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. 1986 Oct 1;239(1):121–125. doi: 10.1042/bj2390121

Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages.

P Newsholme, R Curi, S Gordon, E A Newsholme
PMCID: PMC1147248  PMID: 3800971

Abstract

Maximum activities of some key enzymes of metabolism were studied in elicited (inflammatory) macrophages of the mouse and lymph-node lymphocytes of the rat. The activity of hexokinase in the macrophage is very high, as high as that in any other major tissue of the body, and higher than that of phosphorylase or 6-phosphofructokinase, suggesting that glucose is a more important fuel than glycogen and that the pentose phosphate pathway is also important in these cells. The latter suggestion is supported by the high activities of both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. However, the rate of glucose utilization by 'resting' macrophages incubated in vitro is less than the 10% of the activity of 6-phosphofructokinase: this suggests that the rate of glycolysis is increased dramatically during phagocytosis or increased secretory activity. The macrophages possess higher activities of citrate synthase and oxoglutarate dehydrogenase than do lymphocytes, suggesting that the tricarboxylic acid cycle may be important in energy generation in these cells. The activity of 3-oxoacid CoA-transferase is higher in the macrophage, but that of 3-hydroxybutyrate dehydrogenase is very much lower than those in the lymphocytes. The activity of carnitine palmitoyltransferase is higher in macrophages, suggesting that fatty acids as well as acetoacetate could provide acetyl-CoA as substrate for the tricarboxylic acid cycle. No detectable rate of acetoacetate or 3-hydroxybutyrate utilization was observed during incubation of resting macrophages, but that of oleate was 1.0 nmol/h per mg of protein or about 2.2% of the activity of palmitoyltransferase. The activity of glutaminase is about 4-fold higher in macrophages than in lymphocytes, which suggests that the rate of glutamine utilization could be very high. The rate of utilization of glutamine by resting incubated macrophages was similar to that reported for rat lymphocytes, but was considerably lower than the activity of glutaminase.

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Selected References

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  1. Ardawi M. S., Newsholme E. A. Glutamine metabolism in lymphocytes of the rat. Biochem J. 1983 Jun 15;212(3):835–842. doi: 10.1042/bj2120835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ardawi M. S., Newsholme E. A. Maximum activities of some enzymes of glycolysis, the tricarboxylic acid cycle and ketone-body and glutamine utilization pathways in lymphocytes of the rat. Biochem J. 1982 Dec 15;208(3):743–748. doi: 10.1042/bj2080743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ardawi M. S., Newsholme E. A. Metabolism in lymphocytes and its importance in the immune response. Essays Biochem. 1985;21:1–44. [PubMed] [Google Scholar]
  4. Babior B. M. Oxygen-dependent microbial killing by phagocytes (first of two parts). N Engl J Med. 1978 Mar 23;298(12):659–668. doi: 10.1056/NEJM197803232981205. [DOI] [PubMed] [Google Scholar]
  5. Bonney R. J., Naruns P., Davies P., Humes J. L. Antigen-antibody complexes stimulate the synthesis and release of prostaglandins by mouse peritoneal macrophages. Prostaglandins. 1979 Oct;18(4):605–616. doi: 10.1016/0090-6980(79)90027-3. [DOI] [PubMed] [Google Scholar]
  6. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  7. Brand K., Williams J. F., Weidemann M. J. Glucose and glutamine metabolism in rat thymocytes. Biochem J. 1984 Jul 15;221(2):471–475. doi: 10.1042/bj2210471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Challiss R. A., Lozeman F. J., Leighton B., Newsholme E. A. Effects of the beta-adrenoceptor agonist isoprenaline on insulin-sensitivity in soleus muscle of the rat. Biochem J. 1986 Jan 15;233(2):377–381. doi: 10.1042/bj2330377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cohn Z. A. Activation of mononuclear phagocytes: fact, fancy, and future. J Immunol. 1978 Sep;121(3):813–816. [PubMed] [Google Scholar]
  10. Cohn Z. A. The isolation and cultivation of mononuclear phagocytes. Methods Enzymol. 1974;32:758–765. doi: 10.1016/0076-6879(74)32079-4. [DOI] [PubMed] [Google Scholar]
  11. Cooney G. J., Taegtmeyer H., Newsholme E. A. Tricarboxylic acid cycle flux and enzyme activities in the isolated working rat heart. Biochem J. 1981 Dec 15;200(3):701–703. doi: 10.1042/bj2000701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Crabtree B., Newsholme E. A. The activities of phosphorylase, hexokinase, phosphofructokinase, lactate dehydrogenase and the glycerol 3-phosphate dehydrogenases in muscles from vertebrates and invertebrates. Biochem J. 1972 Jan;126(1):49–58. doi: 10.1042/bj1260049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. DULBECCO R., VOGT M. Plaque formation and isolation of pure lines with poliomyelitis viruses. J Exp Med. 1954 Feb;99(2):167–182. doi: 10.1084/jem.99.2.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goldstein L., Newsholme E. A. The formation of alanine from amino acids in diaphragm muscle of the rat. Biochem J. 1976 Feb 15;154(2):555–558. doi: 10.1042/bj1540555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gordon S. Biology of the macrophage. J Cell Sci Suppl. 1986;4:267–286. doi: 10.1242/jcs.1986.supplement_4.16. [DOI] [PubMed] [Google Scholar]
  16. Gudewicz P. W., Filkins J. P. Glycogen metabolism in inflammatory macrophages. J Reticuloendothel Soc. 1976 Aug;20(2):147–157. [PubMed] [Google Scholar]
  17. Hammer J. A., 3rd, Rannels D. E. Protein turnover in pulmonary macrophages. Utilization of amino acids derived from protein degradation. Biochem J. 1981 Jul 15;198(1):53–65. doi: 10.1042/bj1980053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hawkins R. A., Williamson D. H., Krebs H. A. Ketone-body utilization by adult and suckling rat brain in vivo. Biochem J. 1971 Mar;122(1):13–18. doi: 10.1042/bj1220013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Karnovsky M. L., Lazdins J. K. Biochemical criteria for activated macrophages. J Immunol. 1978 Sep;121(3):809–813. [PubMed] [Google Scholar]
  20. Kiyotaki C., Peisach J., Bloom B. R. Oxygen metabolism in cloned macrophage cell lines: glucose dependence of superoxide production, metabolic and spectral analysis. J Immunol. 1984 Feb;132(2):857–866. [PubMed] [Google Scholar]
  21. Knight B. L., Patel D. D., Soutar A. K. The regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity, cholesterol esterification and the expression of low-density lipoprotein receptors in cultured monocyte-derived macrophages. Biochem J. 1983 Feb 15;210(2):523–532. doi: 10.1042/bj2100523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  23. Leighton B., Budohoski L., Lozeman F. J., Challiss R. A., Newsholme E. A. The effect of prostaglandins E1, E2 and F2 alpha and indomethacin on the sensitivity of glycolysis and glycogen synthesis to insulin in stripped soleus muscles of the rat. Biochem J. 1985 Apr 1;227(1):337–340. doi: 10.1042/bj2270337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lund P. Glutamine metabolism in the rat. FEBS Lett. 1980 Aug 25;117 (Suppl):K86–K92. doi: 10.1016/0014-5793(80)80573-4. [DOI] [PubMed] [Google Scholar]
  25. Newsholme E. A., Brand K., Lang J., Stanley J. C., Williams T. The maximum activities of enzymes that are involved in substrate cycles in liver and muscle of obese mice. Biochem J. 1979 Aug 15;182(2):621–624. doi: 10.1042/bj1820621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Newsholme E. A., Crabtree B., Ardawi M. S. Glutamine metabolism in lymphocytes: its biochemical, physiological and clinical importance. Q J Exp Physiol. 1985 Oct;70(4):473–489. doi: 10.1113/expphysiol.1985.sp002935. [DOI] [PubMed] [Google Scholar]
  27. Newsholme E. A., Crabtree B., Ardawi M. S. The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells. Biosci Rep. 1985 May;5(5):393–400. doi: 10.1007/BF01116556. [DOI] [PubMed] [Google Scholar]
  28. Newsholme E. A., Lang J., Relman A. S. Control of rate of glutamine metabolism in the kidney. Contrib Nephrol. 1982;31:1–4. doi: 10.1159/000406607. [DOI] [PubMed] [Google Scholar]
  29. Read G., Crabtree B., Smith G. H. The activities of 2-oxoglutarate dehydrogenase and pyruvate dehydrogenase in hearts and mammary glands from ruminants and non-ruminants. Biochem J. 1977 May 15;164(2):349–355. doi: 10.1042/bj1640349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Simon L. M., Robin E. D., Phillips J. R., Acevedo J., Axline S. G., Theodore J. Enzymatic basis for bioenergetic differences of alveolar versus peritoneal macrophages and enzyme regulation by molecular O2. J Clin Invest. 1977 Mar;59(3):443–448. doi: 10.1172/JCI108658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sugden P. H., Newsholme E. A. Activities of citrate synthase, NAD+-linked and NADP+-linked isocitrate dehydrogenases, glutamate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in nervous tissues from vertebrates and invertebrates. Biochem J. 1975 Jul;150(1):105–111. doi: 10.1042/bj1500105. [DOI] [PMC free article] [PubMed] [Google Scholar]

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