The Role of the Urea Cycle and Polyamines in Albumin Synthesis

Authors

  • Murray Oratz,

    Corresponding author
    1. Radioisotope Service, New York Veterans Administration Medical Center and Department of Biochemistry, New York University Dental Center, New York, New York 10010; and Department of Medicine, New York University Medical Center, New York, New York 10016
    • Murray Oratz, Ph.D., Nuclear Medicine Service (115), Veterans Administration Medical Center, 1st Avenue at E. 24th Street, New York, New York 10010.
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  • Marcus A. Rothschild,

    1. Radioisotope Service, New York Veterans Administration Medical Center and Department of Biochemistry, New York University Dental Center, New York, New York 10010; and Department of Medicine, New York University Medical Center, New York, New York 10016
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  • Sidney S. Schreiber,

    1. Radioisotope Service, New York Veterans Administration Medical Center and Department of Biochemistry, New York University Dental Center, New York, New York 10010; and Department of Medicine, New York University Medical Center, New York, New York 10016
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  • Alvin Burks,

    1. Radioisotope Service, New York Veterans Administration Medical Center and Department of Biochemistry, New York University Dental Center, New York, New York 10010; and Department of Medicine, New York University Medical Center, New York, New York 10016
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  • Joseph Mongelli,

    1. Radioisotope Service, New York Veterans Administration Medical Center and Department of Biochemistry, New York University Dental Center, New York, New York 10010; and Department of Medicine, New York University Medical Center, New York, New York 10016
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  • Barbara Matarese

    1. Radioisotope Service, New York Veterans Administration Medical Center and Department of Biochemistry, New York University Dental Center, New York, New York 10010; and Department of Medicine, New York University Medical Center, New York, New York 10016
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  • A portion of these results has been reported in preliminary form at the 33rd Annual Meeting of the American Association for the Study of Liver Diseases, November, 1982

Abstract

Albumin synthesis is stimulated by those amino acids which increase urea synthesis and membrane bound polysome aggregation. Ornithine, an amino acid not incorporated into protein and produced from arginine in the urea cycle, is an albumin-stimulating amino acid and is the precursor of the polyamines, and we have shown that the polyamine spermine promotes bound polysome aggregation. To test the concept that ureogenesis with its generation of ornithine might play a key role in albumin synthesis regulation via the polyamine pathway, isolated livers from fasted donors were perfused with ornithine, α-difluoromethyl ornithine (DFMO), and spermine. In control experiments, albumin synthesis was 13.4 ± 0.8 mg per 100 gm liver per hr and polysome aggregation was 47%. These were increased in the presence of ornithine (26.0 ± 2.6 mg and 59%); if the livers were preperfused with DFMO before the addition of ornithine, then the expected increase in albumin synthesis and polysome reaggregation did not occur (16.3 ± 1.4 mg and 47%). However, if spermine was present with DFMO during the preperfusion, then the addition of ornithine had the expected effect (albumin synthesis = 26.1 ±1.2 mg and polysome aggregation = 62%). This suggests that if the ornithine to putrescine pathway is blocked, ornithine does not stimulate albumin synthesis and offers support to the concepts that (a) ornithine stimulation of albumin production is via polyamine synthesis and (b) that the urea cycle plays a more important role in protein metabolism than simply the pathway for nitrogen disposal.

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