alpha-Keto and alpha-hydroxy branched-chain acid interrelationships in normal humans

• Published in: The Journal of nutrition Vol. 123; no. 9; pp. 1513 - 1521
• Main Authors: Hoffer, L.J, Taveroff, A, Robitaille, L, Mamer, O.A, Reimer, M.L.J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutritional Sciences 01.09.1993; American Institute of Nutrition
• Subjects: ACIDE AMINE; Adult; ADULTE; ADULTOS; Amino acids; Amino Acids, Branched-Chain - blood; Amino Acids, Branched-Chain - pharmacokinetics; AMINOACIDOS; Biological and medical sciences; CETOACIDE; CETOACIDOS; Diet; DIETA; Dietary Proteins - administration & dosage; Dietary Proteins - pharmacology; Evaluation Studies as Topic; Fasting - blood; Fasting - metabolism; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Humans; Isoleucine - blood; Isoleucine - pharmacokinetics; Keto Acids - blood; Leucine - blood; Leucine - pharmacokinetics; Male; Mass Spectrometry; METABOLISME; METABOLISMO; Nutrition; Oxidation-Reduction; PLASMA SANGUIN; PLASMA SANGUINEO; Protein Binding; PROTEINAS; PROTEINE; REGIME ALIMENTAIRE; Time Factors; Valerates - blood; Valine - blood; Valine - pharmacokinetics; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Human; Proteins; Branched chain; Fasting; Nutrition; Diet; Aminoacid; Ketoacid; Metabolism; Feeding; Quantitative analysis; Blood plasma
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/123.9.1513

Plasma concentrations of the branched-chain amino acids leucine, isoleucine and valine, and those of leucine's and isoleucine's transamination products alpha-ketoisocaproic acid (KICA) and alpha-keto-beta-methylvaleric acid (KMVA), respectively, are known to increase after a protein 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 whether 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-hydroxyisocaproic acid (HICA), alpha-hydroxy-beta-methylvaleric acid (HMVA) and alpha-hydroxyisovaleric acid (HIVA)], in normal volunteers immediately after a protein meal or during a 60-h fast. We also determined the oxidoreduction equilibrium constants for HIVA/KIVA and HICA/KICA and their extent of plasma protein binding. in subjects in the postabsorptive state, 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. Shortly after a protein meal, KICA and KMVA concentrations increased significantly 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 metabolites increased gradually. The high plasma keto/hydroxy acid ratios were not related to their Keg, which favored alpha-hydroxy analogue formation. The reduction of the branched-chain alpha-keto acids to their alpha-hydroxy analogues seems to take place too slowly to attain thermodynamic 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 isol