Lj. Hoffer et al., ALPHA-KETO AND ALPHA-HYDROXY BRANCHED-CHAIN ACID INTERRELATIONSHIPS IN NORMAL HUMANS, The Journal of nutrition, 123(9), 1993, pp. 1513-1521
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.