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Biochemical Genetics

, Volume 4, Issue 1, pp 105–125 | Cite as

Genetic control of enzyme activity in higher organisms

  • James B. Wyngaarden
Proceedings of the symposium genetic control of mammalian metabolism held at The Jockson Laboratory, Bar Harbor, Maine

Abstract

The known intracellular controls of metabolism in higher organisms include regulation of transcription and translation, of enzyme turnover, and of enzyme activity. The magnitudes of changes of enzyme activity attributable to enzyme induction or catabolism in mammalian cells are small compared with those commonly observed during induction or repression in bacteria. Nevertheless, changes of five- to twenty-fold in activity in response to dietary changes or drug administration clearly are of metabolic significance, as, for example, in regulation of hepatic gluconeogenesis. Feedback controls provide a more versatile form of fast response for metabolic adaptations in cells of higher organisms and allowing tailoring of metabolism to exhaust or conserve different substrates intracellularly.

Keywords

Enzyme Activity Mammalian Cell Drug Administration Feedback Control Genetic Control 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Allfrey, V. G. (1968). Some observations on histone acetylation and its temporal relationship to gene activation. In San Pietro, A., Lamborg, M. R., and Kenney, F. T. (eds.), Regulatory Mechanisms for Protein Synthesis in Mammalian Cells, Academic Press, New York, pp. 65–100.Google Scholar
  2. Alpers, D. H., and Tomkins, G. (1966). Sequential transcription of the genes of the lactose operon and its regulation by protein synthesis. J. Biol. Chem. 241 4434.Google Scholar
  3. Ames, B. N., and Hartman, P. E. (1963). The histidine operon. Cold Spring Harbor Symp. Quant. Biol. 28 349.Google Scholar
  4. Attardi, G., Parnas, H., Hwang, M., and Attardi, M. (1966). Giant size rapidly labeled nuclear RNA and cytoplasmic messenger RNA in immature duck erythrocytes. J. Mol. Biol. 20 145.Google Scholar
  5. Barberich, M. A., Venatianer, P., and Goldberger, R. F. (1966). Alternative modes of derepression of the histidine operon observed in Salmonella typhimurium. J. Biol. Chem. 241 4426.Google Scholar
  6. Beutler, E. (1966). Glucose 6-phosphate dehydrogenase deficiency. In Stanbury, J. B., Wyngaarden, J. B., and Fredrickson, D. S. (eds.), The Metabolic Basis of Inherited Disease, 2nd ed., McGraw-Hill, New York, pp. 1060–1089.Google Scholar
  7. Britten, R. J., and Kohne, D. E. (1967). Nucleotide sequence repetition in DNA. In Yearbook of the Carnegie Institute (1965–66), p. 78.Google Scholar
  8. Caskey, C. T., Ashton, D. M., and Wyngaarden, J. B. (1964). The enzymology of feedback inhibition of glutamine phosphoribosylpyrophosphate amidotransferase by purine ribonucleotides. J. Biol. Chem. 239 2570.Google Scholar
  9. Englesberg, E., Squires, C., and Merank, F. Jr. (1969). The l-arabinose operon in Escherichia coli B/r: A genetic demonstration of two functional states of the product of a regulator gene. Proc. Natl. Acad. Sci. 62 1100.Google Scholar
  10. Ganschow, R., and Schimke, R. T. (1968). Genetic control of catalase in inbred mice. In San Pietro, A., Lamborg, M. R., and Kenney, F. T. (eds.), Regulatory Mechanisms for Protein Synthesis in Mammal Cells, Academic Press, New York, pp. 377–397.Google Scholar
  11. Garren, L. D., Howell, R. R., Tomkins, G. M., and Crocco, R. M. (1964). A paradoxical effect of actinomycin D: The mechanism of regulation of enzyme synthesis by hydrocortisone. Proc. Natl. Acad. Sci. 52 1121.Google Scholar
  12. Georgiev, G. P. (1968). The regulation of the biosynthesis and transport of messenger RNA in animal cells. In San Pietro, A., Lamborg, M. R., and Kenney, F. T. (eds.), Regulatory Mechanisms for Protein Synthesis in Mammalian Cells, Academic Press, New York, pp. 25–48.Google Scholar
  13. Gilbert, W., and Müller-Hill, B. (1966). Isolation of the lac repressor. Proc. Natl. Acad. Sci. 56 1891.Google Scholar
  14. Gilbert, W., and Müller-Hill, B. (1967). The lac operator is DNA. Proc. Natl. Acad. Sci. 58 2415.Google Scholar
  15. Henderson, J. F., Caldwell, I. C., and Paterson, A. R. P. (1967). Decreased feedback inhibition in a 6-methylmercaptopurine ribonucleoside resistant tumor. Cancer Res. 27 1773.Google Scholar
  16. Henderson, J. F., Rosenbloom, F. M., Kelley, W. N., and Seegmiller, J. E. (1968). Variations in purine metabolism of cultured skin fibroblasts from patients with gout. J. Clin. Invest. 47 1511.Google Scholar
  17. Imamoto, F., Mirokawa, N., Sato, K., Mishima, S., Nishimura, T., and Matsushiro, A. (1965). On the transcription of the tryptophan operon in Escherichia coli. II. J. Mol. Biol. 13 157.Google Scholar
  18. Jacob, F., and Monod, J. (1961). Genetic regulatory mechanisms in the synthesis of proteins. J. Mol. Biol. 3 318.Google Scholar
  19. Jost, J. P., Khairallah, E., and Pitot, H. C. (1968). Studies on the induction and repression of enzymes in rat liver. V. Regulation of the rate of synthesis and degradation of serine dehydratase by dietary amino acids and glucose. J. Biol. Chem. 243 3057.Google Scholar
  20. Kenney, F. T., Reel, J. R., Hager, C. B., and Wittliff, J. L. (1968). Hormonal induction and repression. In San Pietro, A., Lamborg, M. R., and Kenney, F. T. (eds.), Regulatory Mechanisms for Protein Synthesis in Mammalian Cells, Academic Press, New York, pp. 119–142.Google Scholar
  21. Knox, W. E., and Auerbach, V. H. (1955). The hormonal control of tryptophan peroxidase in the rat. J. Biol. Chem. 214 307.Google Scholar
  22. Langan, T. A. (1968). Histone phosphorylation: Stimulation by adenosine 3′,5′-monophosphate. Science 162 579.Google Scholar
  23. Lin, E. C. C., and Knox, W. E. (1957). Adaptation of the rat liver tyrosine-α-ketoglutarate transaminase. Biochim. Biophys. Acta 26 85.Google Scholar
  24. Malamy, M. H. (1966). Frameshift mutations in the lactose operon of E. coli. Cold Spring Harbor Symp. Quant. Biol. 31 189.Google Scholar
  25. Martin, D., Jr., Tomkins, G. M., and Granner, D. (1969). Synthesis and induction of tyrosine amino-transferase in synchronized hepatoma cells in culture. Proc. Natl. Acad. Sci. 62 248.Google Scholar
  26. Martin, R. G., Silbert, D. F., Smith, D. W. E., and Whitfield, H. J., Jr. (1966). Polarity in the histidine operon. J. Mol. Biol. 21 357.Google Scholar
  27. Monod, J., Changeux, J.-P., and Jacob, F. (1963). Allosteric protein and cellular control systems. J. Mol. Biol. 6 306.Google Scholar
  28. Monod, J., Wyman, J., and Changeux, J.-P. (1965). On the nature of allosteric transitions: A plausible model. J. Mol. Biol. 12 88.Google Scholar
  29. Moyed, H. S. (1960). False feedback inhibition: Inhibition of tryptophan biosynthesis by 5-methyl tryptophan. J. Biol. Chem. 235 1098.Google Scholar
  30. Moyed, H. S. (1961). Interference with feedback control of enzyme activity. Cold Spring Harbor Symp. Quant. Biol. 26 323.Google Scholar
  31. Naughton, M. A., and Dintzis, H. M. (1962). Sequential biosynthesis of the peptide chains of hemoglobin. Proc. Natl. Acad. Sci. 48 1822.Google Scholar
  32. Newton, W. A., Beckwith, J. R., Zipser, D., and Brenner, S. (1965). Nonsense mutants and polarity in the lac operon of E. coli. J. mol. Biol. 14 290.Google Scholar
  33. Paglia, A. E., Valentine, W. N., Baughan, M. A., Miller, D. R., Reed, C. F., and McIntyre, O. R. (1968). An inherited molecular lesion of erythrocyte pyruvate kinase. Identification of a kinetically aberrant isozyme associated with premature hemolysis. J. Clin. Invest. 47 1929.Google Scholar
  34. Parker, W. C., and Bearn, A. G. (1963). Application of genetic regulatory mechanisms to human genetics. Am. J. Med. 34 680.Google Scholar
  35. Peraino, C., Blake, R. L., and Pitot, H. C. (1965). Studies on the induction and repression of enzymes in rat liver. III. Induction of ornithine δ-transaminase and threonine dehydrase by oral intubation of free amino acids. J. Biol. Chem. 240 3039.Google Scholar
  36. Peterkofsky, B., and Tomkins, G. M. (1967). Effect of inhibitors of nucleic acid synthesis on steroid-mediated induction of tyrosine aminotransferase in hepatoma cell cultures. J. Mol. Biol. 30 49.Google Scholar
  37. Peterkofsky, B., and Tomkins, G. M. (1968). Evidence for the steroid-induced accumulation of tyrosine-aminotransferase messenger RNA in the absence of protein synthesis. Proc. Natl. Acad. Sci. 60 222.Google Scholar
  38. Ptashne, M. (1967). Isolation of the λ-phage repressor. Proc. Natl. Acad. Sci. 57 306.Google Scholar
  39. Rowe, P. B., and Wyngaarden, J. B. (1966). The mechanism of dietary alterations in rat hepatic xanthine oxidase levels. J. Biol. Chem. 241 5571.Google Scholar
  40. Rowe, P. B., and Wyngaarden, J. B. (1968). Glutamine phosphoribosylpyrophosphate amidotransferase. Purification, substructure, amino acid composition, and absorption spectra. J. Biol. Chem. 243 6373.Google Scholar
  41. Rowe, P. B., and Wyngaarden, J. B. (1969). Dietary nitrogen levels and purine catabolic enzymes in rat liver. (Submitted for publication.)Google Scholar
  42. Rowe, P. B., Coleman, M. D., and Wyngaarden, J. B. (1969). Glutamine phosphoribosylpyrophosphate amidotransferase. Catalytic and conformational heterogeneity of the pigeon liver enzyme. Biochemistry (In press).Google Scholar
  43. Samarina, O. P., Lukanidin, E. M., Molnar, J., and Georgiev, G. P. (1968). Structural organization of nuclear complex containing DNA-like RNA. J. Mol. Biol. 33 251.Google Scholar
  44. Schimke, R. T. (1962). Differential effects of fasting and of protein-free diets on levels of urea cycle enzymes in rat liver. J. Biol. Chem. 237 1921.Google Scholar
  45. Schimke, R. T. (1964). The importance of both synthesis and degradation in the control of arginase levels in rat liver. J. Biol. Chem. 239 3803Google Scholar
  46. Schimke, R. T., Sweeney, E. W., and Berlin, C. M. (1964). An analysis of the kinetics of rat liver tryptophan pyrrolase induction: The significance of both enzyme synthesis and degradation. Biochem. Biophys. Res. Commun. 15(3): 214.Google Scholar
  47. Schimke, R. T., Sweeney, E. W., and Berlin, C. M. (1965). The roles of synthesis and degradation in the control of rat liver tryptophan pyrrolase. J. Biol. Chem. 240 322.Google Scholar
  48. Segal, H. L., and Kim, Y. S. (1965). Environmental control of enzyme synthesis and degradation. J. Cell. Comp. Physiol. 66 (No. 2, Pt. II): 11.Google Scholar
  49. Sheppard, D., and Englesberg, E. (1966). Positive control in the l-arabinose gene-enzyme complex of Escherichia coli B/r as exhibited with stable merodiploids. Cold Spring Harbor Symp. Quant. Biol. 31 345.Google Scholar
  50. Smith, L. H., Jr., Hugeley, C. M., Jr., and Bain, J. A. (1966). Hereditary orotic aciduria. In Stanbury, J. B., Wyngaarden, J. B., and Fredrickson, D. S. (eds.), The Metabolic Basic of Inherited Disease, 2nd ed., McGraw-Hill, New York, pp. 739–758.Google Scholar
  51. Spelsberg, T. C., Tankersley, S., and Hnilica, L. S. (1969). The interaction of RNA polymerase with histones. Proc. Natl. Acad. Sci. 62 1218.Google Scholar
  52. Stent, G. S. (1964). The operon: On its third anniversary. Science 144 816.Google Scholar
  53. Thompson, E. B., Tomkins, G. M., and Curran, J. E. (1966). Induction of tyrosine α-ketoglutarate transaminase by steroid hormones in a newly established tissue culture cell line. Proc. Natl. Acad. Sci. 56 296.Google Scholar
  54. Tomkins, G. M. (1968). Enzyme induction in tissue culture. In San Pietro, A., Lamborg, M. R., and Kenney, F. T. (eds.), Regulatory Mechanisms for Protein Synthesis in Mammalian Cells, Academic Press, New York, pp. 269–282.Google Scholar
  55. Tomkins, G. M., and Ames, B. N. (1967). The operon concept in bacteria and in higher organisms. Natl. Cancer Inst. Monograph No. 27, pp. 221–234.Google Scholar
  56. Tomkins, G. M., Garren, L. D., Howell, R. R., and Peterkofsky, B. (1965). The regulation of enzyme synthesis by steroid hormones: The role of translation. J. Cell. Comp. Physiol. 66 (No. 2, Pt. II): 137.Google Scholar
  57. Tomkins, G. M., Thompson, E. B., Hayashi, S., Gelehrter, T., Granner, D., and Peterkofsky, B. (1966). Tyrosine transaminase induction in mammalian cells in tissue culture. Cold Spring Harbor Symp. Quant. Biol. 31 349.Google Scholar
  58. Tomkins, G. M., Gelehrter, T. D., Granner, D. K., Peterkofsky, B., and Thompson, E. B. (1968). Regulation of gene suppression in mammalian cells. In Exploitable Molecular Mechanisms and Neophasia, Williams & Wilkins Co., Baltimore, pp. 229–251.Google Scholar
  59. Whitfield, J. J., Jr., Martin, R. G., and Ames, B. N. (1966). Classification of aminotransferase (C gene) mutants in the histidine operon. J. Mol. Biol. 21 335.Google Scholar
  60. Wyngaarden, J. B., Appel, S. H., and Rowe, P. B. (1968). Control of biosynthetic pathways by regulatory enzymes. In Exploitable Molecular Mechanisms and Neoplasia, Williams & Wilkins Co., Baltimore, pp. 415–434.Google Scholar
  61. Yanofsky, C., and Ito, J. (1966). Nonsense codons and polarity in the tryptophan operon. J. Mol. Biol. 21 313.Google Scholar

Copyright information

© Plenum Publishing Corporation 1970

Authors and Affiliations

  • James B. Wyngaarden
    • 1
  1. 1.Duke University Medical CenterDurham

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