Summary
l-Alloisoleucine formation froml-isoleucine was studiedin vitro andin vivo. When a healthy subject was loaded withl-isoleucine, plasma levels ofl-isoleucine and 3-methyl-2-oxopentanoate (KMV), as well asl-alloisoleucine, increased. Peak values were reached successively and were in the orderl-isoleucine > > KMV > >l-alloisoleucine. Metabolic clearance ofl-isoleucine and KMV was rapid; clearance ofl-alloisoleucine was considerably delayed. When human skin fibroblast cultures were challenged withl-isoleucine, KMV accumulated at a gradually decreased rate, whereasl-alloisoleucine accumulated at a gradually accelerated rate. KMV andl-alloisoleucine formation were related and depended on thel-isoleucine concentration applied. In cell lines derived from MSUD patients (classical form), metabolite formation was only about 2-fold higher than in control strains. The relatively small difference between normal and MSUD fibroblastsin vitro as opposed to the striking differences between healthy subjects and MSUD patientsin vivo are discussed with respect to the significance of physiological mechanisms participating in the formation and degradation ofl-alloisoleucine in man.
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References
Batshaw, M. L., Brusilow, S. and Walser, M. Long-term management of a case of carbamyl phosphate synthetase deficiency using ketoanalogues and hydroxyanalogues of essential amino acids.Pediatrics 58 (1976) 227–235
Benson, J. V., Cormick, J. and Patterson, J. A. Accelerated chromatography of amino acids associated with phenylketonuria, leucinosis (maple syrup urine disease), and other inborn errors of metabolism.Anal. Biochem. 18 (1967) 481–492
Chen, T. R. In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoecht 33258 stain.Exp. Cell Res. 104 (1977) 255–262
Danner, D. J. and Priest, J. H. Branched-chain ketoacid dehydrogenase activity and growth of normal and mutant human fibroblasts: the effect of branched-chain amino acid concentration in culture medium.Biochem. Genet. 21 (1983) 895–905
Duggleby, R. G. A. A non-linear regression program for small computers.Anal. Biochem. 110 (1981) 9–18
Funk, M. A., Lowry, R. R. and Baker, D. H. Utilization of theL- andDL- isomers of α-keto-β-methylvaleric acid by rats and comparative efficacy of the keto analogs of branched-chain amino acids provided as ornithine, lysine and histidine salts.J. Nutr. 117 (1987) 1550–1555
Harper, A. E., Miller, R. H. and Block, K. P. Branched-chain amino acid metabolism.Annu. Rev. Nutr. 4 (1984) 409–454
Langenbeck, U., Wendel, U. and Luthe, H. Renal clearance of branched-chain 2-oxo acids in maple syrup urine disease.J. Clin. Chem. Clin. Biochem. 17 (1979) 176–177
Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J. Protein measurement with the Folin phenol reagent.J. Biol. Chem. 193 (1951) 265–275
Matthews, D. E., Ben-Galim, E., Haymond, M. W. and Bier, D. M. Alloisoleucine formation in maple syrup urine disease: isotopic evidence for the mechanism.Pediatr. Res. 14 (1980) 845–857
Meister, A. Studies ond- andl-α-keto-β-methylvaleric acid.J. Biol. Chem. 190 (1951) 269–276
Mitch, W. E., Walser, M. and Sapir, D. G. Nitrogen sparing induced by leucine compared with that induced by its keto analogue, α-ketoisocaproate, in fasting obese man.J. Clin. Invest. 67 (1981) 553–562
Schadewaldt, P. and Wendel, U. Functional differences in the catabolism of branched-chainl-amino acids in cultured normal and maple syrup urine disease fibroblasts.Biochem. Med. Metab. Biol. 41 (1989) 105–116
Schadewaldt, P., Beck, K. and Wendel, U. Analysis of maple syrup urine disease in cell culture: use of substrates.Clin. Chim. Acta 184 (1989a) 47–56
Schadewaldt, P., Hammen, H.-W. and Wendel, U. Kinetic characterization of human branched-chain amino acid aminotransferase activity.Biol. Chem. Hoppe-Seyler 370 (1989b) 951
Schadewaldt, P., Hummel, W., Trautvetter, U. and Wendel, U. A convenient enzymatic method for the determination of 4-methyl-2-oxopentanoate in plasma: comparison with high performance liquid chromatographic analysis.Clin. Chim. Acta 183 (1989c) 171–182
Schadewaldt, P., Radeck, W., Hammen, H.-W. and Staib W. Transamination and oxidative decarboxylation ofl-isoleucine,l-alloisoleucine and related 2-oxo acids in perfused rat hind limb muscle.Biochim. Biophys. Acta 992 (1989d) 115–123
Scriver, C. R. and Davis, E. Endogenous renal clearance rate of free amino acids in prepubertal children.Pediatrics 36 (1965) 592–598
Skaper, S. D., Molden, D. P. and Seegmiller, J. E. Maple syrup urine disease: branched-chain amino acid concentrations and metabolism in cultured human lymphoblasts.Biochem. Genet. 14 (1976) 527–539
Snyderman, S. E., Norton, P. M., Roitman, E. and Holt, L. E. Maple syrup urine disease, with particular reference to dietotherapy.Pediatrics 34 (1964) 454–472
Tanaka, K. and Rosenberg, L. E. Disorders of branched-chain amino acid and organic acid metabolism. In Stanbury, J. B., Wyngaarden, J. B., Fredrickson, D. S., Goldstein, J. L. and Brown, M. S. (eds.),The Metabolic Basis of Inherited Disease, 5th edn., McGraw-Hill, New York, 1983, pp. 440–473
Taylor, R. T. and Jenkins, W. T. Leucine aminotransferase II. Purification and characterization.J. Biol. Chem. 241 (1966) 4396–4405
Wahlefeld, A. W. and Siedel, J. Creatine and creatinine. In Bergmeyer, H. U. (ed.),Methods of Enzymatic Analysis, vol. VII, Verlag Chemie, Weinheim, 1985, pp. 488–506
Walser, M., Lund, P., Ruderman, N. B. and Coulter, A. W. Synthesis of essential amino acids from their α-keto analogues by perfused rat liver and muscle.J. Clin. Invest. 52 (1973) 2865–2877
Walser, M., Sapir, D. G., Mitch, W. E. and Chan, W. Effects of branched-chain ketoacids in normal subjects and patients. In Walser, M. and Williamson, J. R. (eds.)Metabolism and Clinical Implications of Branched-chain Amino and Ketoacids, Elsevier/North Holland, New York, 1981, pp. 291–299
Weber, F. L., Maddrey, W. C. and Walser, M. Amino acid metabolism of dog jejunum before and during absorption of keto analogues.Am. J. Physiol. 232 (1977) E262-E269
Weinberg, R. B. and Walser, M. Racemization and amination of the keto-analog of isoleucine in the intact dog.Biochem. Med. 17 (1977) 164–172
Wendel, U., Langenbeck, U. and Seakins, J. W. T. Interrelation between the metabolism ofl-isoleucine andl-allo-isoleucine in patients with maple syrup urine disease.Pediatr. Res. 25 (1989) 11–14
Wilkinson, G. N. Statistical estimation in enzyme kinetics.Biochem. J. 80 (1961) 324–332
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Schadewaldt, P., Hammen, H.W., Dalle-Feste, C. et al. On the mechanism ofl-alloisoleucine formation: Studies on a healthy subject and in fibroblasts from normals and patients with maple syrup urine disease. J Inherit Metab Dis 13, 137–150 (1990). https://doi.org/10.1007/BF01799676
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DOI: https://doi.org/10.1007/BF01799676