Hostname: page-component-cd9895bd7-gxg78 Total loading time: 0 Render date: 2024-12-26T06:51:11.219Z Has data issue: false hasContentIssue false

Metabolism of ketone bodies in pregnant sheep

Published online by Cambridge University Press:  09 March 2007

D. W. Pethick
Affiliation:
Biochemistry Department, ARC Institute of Animal Physiology, Babraham, Cambridge CB2 4AT
D. B. Lindsay
Affiliation:
Biochemistry Department, ARC Institute of Animal Physiology, Babraham, Cambridge CB2 4AT
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

1. A combination of isotope-dilution and arteriovenous-difference techniques was used to determine the significance of ketones to energy homoeostasis in fasted pregnant ewes.

2. There was incomplete interconversion of D(−) 3-hydroxybutyrate (3HB) and acetoacetate (AcAc) and therefore neither entry rate nor oxidation of total ketone bodies could be estimated by assuming circulating ketone bodies represent a single metabolic compartment. Total ketone body metabolism was satisfactorily summarized using a three-compartment model. In fasted pregnant ewes the mean entry rate of total ketones was 1 mmol/h per kg body-weight and of the ketones entering the circulation 87% were promptly oxidized to carbon dioxide accounting for 30% of the total COa production.

3. Ketone bodies are readily utilized by hind-limb skeletal muscle such that if completely oxidized, 18±4 and 48±3% of the oxygen utilized could be accounted for in fed and fasted pregnant ewes respectively. For both 3HB and AcAc there was a hyperbolic relationship between utilization and arterial concentration. The apparent Michaelis constant (Km) values were 0·55 and 1–42 mM respectively and the maximum velocity (Vmax) 2·9 and 5·6 mmol/h per kg muscle. The arterial concentration of AcAc is always below the Km value and this limits the utilization rate. The D(−) 3HB concentration, however, may surpass that required for maximum utilization and ketoacidosis may be a consequence of this.

4. A two-compartment model was used to analyse ketone body metabolism by hind-limb skeletal muscle. The results suggested substantial intercon version and production of AcAc and 3HB.

5. The pregnant uterus utilized 3HB which if completely oxidized accounted for 12±2 (fed) and 25±4 (fasted) % of its O2 consumption. At least 64% of the net 3HB utilized was oxidized. AcAc was not utilized in significant quantities.

Type
Papers on General Nutrition
Copyright
Copyright © The Nutrition Society 1982

References

REFERENCES

Alexander, D. P., Britton, H. G., Cohen, N. H. & Nixon, D. A. (1969). In Foetal Autonomy, p. 95 [Wolstenholm, G. E. W. and O'Connor, M., editors]. London: Churchill.Google Scholar
Atkins, G. L. (1969). Multicompartment Models for Biological Systems. London: Methuen & Co. Ltd.Google Scholar
Balasse, E. O. (1979). Metabolism 28, 41.CrossRefGoogle ScholarPubMed
Balasse, E. O. & Delcroix, C. (1980). Metabolism 29, 395.CrossRefGoogle Scholar
Barton, R. N. (1980). Metabolism 29, 392.CrossRefGoogle Scholar
Behnke, A. R. (1964). In Fat as a Tissue, p. 379 [Rodahl, R. and Issekutz, B., editors]. New York: McGraw-Hill Book Co.Google Scholar
Berger, M., Kemmer, F. W., Goodman, M. N., Zimmerman-Telshcow, H. & Ruderman, N. B. (1978). In Biochemical and Clinical Aspects of Ketone Body Metabolism, p. 193 [Söling, H. S. and Seufert, C. D., editors]. Stuttgart: Georg Thieme Publishers.Google Scholar
Bergman, E. N. (1971). J. Dairy Sci. 54, 936.CrossRefGoogle Scholar
Bergman, E. N. & Kon, E. (1964). Am. J. Physiol. 206, 449.CrossRefGoogle Scholar
Bergman, E. N., Kon, E. & Katz, M. L. (1963). Am. J. Physiol. 205, 658.CrossRefGoogle Scholar
Bliss, C. I. (1970). Statistics in Biology, vol. 2. New York and London: McGraw-Hill.Google Scholar
Comline, R. S. & Silver, M. (1974). Br. med. Bull. 31, 25.CrossRefGoogle Scholar
Domanski, A., Lindsay, D. B. & Setchell, B. P. (1974). J. Physiol., Lond. 242, 28P.Google Scholar
Edwards, E. M., Rattenbury, J. M., Varnam, G. C. F., Dhand, U. K., Jeacock, M. K. & Shepherd, D. A. L. (1977). Biochim. biophys. Acta 497, 133.CrossRefGoogle Scholar
Hagenfeldt, H. & Wahren, J. (1971). In Muscle Metabolism During Exercise, p. 153 [Pernow, B. and Sutton, B., editors]. New York and London: Plenum Press.CrossRefGoogle ScholarPubMed
Hall, L. M. (1962). Anal. Biochem. 3, 75.CrossRefGoogle Scholar
Jarrett, I. G., Filsell, O. H. & Ballard, F. J. (1974). Horm. Metab. Res. Suppl 4, 111.Google Scholar
Jarrett, I. G., Filsell, O. H. & Ballard, F. J. (1976). Metabolism 25, 523.CrossRefGoogle Scholar
Kaufman, C. F. & Bergman, E. N. (1971). Am. J. Physiol. 22, 967.CrossRefGoogle Scholar
Keller, V., Cherrington, A. D. & Liljenquist, J. E. (1978). Am. J. Physiol. 235, E238.Google Scholar
Koundakjian, P. P. & Snoswell, A. M. (1970). Biochem. J. 119, 49.CrossRefGoogle Scholar
Krebs, H. A. (1966). Adv. Enz. Reg. 4, 339.CrossRefGoogle Scholar
Krebs, H. A., Williamson, D. H., Bates, M. W., Page, A. N. & Hawkins, R. A. (1971). Adv. Enz. Reg. 9, 389.Google Scholar
LaNoue, K., Kieklas, W. J. & Williamson, J. R. (1970). J. biol. Chem. 245, 102.CrossRefGoogle Scholar
Leng, R. A. (1966). Res. vet. Sci. 7, 180.CrossRefGoogle Scholar
Lindsay, D. B. & Brown, R. D. (1966). Biochem. J. 100, 589.CrossRefGoogle Scholar
Lindsay, D. B. & Setchell, B. P. (1976). J. Physiol. 259, 801.CrossRefGoogle Scholar
McGarry, J. E., Guest, M. J. & Foster, D. W. (1970). J. biol. Chem. 245, 4382.CrossRefGoogle Scholar
Mann, J. & Gurpide, E. (1966). J. clin. Endocr. 26, 1346.CrossRefGoogle Scholar
Meschia, G., Battaglia, F. C., Hay, W. W. & Sparkes, J. W. (1979). Fedn. Proc., Fedn. Am. Socs. exp. Biol. 39, 245.Google Scholar
Morriss, F. H., Boyd, R. D. H., Makowski, E. L., Meschia, G. & Battaglia, F. C. (1974). Proc. Soc. exp. Biol. Med. 145, 879.CrossRefGoogle Scholar
Nolan, J. V., Norton, B. W. & Leng, R. W. (1976). Br. J. Nutr. 35, 127.CrossRefGoogle Scholar
Pethick, D. W. & Lindsay, D. B. (1982). Br. J. Nutr. 48, 319.CrossRefGoogle Scholar
Pethick, D. W., Lindsay, D. B., Barker, P. J. & Northrop, A. J. (1981). Br. J. Nutr. 45, 97.CrossRefGoogle Scholar
Pethick, D. W., Lindsay, D. B., Barker, P. J. & Northrop, A. J. (1983). Br. J. Nutr. (In the Press.)Google Scholar
Reichard, G. A., Haff, A. C., Skutches, C. L., Paul, P., Holroyde, C. P. & Owen, O. E. (1979). J. clin. Invest. 63, 619.CrossRefGoogle Scholar
Ruderman, N. B. & Goodman, M. N. (1973). Am. J. Physiol. 224, 1391.CrossRefGoogle Scholar
Sachan, D. S. & Davis, C. L. (1967). J. Dairy Sci. 50, 1273.CrossRefGoogle Scholar
Setchell, B. P., Bassett, J. M., Hinks, N. T. & Graham, N. McC. (1972). Q. Jl. expt. Physiol. 57, 257.CrossRefGoogle Scholar
Silver, M. (1976). In Foetal Physiology and Medicine, p. 173 [Beard, R. W. and Nathanielsz, P. W., editors]. London: Saunders.Google Scholar
Watson, H. R. & Lindsay, D. B. (1972). Biochem. J. 128, 53.CrossRefGoogle Scholar
Whitelaw, F. G., Brockway, J. M. & Reid, R. S. (1972). Q. Jl. expt. Physiol. 57, 37.CrossRefGoogle Scholar
Wicklmayr, M. & Dietze, G. (1979). Horm. Metab. Res. 11, 1.CrossRefGoogle Scholar
Wolff, J. E. & Bergman, E. N. (1972). Am. J. Physiol. 223, 447.CrossRefGoogle Scholar