Influence of progressive tumor growth on glutamine metabolism in skeletal muscle and kidney

M. K. Chen, N. J. Espat, K. I. Bland, E. M. Copeland, W. W. Souba, Courtney Townsend, A. Demetriou, D. M. Morris

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Objective: The effects of progressive malignant growth on glutamine metabolism in skeletal muscle and in kidney were investigated. Summary Background Data: Fast-growing tumors consume considerable quantities of glutamine and lead to a decrease in circulating glutamine concentrations. Methods: Experiments were performed at various stages of tumor growth in rats implanted subcutaneously with the non-metastasizing methylcholanthrene- induced (MCA) fibrosarcoma and in pair-fed non tumor bearing controls. Results: Tumor growth stimulated a twofold increase in hindquarter (muscle) glutamine release, which was not due to an increase in blood flow, but rather to a doubling in the fractional release rate. Consequently, a progressive decrease in skeletal muscle glutamine concentrations was observed over time. Simultaneously, the activity of glutamine synthetase (GS), the principal enzyme of de novo glutamine biosynthesis, increased more than twofold. This increase in muscle GS activity was accompanied by an increase in GS mRNA but the augmentation in GS expression apparently could not match the increased rate of efflux since muscle depletion developed. In rats with large tumors and severe glutamine depletion, GS activity was not elevated. Glutamine feeding increased muscle glutamine concentrations and glutamine synthetase specific activity. Although tumor growth led to the development of mild systemic acidemia, the classic renal adaptations normally observed, i.e., elevated glutaminase activity and accelerated renal glutamine utilization, were not present in acidotic tumor-bearing rats. Instead, renal GS activity was increased in tumor-bearing animals and ammoniagenesis was enhanced, in spite of a reduction in net renal glutamine uptake. Conclusions: These data suggest that marked alterations in muscle and renal glutamine handling occur in the host with cancer; the enhanced muscle glutamine release in conjunction with no increase in renal consumption is consistent with increased glutamine uptake in other organs, most likely the tumor itself and the liver.

Original languageEnglish (US)
Pages (from-to)655-667
Number of pages13
JournalAnnals of Surgery
Volume217
Issue number6
StatePublished - 1993
Externally publishedYes

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Glutamine
Skeletal Muscle
Kidney
Glutamate-Ammonia Ligase
Growth
Neoplasms
Muscles
Glutaminase
Methylcholanthrene
Fibrosarcoma

ASJC Scopus subject areas

  • Surgery
  • Medicine(all)

Cite this

Chen, M. K., Espat, N. J., Bland, K. I., Copeland, E. M., Souba, W. W., Townsend, C., ... Morris, D. M. (1993). Influence of progressive tumor growth on glutamine metabolism in skeletal muscle and kidney. Annals of Surgery, 217(6), 655-667.

Influence of progressive tumor growth on glutamine metabolism in skeletal muscle and kidney. / Chen, M. K.; Espat, N. J.; Bland, K. I.; Copeland, E. M.; Souba, W. W.; Townsend, Courtney; Demetriou, A.; Morris, D. M.

In: Annals of Surgery, Vol. 217, No. 6, 1993, p. 655-667.

Research output: Contribution to journalArticle

Chen, MK, Espat, NJ, Bland, KI, Copeland, EM, Souba, WW, Townsend, C, Demetriou, A & Morris, DM 1993, 'Influence of progressive tumor growth on glutamine metabolism in skeletal muscle and kidney', Annals of Surgery, vol. 217, no. 6, pp. 655-667.
Chen MK, Espat NJ, Bland KI, Copeland EM, Souba WW, Townsend C et al. Influence of progressive tumor growth on glutamine metabolism in skeletal muscle and kidney. Annals of Surgery. 1993;217(6):655-667.
Chen, M. K. ; Espat, N. J. ; Bland, K. I. ; Copeland, E. M. ; Souba, W. W. ; Townsend, Courtney ; Demetriou, A. ; Morris, D. M. / Influence of progressive tumor growth on glutamine metabolism in skeletal muscle and kidney. In: Annals of Surgery. 1993 ; Vol. 217, No. 6. pp. 655-667.
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abstract = "Objective: The effects of progressive malignant growth on glutamine metabolism in skeletal muscle and in kidney were investigated. Summary Background Data: Fast-growing tumors consume considerable quantities of glutamine and lead to a decrease in circulating glutamine concentrations. Methods: Experiments were performed at various stages of tumor growth in rats implanted subcutaneously with the non-metastasizing methylcholanthrene- induced (MCA) fibrosarcoma and in pair-fed non tumor bearing controls. Results: Tumor growth stimulated a twofold increase in hindquarter (muscle) glutamine release, which was not due to an increase in blood flow, but rather to a doubling in the fractional release rate. Consequently, a progressive decrease in skeletal muscle glutamine concentrations was observed over time. Simultaneously, the activity of glutamine synthetase (GS), the principal enzyme of de novo glutamine biosynthesis, increased more than twofold. This increase in muscle GS activity was accompanied by an increase in GS mRNA but the augmentation in GS expression apparently could not match the increased rate of efflux since muscle depletion developed. In rats with large tumors and severe glutamine depletion, GS activity was not elevated. Glutamine feeding increased muscle glutamine concentrations and glutamine synthetase specific activity. Although tumor growth led to the development of mild systemic acidemia, the classic renal adaptations normally observed, i.e., elevated glutaminase activity and accelerated renal glutamine utilization, were not present in acidotic tumor-bearing rats. Instead, renal GS activity was increased in tumor-bearing animals and ammoniagenesis was enhanced, in spite of a reduction in net renal glutamine uptake. Conclusions: These data suggest that marked alterations in muscle and renal glutamine handling occur in the host with cancer; the enhanced muscle glutamine release in conjunction with no increase in renal consumption is consistent with increased glutamine uptake in other organs, most likely the tumor itself and the liver.",
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AU - Chen, M. K.

AU - Espat, N. J.

AU - Bland, K. I.

AU - Copeland, E. M.

AU - Souba, W. W.

AU - Townsend, Courtney

AU - Demetriou, A.

AU - Morris, D. M.

PY - 1993

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N2 - Objective: The effects of progressive malignant growth on glutamine metabolism in skeletal muscle and in kidney were investigated. Summary Background Data: Fast-growing tumors consume considerable quantities of glutamine and lead to a decrease in circulating glutamine concentrations. Methods: Experiments were performed at various stages of tumor growth in rats implanted subcutaneously with the non-metastasizing methylcholanthrene- induced (MCA) fibrosarcoma and in pair-fed non tumor bearing controls. Results: Tumor growth stimulated a twofold increase in hindquarter (muscle) glutamine release, which was not due to an increase in blood flow, but rather to a doubling in the fractional release rate. Consequently, a progressive decrease in skeletal muscle glutamine concentrations was observed over time. Simultaneously, the activity of glutamine synthetase (GS), the principal enzyme of de novo glutamine biosynthesis, increased more than twofold. This increase in muscle GS activity was accompanied by an increase in GS mRNA but the augmentation in GS expression apparently could not match the increased rate of efflux since muscle depletion developed. In rats with large tumors and severe glutamine depletion, GS activity was not elevated. Glutamine feeding increased muscle glutamine concentrations and glutamine synthetase specific activity. Although tumor growth led to the development of mild systemic acidemia, the classic renal adaptations normally observed, i.e., elevated glutaminase activity and accelerated renal glutamine utilization, were not present in acidotic tumor-bearing rats. Instead, renal GS activity was increased in tumor-bearing animals and ammoniagenesis was enhanced, in spite of a reduction in net renal glutamine uptake. Conclusions: These data suggest that marked alterations in muscle and renal glutamine handling occur in the host with cancer; the enhanced muscle glutamine release in conjunction with no increase in renal consumption is consistent with increased glutamine uptake in other organs, most likely the tumor itself and the liver.

AB - Objective: The effects of progressive malignant growth on glutamine metabolism in skeletal muscle and in kidney were investigated. Summary Background Data: Fast-growing tumors consume considerable quantities of glutamine and lead to a decrease in circulating glutamine concentrations. Methods: Experiments were performed at various stages of tumor growth in rats implanted subcutaneously with the non-metastasizing methylcholanthrene- induced (MCA) fibrosarcoma and in pair-fed non tumor bearing controls. Results: Tumor growth stimulated a twofold increase in hindquarter (muscle) glutamine release, which was not due to an increase in blood flow, but rather to a doubling in the fractional release rate. Consequently, a progressive decrease in skeletal muscle glutamine concentrations was observed over time. Simultaneously, the activity of glutamine synthetase (GS), the principal enzyme of de novo glutamine biosynthesis, increased more than twofold. This increase in muscle GS activity was accompanied by an increase in GS mRNA but the augmentation in GS expression apparently could not match the increased rate of efflux since muscle depletion developed. In rats with large tumors and severe glutamine depletion, GS activity was not elevated. Glutamine feeding increased muscle glutamine concentrations and glutamine synthetase specific activity. Although tumor growth led to the development of mild systemic acidemia, the classic renal adaptations normally observed, i.e., elevated glutaminase activity and accelerated renal glutamine utilization, were not present in acidotic tumor-bearing rats. Instead, renal GS activity was increased in tumor-bearing animals and ammoniagenesis was enhanced, in spite of a reduction in net renal glutamine uptake. Conclusions: These data suggest that marked alterations in muscle and renal glutamine handling occur in the host with cancer; the enhanced muscle glutamine release in conjunction with no increase in renal consumption is consistent with increased glutamine uptake in other organs, most likely the tumor itself and the liver.

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