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Amendment history:
  • Errata (January 1974)

Research Article Free access | 10.1172/JCI107483

Synthesis of Essential Amino Acids from Their α-Keto Analogues by Perfused Rat Liver and Muscle

Mackenzie Walser, Patricia Lund, Neil B. Ruderman, and A. W. Coulter

Metabolic Research Laboratory, Nuffield Department of Medicine, Oxford University, Oxford, England

Department of Pharmacology and Experimental Therapeutics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Joslin Research Laboratories, Harvard University Medical School, Boston, Massachusetts 02215

Find articles by Walser, M. in: PubMed | Google Scholar

Metabolic Research Laboratory, Nuffield Department of Medicine, Oxford University, Oxford, England

Department of Pharmacology and Experimental Therapeutics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Joslin Research Laboratories, Harvard University Medical School, Boston, Massachusetts 02215

Find articles by Lund, P. in: PubMed | Google Scholar

Metabolic Research Laboratory, Nuffield Department of Medicine, Oxford University, Oxford, England

Department of Pharmacology and Experimental Therapeutics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Joslin Research Laboratories, Harvard University Medical School, Boston, Massachusetts 02215

Find articles by Ruderman, N. in: PubMed | Google Scholar

Metabolic Research Laboratory, Nuffield Department of Medicine, Oxford University, Oxford, England

Department of Pharmacology and Experimental Therapeutics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Joslin Research Laboratories, Harvard University Medical School, Boston, Massachusetts 02215

Find articles by Coulter, A. in: PubMed | Google Scholar

Published November 1, 1973 - More info

Published in Volume 52, Issue 11 on November 1, 1973
J Clin Invest. 1973;52(11):2865–2877. https://doi.org/10.1172/JCI107483.
© 1973 The American Society for Clinical Investigation
Published November 1, 1973 - Version history
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Abstract

Most essential amino acids can be replaced by their α-keto-analogues in the diet. These ketoacids have therefore been proposed as substitutes for dietary protein. In order to determine their fate in tissues of normal animals, isolated rat liver and hindquarter (muscle) preparations were perfused with keto-analogues of valine, leucine, isoleucine, methionine, or phenylalanine. When perfused at 1.5-2.0 mM, all five compounds were utilized rapidly by the liver of 48-h starved rats, at rates varying from 49 to 155 μmol/h per 200g rat. The corresponding amino acids appeared in the medium in significantly increased concentrations. Perfusion with phenylpyruvate also led to the appearance of tyrosine. Urea release was unaltered. Measurement of metabolite concentrations in freeze-clamped liver revealed two abnormalities, particularly at ketoacid concentrations of 5 mM or above: a large increase in α-ketoglutarate, and a moderate to marked decrease in tissue glutamine. This decrease was quantitatively sufficient to account for nitrogen appearing in newly synthesized amino acids.

Isolated hindquarters of fed rats were perfused with the same ketoacids at concentrations of 1.3-8.0 mM. All were utilized at rates varying from 1.4 to 7.0 μmol/h per g muscle perfused. The corresponding amino acids were released at greatly increased rates. Alanine and glutamate levels fell in some perfusions, but the principal nitrogen donor in muscle was not identified; the content of glutamine in tissue, and its rate of release into the perfusate remained constant.

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