ketoacids in renal gluconeogenesis could not be localized, an impairment of the kidney to respond to metabolic acidosis with an increase of gluconeogenesis was observed, since the pH optimum of renal gluconeogenesis was shifted from pH 6.8 to pH 7.7 in the presence of alpha-ketoisovaleric acid.