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Effect of Echinococcus multilocularis on the origin of acetyl-CoA entering the tricarboxylic acid cycle in host liver

Published online by Cambridge University Press:  12 April 2024

C. Kepron ,
M. Novak  and
B.J. Blackburn
C. Kepron
Affiliation:
Department of Biology, University of Winnipeg, Winnipeg, Manitoba, Canada R3B 2E9
M. Novak*
Affiliation:
Department of Biology, University of Winnipeg, Winnipeg, Manitoba, Canada R3B 2E9
B.J. Blackburn
Affiliation:
Department of Chemistry, University of Winnipeg, Winnipeg, Manitoba, Canada R3B 2E9
*
*Author for correspondence Fax: 204 774 4134 Email: m.novak@uwinnipeg.ca
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Abstract

Carbon-13 nuclear magnetic resonance (NMR) spectroscopy was employed to investigate alterations in hepatic carbohydrate metabolism in Meriones unguiculatus infected with Echinococcus multilocularis. Following portal vein injections of an equimolar mixture of ]#x005B;1,2-13C2]acetate and [3-13C]lactate, perchloric acid extracts of the livers were prepared and NMR spectra obtained. Isotopomer analysis using glutamate resonances in these spectra showed that the relative contributions of endogenous and exogenous substrates to the acetyl-CoA entering the tricarboxylic acid cycle differed significantly between infected and control groups. The mole fraction of acetyl-CoA that was derived from endogenous, unlabelled sources (FU) was 0.50±0.10 in controls compared to 0.34±0.04 in infected animals. However, the fraction of acetyl-CoA derived from [3-13C]lactate (FLL) was larger in livers of infected animals than those from controls with values of 0.27±0.04 and 0.18±0.04, respectively. Similarly, the fraction of acetyl-CoA derived from [1,2-13C2]acetate (FLA) was larger in livers of infected animals compared to those in controls; the fractions were 0.38±0.01 and 0.32±0.07, respectively. The ratio of FLA:FLL was significantly smaller in the infected group with a value of 1.42±0.18 compared to 1.74±0.09 for the controls. These results indicate that alveolar hydatid disease has a pronounced effect on the partitioning of substrates within the pathways of carbohydrate metabolism in the host liver.

Type
Review Article
Information
Journal of Helminthology , Volume 76 , Issue 1 , March 2002 , pp. 31 - 36
Copyright
Copyright © Cambridge University Press 2002

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References

Baranyai, J.M. & Blum, J.J. (1989) Quantitative analysis of intermediary metabolism in rat hepatocytes incubated in the presence and absence of ethanol with a substrate mixture including ketoleucine. Biochemical Journal 258, 121–140.CrossRefGoogle ScholarPubMed
Blackburn, B.J., Buist, R., Hudspeth, C. & Novak, M. (1993) Phosphorus metabolites of liver from mice infected with Hymenolepis diminuta . International Journal for Parasitology 23, 95–103.CrossRefGoogle Scholar
Crabtree, B., Gordon, M.-J. & Christie, S.L. (1990) Measurement of the rates of acetyl-CoA hydrolysis and synthesis from acetate in rat hepatocytes and the role of these fluxes in substrate cycling. Biochemical Journal 270, 219–225.CrossRefGoogle ScholarPubMed
Des Rosiers, C. David, F., Garneau, M. & Brunengraber, H. (1991) Nonhomogenous labeling of liver mitochondrial acetyl-CoA. Journal of Biological Chemistry 266, 1574–1578.CrossRefGoogle ScholarPubMed
Fafournoux, P., Demigne, C. & Remesy, C. (1985) Carrier-mediated uptake of lactate in rat hepatocytes. Journal of Biological Chemistry 260, 292–299.CrossRefGoogle ScholarPubMed
Goodman, M.N. & Ruderman, N.B. (1980) Starvation in the rat. I. Effect of age and obesity on organ weights, RNA, DNA and protein. American Journal of Physiology 239, E269–E276.Google Scholar
Hegarty, P.V.J. & Kim, K.O. (1981) Effect of starvation on tissues from the young of four species, with emphasis on the number and diameter of skeletal muscle fibers. Pediatric Research 15, 128–132.CrossRefGoogle Scholar
Hellerstein, M.K. & Munro, H.N. (1994) Interaction of liver, muscle and adipose tissue in the regulation of metabolism in response to nutritional and other factors, pp. 1169–1191 in Arias, I.M., Boyer, J.L., Fausto, N., Jakoby, W.B., Schachter, D.A. & Shafritz, D.A. (Eds) The liver: biology and pathobiology. 3rd edn, New York, Raven Press.Google Scholar
Hers, H.-G. (1990) Mechanisms of blood glucose homeostasis. Journal of Inherited Metabolic Disease 13, 395–410.CrossRefGoogle ScholarPubMed
Jackson, V.N. & Halestrap, A.P. (1996) The kinetics, substrate and inhibitor specificity of the monocarboxylate (lactate) transporter of rat liver cells determined using the fluorescent intracellular pH indicator, 2′,7′-bis(carboxyethyl)-5(6)-carboxyfluorescein. Journal of Biological Chemistry 271, 861–868.CrossRefGoogle Scholar
Kummel, L. (1987) Mitochondrial pyruvate carrier–a possible link between gluconeogenesis and ketogenesis in the liver. Biosciences Reports 7, 593–597.CrossRefGoogle ScholarPubMed
Malloy, C.R., Thompson, J.R., Jeffrey, F.M.H. & Sherry, A.D. (1990) Contribution of exogenous substrates to acetyl coenzyme A: measurement by 13C NMR under non-steady state conditions. Biochemistry 29, 6756–6761.CrossRefGoogle ScholarPubMed
Metcalfe, H.K., Monson, J.P., Cohen, R.D. & Padgham, C. (1988) Enhanced carrier-mediated lactate entry into isolated hepatocytes from starved and diabetic rats. Journal of Biological Chemistry 263, 19505–19509.CrossRefGoogle ScholarPubMed
Modha, A., Novak, M. & Blackburn, B.J. (1997) Treatment of experimental echinococcosis with albendazole: a 1H NMR spectroscopic study. Canadian Journal of Zoology 75, 198–204.CrossRefGoogle Scholar
Morand, C., Remesy, C. & Demigne, C. (1993) Fatty acids are potent modulators of lactate utilization in isolated hepatocytes from fed rats. American Journal of Physiology 264, E816–E823.Google ScholarPubMed
Novak, M., Marat, K., Johnson, L. & Blackburn, B.J. (1989) 1H and 13C NMR studies of serum from normal and Echinococcus multilocularis-infected jirds. International Journal for Parasitology 19, 395–400.CrossRefGoogle ScholarPubMed
Novak, M., Modha, A. & Blackburn, B.J. (1993) Metabolic alterations in organs of Meriones unguiculatus infected with Echinococcus multilocularis . Comparative Biochemistry and Physiology 105B, 517–521.Google Scholar
Novak, M., Modha, A., Lee, J., Buist, R. ]#x0026; Blackburn, B.J. (1995) Metabolism of D-[1-13C]glucose in livers of Meriones unguiculatusEchinococcus multilocularis . Canadian Journal of Zoology 73, 58–66.CrossRefGoogle Scholar
Poole, R.C. & Halestrap, A.P. (1993) Transport of lactate and other monocarboxylates across mammalian plasma membranes. American Journal of Physiology 264, C761–C782.CrossRefGoogle ScholarPubMed
Rabkin, M. & Blum, J.J. (1985) Quantitative analysis of intermediary metabolism in hepatocytes incubated in the presence and absence of glucagon with a substrate mixture containing glucose, ribose, fructose, alanine and acetate. Biochemical Journal 225, 761–786.CrossRefGoogle ScholarPubMed
Schoen, J., Novak, M. ]#x0026; Blackburn, B.J. (1999) Hepatic [2-13C]acetate metabolism by jirds infected with Echinococcus multilocularis . Journal of Helminthology 73, 245–250.CrossRefGoogle Scholar
Seifter, S. & Englard, S. (1994) Energy metabolism, pp. 323–364 in Arias, I.M., Boyer, J.L., Fausto, N., Jakoby, W.B., Schachter, D.A. & Shafritz, D.A. (Eds) The liver: biology and pathobiology. 3rd edn, New York, Raven Press.Google Scholar
Sherry, A.D., Malloy, C.R., Zhao, P. & Thompson, J.R. (1992) Alterations in substrate utilization in the reperfused myocardium: a direct analysis by 13C NMR. Biochemistry 31, 4833–4837.CrossRefGoogle ScholarPubMed
Snoswell, A.M., Trimble, R.P., Fishlock, R.C., Storer, G.B. & Topping, D.L. (1982) Metabolic effects of acetate in perfused rat liver: studies on ketogenesis, glucose output, lactate uptake and lipogenesis. Biochimica et Biophysica Acta 716, 290–297.CrossRefGoogle ScholarPubMed
Van den Burghe, G. (1991) The role of the liver in metabolic homeostasis: implications for inborn errors of metabolism. Journal of Inherited Metabolic Disease 14, 407–420.CrossRefGoogle Scholar
Zhang, Y., Agarawal, K.C., Beylot, M., Soloviev, M., David, F., Reider, M., Anderson, V., Tserng, K.-T. & Brunengraber, H. (1994) Nonhomogenous labeling of liver extra-mitochondrial acetyl-CoA. Journal of Biological Chemistry 269, 11025–11029.CrossRefGoogle ScholarPubMed