Effects of non-metabolizable analogs on the distribution of amino acids in the rat

Abstract

The injection into the normal or adrenalectomized rat of [alpha]-aminoisobutyric acid caused the loss from the liver within 2 h of 1/3 to 2/3 of its normal content of the various neutral amino acids. At the same time a profound aminoaciduria was produced, including the cationic as well as the neutral amino acids. Indeed, the early effect on lysine excretion was exceptionally strong, although that on cystine later became even stronger. The N-methyl derivative of [alpha]-aminoisobutyric acid produced an aminoaciduria limited to proline and hydroxyproline, but the action on the retention of neutral amino acids by the liver was still general. Two other analogs, [alpha],[alpha] diethylglycine and [alpha],[alpha]-dicyclopropylglycine, structurally designed to minimize their reactivity with known transport systems, showed weak and negligible effects, respectively, on both the hepatic retention and the renal excretion of amino acids. These associations, together with the metabolic inertness of the test substances, indicate that the above effects arise from competition for transport. Inclusion of [alpha]-aminoisobutyric acid in the diets of young rats inhibited their growth in approximate correspondence to the decrease in food intake.