ALPHA-KETO AND ALPHA-HYDROXY BRANCHED-CHAIN ACID INTERRELATIONSHIPS IN NORMAL HUMANS

Plasma concentrations of the branched-chain amino acids leucine, isole ucine and valine, and those of leucine's and isoleucine's transaminati on products alpha-ketoisocaproic acid (KICA) and alpha-keto-beta-methy lvaleric acid (KMVA), respectively, are known to increase after a prot ein meal or during extended fasting, but little or no increase in the concentration of valine's transamination product, alpha-ketoisovaleric acid (KIVA), has been observed under these conditions. To determine w hether this could be explained by the conversion of KIVA to its alpha- hydroxy analogue, we measured the plasma concentrations of KICA, KMVA and KIVA, as well as their alpha-hydroxy analogues [alpha-hydroxyisoca proic acid (HICA), alpha-hydroxy-beta-methylvaleric acid (HMVA) and al pha-hydroxyisovaleric acid (HIVA)], in normal volunteers immediately a fter a protein meal or during a 60-h fast. We also determined the oxid oreduction equilibrium constants for HIVA/KIVA and HICA/KICA and their extent of plasma protein binding. In subjects in the postabsorptive s tate, the plasma concentrations of KICA and KMVA were 100 times those of HICA and HMVA, whereas that of KIVA was only twice that of HIVA. Sh ortly after a protein meal, KICA and KMVA concentrations increased sig nificantly by 30 and 60%, respectively, whereas that of KIVA decreased by 25% (P < 0.05). HICA, HMVA and HIVA concentrations did not change. During prolonged fasting the plasma concentrations of all six metabol ites increased gradually. The high plasma keto/hydroxy acid ratios wer e not related to their K(eq) which favored alpha-hydroxy analogue form ation. The reduction of the branched-chain alpha-keto acids to their a lpha-hydroxy analogues seems to take place too slowly to attain thermo dynamic equilibrium. The acute decrease in plasma KIVA after a protein meal may be due to a lower rate of valine intracellular transport or transamination in the presence of increased plasma leucine and isoleuc ine concentrations.