Decarboxylation of alpha-ketoisovaleric acid after oral administration in man.

The keto analogues of essential amino acids represent a promising therapeutic modality in hereditary and acquired disorders of nitrogen metabolism. The utilization of these substances in humans has been assayed primarily by nitrogen balance studies. A simple and accurate breath excretion test for 14CO2 enabled us to measure the decarboxylation of 1-14C-alpha-ketoisovaleric acid (KIV, the keto analogue of valine) in two normal and six diseased subjects. Normal volunteers as well as patients with gastrectomy, hepatic failure, renal failure, and myotonic dystrophy were tested in 5-g protein diets supplemented with essential amino acids and KIV (in place of valine). The normal volunteers and the gastrectomy patient were then restudied on 120 g protein/day. With low protein intake, 13 to 32% of ingeted KIV underwent rapid decarboxylation, and this proportion appeared to correlate inversely with damage to organ systems containing the branched-chain keto acid dehydrogenase. With high protein intake, the proportion decarboxylated rose to 44 to 53%. Thse results confirm that the decarboxylation of KIV in man varies under different conditions of dietary intake and metabolic disease. The 14CO2 brewth excretion test is applicable to other related analyses of carboxylic acid metabolism in human subjects.