Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-25T17:53:49.822Z Has data issue: false hasContentIssue false
  • English
  • Français

Genetic control of metabolism: enzyme studies of the obese and adipose mutants in the mouse

Published online by Cambridge University Press:  14 April 2009

Grahame Bulfield
Grahame Bulfield
Affiliation:
Institute of Animal Genetics, University of Edinburgh, Edinburgh EH9 3JN
Rights & Permissions [Opens in a new window]

Summary

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.

The activity of several enzymes has been determined in the livers of homozygous obese and adipose mice, their normal litter-mates, and phenocopies induced in normal mice by aurothioglucose (ATG) injections.

Obese, adipose and ATG mice had higher activities of ATP citrate lyase, malic enzyme (NADP malate dehydrogenase) and pyruvate kinase than normal mice. Heterozygote activities are indistinguishable from wild-type. There was no difference between normal and fat litter-mates in the activity of malate dehydrogenase (NAD-linked), lactate dehydrogenase, isocitrate dehydrogenase and fumarase.

Crosses between mice doubly heterozygous for roth the ad and ob genes produced offspring that were only ‘fat’ or ‘normal’ and no offspring could be phenotypically recognized as the double mutant, either physically or in terms of ATP citrate lyase activity.

Gas–liquid chromatography of the fatty acids of the depot fat showed no differences between any of the types of litter-mate.

The alterations found in enzyme activity in obese and adipose mice are compared to several other enzyme activity differences reported in the literature for obese mice. These are discussed in relation to genetical criteria that may be estarlished to assess, from quantitative data, whether an enzyme is the site of the primary lesion in a mutant pheno-type. Some general observations are made on genetics and the control of metabolism.

Type
Research Article
Information
Genetics Research , Volume 20 , Issue 1 , August 1972 , pp. 51 - 64
Copyright
Copyright © Cambridge University Press 1972

References

REFERENCES

Chang, H. C., Seidman, I., Teebor, G. & Lane, M. D. (1967). Liver acetyl CoA carboxylase and fatty acid synthetase: relative activities in the normal state and hereditary obesity. Biochemical and Biophysical Research Communication 28, 682–686.CrossRefGoogle ScholarPubMed
Coleman, D. L. (1962). Effect of genic substitution on the incorporation of tyrosine into the melanin of mouse skin. Archives of Biochemistry and Biophysics 96, 562–568.CrossRefGoogle ScholarPubMed
Falconer, D. S. & Isaacson, J. H. (1959). Adipose, a new inherited obesity of the mouse. Journal of Heredity 50, 290–292.CrossRefGoogle Scholar
Feinstein, R. N., Howard, J. B., Braun, J. T. & Russell, W. L. (1964). Acatalasemic mice. Proceedings of the National Academy of Science, U.S.A. 52, 661–662.CrossRefGoogle ScholarPubMed
Feinstein, R. N., Howard, J. B., Braun, J. T. & Seaholm, J. E. (1966). Acatalasemic and hypocatalasemic mouse mutants. Genetics 53, 923–933.CrossRefGoogle ScholarPubMed
Freid, G. H. & Antopol, W. (1966). Enzymatic activities in tissues of obese-hyperglycemic mice. American Journal of Physiology 211, 1321–1324.CrossRefGoogle Scholar
Goodman, D. S., Deykin, D. & Shiratori, T. (1962). The formation of cholesterol esters with rat liver enzymes. The Journal of Biological Chemistry 239, 1335–1345.CrossRefGoogle Scholar
Haessler, H. A. & Crawford, J. D. (1965). Alteration in the fatty acid composition of depot fat associated with obesity. Annals of the New York Academy of Science 131, part I, 476–484.CrossRefGoogle ScholarPubMed
Harris, H. (1970). The Principles of Human Biochemical Genetics, pp. 174–175. London: North Holland.Google Scholar
Jansen, G. R., Zanetti, M. E. & Hutchison, C. F. (1967). Studies on lipogenesis in vivo. Fatty acid and cholesterol synthesis in hyperglycemic-obese mice. Biochemical Journal 102, 870–877.CrossRefGoogle Scholar
Kacser, H. & Burns, J. (1968). Causality, complexity and computers. In Quantitative Biology of Metabolism. 3rd International Symposium, Biologicshe Anstalt Helgoland, pp. 11–23.CrossRefGoogle Scholar
Kacser, H. & Burns, J. (1972). Control of flux. Society for Experimental Biology 27 (in the Press).Google Scholar
Kornaker, M. S. & Lowenstein, J. (1964 a). Citrate cleavage enzyme in liver of obese and non-obese mice. Science 144, 1027–1028.CrossRefGoogle Scholar
Kornaker, M. S. & Lowenstein, J. M. (1964 b). Citrate and the conversion carbohydrate into fat. A comparison of citrate and acetate incorporation into fatty acids. Biochemical Journal 93, 378–388.Google Scholar
Kornaker, M. A. & Lowenstein, J. M. (1965 a). Citrate and the conversion of carrbohydrate into fat. The activities of citrate-cleavage enzyme and acetate thiokinase in livers of starved and refed rats. Biochemical Journal 94, 209–215.CrossRefGoogle Scholar
Kornaker, M. S. & Lowenstein, J. M. (1965 b). Citrate and the conversion of carrbohydrate into fat. The activities of citrate-cleavage enzyme and acetate thiokinase in livers of normal and diabetic rats. Biochemical Journal 95, 832–837.CrossRefGoogle Scholar
Kornberg, A. (1955). Lactic dehydrogenase from muscle. Methods in Enzymology 1, 441–444.CrossRefGoogle Scholar
Lochaya, S., Hamilton, J. C. & Mayer, J. (1963). Lipase and glycerokinase activities in the adipose tissue of obese-hyperglycemic mice. Nature 197, 182–183.CrossRefGoogle Scholar
Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randle, R. J. (1951). Protein measurement with Folin–Wu phenol reagent. Journal of Biological Chemistry 193, 265–275.CrossRefGoogle Scholar
Lynen, F., Matsuhashi, M., Numa, S. & Schweizer, E. (1964). The cellular control of fatty acid synthesis at the enzymatic level. Biochemical Society Symposium 24, 43–56.Google Scholar
Marshall, N. B., Barnett, R. G. & Mayer, J. (1954). Hypothalmic lesions in goldthioglucose injected mice. Proceedings of the Society of Experimental Biology and Medicine 90, 240–244.CrossRefGoogle Scholar
Mayer, J. (1960). The obese-hyperglycemic syndrome of mice as an example of ‘metabolic’ obesity. American Journal of Clinical Nutrition 8, 712–718.CrossRefGoogle Scholar
Mayer, J. & Thomas, D. W. (1967). Regulation of food intake and obesity. Science, 156, 328–337.CrossRefGoogle ScholarPubMed
Ochoa, S. (1955 a). Isocitric dehydrogenase system (t.p.n.) of pig heart. Methods in Enzymology 1, 699–705.CrossRefGoogle Scholar
Ochoa, S. (1955 b). Malic dehydrogenase from pig heart. Methods in Enzymology 1, 735–739.CrossRefGoogle Scholar
Ochoa, S. (1955 c). ‘Malic’ enzyme. Methods in Enzymology 1, 739–753.CrossRefGoogle Scholar
Racker, E. (1950). Speetrophotometric measurements of the enzymatic formation of fumaric and cis-aconitic acids. Biochimica et biophysica acta 4, 212–214.CrossRefGoogle Scholar
Russell, L. B. (1971). Definition of functional units in a small chromosomal segment of the mouse and its use in interpreting the nature of radiation–induced mutations. Mutation Research 11, 107–123.CrossRefGoogle Scholar
Schreeve, W. H., Lamdin, E., Oji, N. & Slavinski, R. (1967). Biosynthesis of fatty acids in obese mice in vivo. 1. Studies with glucose-1-3H(1-14C), glucose-6-3H(6-14C), dl-lactate-2-3H (2-14C) and glycerol-2-3H(1,3-14C). Biochemistry 6, 1160–1167.CrossRefGoogle Scholar
Seidman, I., Horland, A. A. & Teebor, G. W. (1967). Hepatic glycolytic and gluconeogenic enzymes of the obese-hyperglycemic mouse. Biochimica et biophysica acta 146, 600–603.CrossRefGoogle ScholarPubMed
Spencer, A. F. & Lowenstein, J. M. (1966). Citrate and the conversion of carrbohydrate into fat. Citrate cleavage in obesity and lactation. Biochemical Journal 99, 760–765.CrossRefGoogle ScholarPubMed
Srere, P. A. (1959). The citrate cleavage enzyme. II. Stoichiometry, substrate specificity and its use for coenzyme A assay. Journal of Biological Chemistry 236, 50–53.CrossRefGoogle Scholar
Stein, J., Anderson, J. & Hollifield, G. (1967). Selective mobilisation of fatty acids from the adipose tissue of the obese hyperglycemic mice. Metabolism 16, 658–762.CrossRefGoogle Scholar
Treble, D. H. & Mayer, J. (1963). Glycerolkinase activity in white adipose tissue of obese-hyperglycemic mouse. Nature 200, 363–364.CrossRefGoogle Scholar
Umbarger, H. E. (1961). Feedback control by end product inhibition. Cold Spring Harror Symposia of Quantitative Biology 26, 301–312.CrossRefGoogle Scholar
Van der Kroon, P. H. W. & Buis, A. J. M. (1970). Linkage of dwarf and obese in the mouse. Genetica 41, 57–60.CrossRefGoogle ScholarPubMed
Weber, G., Stamm, N. B. & Fisher, E. A. (1965). Insulin: inducer of pyruvate kinase. Science 147, 65–67.CrossRefGoogle Scholar
Wise, E. M. & Ball, E. G. (1964). Malic enzyme and lipogenesis. Proceedings of the National Academy of Science, U.S.A. 52, 1255–1263.CrossRefGoogle ScholarPubMed
Yen, T. T. T., Lowry, L. & Steinmitz, J. (1968). Obese locus in Mus musculus: a gene dosage effect. Biochemical and Biophysical Research Communications 33, 883–887.CrossRefGoogle ScholarPubMed