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Molecular biology of zinc

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Biotechnology for Solving Agricultural Problems

Part of the book series: Beltsville Symposia in Agricultural Research ((BSAR,volume 10))

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Abstract

The ubiquitous distribution of zinc (Zn) in microbial, plant and animal cells suggests a wide range of potential functions for this transition element. The physiological role of Zn has centered on its interaction with enzymes. For example, the cessation of growth associated with nutritional Zn deficiency involves a reduction in DNA polymerase activity and concomitant reduction in DNA synthesis. Similarly, RNA polymerases I, II, and III are all Zn metalloenzymes and in appropriate model systems a reduction in the synthesis r-RNA, mRNA and t-RNA, respectively, is observed with cellular Zn depletion. The effect of Zn at the genetic level is most dramatically shown through induction of metallothionein synthesis. This protein influences the kinetics of Zn uptake by cells. It has been clearly demonstrated that metallothionein synthesis is under transcriptional control. Zinc and glucocorticoids, as well as glucagon and epinephrine (via elevation of cellular cAMP levels) all induce transcription of the metallothionein gene. Recently it has been shown that a 12 by fragment of the metallothionein gene promoter sequence regulates expression of heterologous genes in vivo, which demonstrates that Zn can have a direct effect on expression of specific genes. These results illustrate the potential of this relatively nontoxic metal in biotechnology applications where Zn responsive fusion genes could be utilized.

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References

  • Alfaro, B. and F. Heaton. 1974. The subcellular distribution of copper, zinc, and iron in liver and kidney. Changes during copper dificiency in the rat. Br. J. Nutr. 32:435–445.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, R. D., B. W. Birren, T. Gans, J. E. Piletz and H. R. Herschman. 1983. Molecular cloning of the rat methallothionein-I (MT-1) mRNA sequence. DNA 2:15–22.

    Article  Google Scholar 

  • Auld, D. S., H. Kawaguhi, D. M. Livingson and B. L. Vallee. 1974. RNA-dependent DNA polymerase (reverse transcriptase) from avian myeloblastosis virus: a zinc metalloenzyme. Proc. Nat. Acad. Sci. 71:2091–2095.

    Article  PubMed  CAS  Google Scholar 

  • Brady, F. O. and B. Helvig. 1984. Effect of epinephrine and norepinephrine on zinc thionein levels and induction in rat liver. Amer. J. Physiol. 247:E318–E322.

    PubMed  CAS  Google Scholar 

  • Bryan, S. E., D. L. Vizard, D. A. Beary, R. A. LaBiche and K. J. Hardy. 1981. Partitioning of zinc and copper within subnuclear nucleoprotein particles. Nucl. Acids Res. 9:5811–5821.

    Article  PubMed  CAS  Google Scholar 

  • Butt, T. R., E. J. Sternberg, J. A. Gorman, P. Clark, D. Hamer, M. Rosenberg and S. T. Crooke. 1984. Copper metallothionein of yeast, structure of the gene, and regulation of expression. Proc. Nat. Acad. Sci. 81:3332–3336.

    Article  PubMed  CAS  Google Scholar 

  • Carter, A. D., B. K. Felder, M. T. Walling, M. F. Jubier, C. J. Schmidt and D. H. Hamer. 1984. Duplicated heavy metal control sequences of the mouse metallothionein-I gene. Proc. Nat. Acad. Sci. 81:7392–7396.

    Article  PubMed  CAS  Google Scholar 

  • Chesters, J. K. 1972. The role of zinc ions in the transformation of lymphocytes by phytohaemagglutinin. Biochem. J. 130:133–319.

    PubMed  CAS  Google Scholar 

  • Coppen, D. E., R. J. Cousins and D. E. Richardson. 1985. Effect of zinc on chemically induced peroxidation in rat liver parenchymal cells in primary culture. Fed. Proc. 44:6404.

    Google Scholar 

  • Cousins, R. J. 1985. Absorption, transport, and intracellular metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin. Physiol. Rev. 65:238–309.

    PubMed  CAS  Google Scholar 

  • Cousins, R. J. and A. R. Burges. 1984. Influence of glucagon and epinephrine on metallothionein induction and zinc exchange in rat liver parenchymal cells. Fed. Proc. 44:3403.

    Google Scholar 

  • DiSilvestro, R. A. and R. J. Cousins. 1984. Mediation of endotoxin-induced changes in zinc metabolism in rats. Amer. J. Physiol; 247:E436–E441.

    PubMed  CAS  Google Scholar 

  • DiSilvestro, R. A. and R. J. Cousins. 1984. Glucocorticoid independent mediation of interleukin-1 induced changes in serum zinc and liver metallothionein levels. Life Sci. 35:2113–2118.

    Article  PubMed  CAS  Google Scholar 

  • Durnam, D. M., F. Perrin, F. Gannon and R. D. Palmiter. 1980. Isolation and characterization of the mouse metallothionein-I gene. Proc. Nat. Acad. Sci. USA 77:6511–6515.

    Article  PubMed  CAS  Google Scholar 

  • Eichhorn, G. L. 1973. Pp. 1191–1243 in Inorganic Biochemistry. Elsevier Scientific Publishing Co., New York.

    Google Scholar 

  • Etzel, K. R., S. G. Shapiro and R. J. Cousins. 1979. Regulation of liver metallothionein and plasma zinc by the glucocorticoid dexamethasone. Biochem. Biophys. Res. Comm. 89:1120–1126.

    Article  PubMed  CAS  Google Scholar 

  • Etzel, K. R., M. R. Swerdel, J. N. Swerdel and R. J. Cousins. 1982. Endotoxin-induced changes in copper and zinc metabolism in the syrian hamster. J. Nutr. 112:2363–2373.

    PubMed  CAS  Google Scholar 

  • Failla, M. L. and R. J. Cousins. 1978. Zinc uptake by isolated rat liver parenchymal cells. Biochem. Biophys. Acta 538:434–444.

    Google Scholar 

  • Falchuk, K. H., A. Krishan and B. L. Vallee. 1975. DNA distribution in the cell cycle of Euglena gracilis, cytofluorometry of zinc deficient cells. Biochemistry 14:3439–3444.

    Article  PubMed  CAS  Google Scholar 

  • Falchuk, K. H., B. Mazus, L. Ulpino and B. L. Vallee. 1976. Euglena gracilis DNA dependent RNA polymerase II: a zinc metalloenzyme. Biochemistry 15:4468–4475.

    Article  PubMed  CAS  Google Scholar 

  • Falchuk, K. H., L. Ulpino, B. Maxus and B. L. Vallee. 1977. E. Gracilis RNA polymerase I: a zinc metalloenzyme. Biochem. Biophys. Res. Comm. 74:1206–1212.

    Article  PubMed  CAS  Google Scholar 

  • Fazakerly, G. V. 1984. Zinc Z-DNA. Nucl. Acids Res. 12:3643–3648.

    Article  Google Scholar 

  • Ferrin, L. J., A. S. Mildvan and L. A. Leob. 1983. Metal content of DNA polymerase I purified from overproducing and wild type Escherichia coli. Biochem. Biophys. Res. Comm. 112:723–727.

    Article  PubMed  CAS  Google Scholar 

  • Fosmire, G. J., Y. Y. Al-Ubaidi, E. Halas and H. H. Sandstead. 1974. The effect of zinc deprivation on the brain. Adv. Expl. Med. Biol. 48:329–345.

    CAS  Google Scholar 

  • Hamer, D. H. and M. Walling. 1982. Regulation in vivo of a cloned mammalian gene: cadmium induces the transcription of a mouse metallothionein gene in SV 40 vectors. J. Mol. Appl. Genet. 1:273–288.

    PubMed  CAS  Google Scholar 

  • Karin, M. and R. I. Richards. 1982. Human metallothionein genes — primary structure of the metallothionein-II gene and a related processed gene. Nature (London) 299:797–802.

    Article  CAS  Google Scholar 

  • Kreutzfeld, K. L., K. Y. Lei, M. D. Bergman and F. L. Meyskens, Jr. 1985. Dexamethasone and zinc in combination inhibit the anchorage-independent growth of S-91 cloudman murine melanoma. Life Sci. 36:823–827.

    Article  PubMed  CAS  Google Scholar 

  • Li, T. Y., A. J. Kramer, C. F. Shaw III and D. H. Petering. 1980. Ligand substitution reactions of metallothionein with EDTA and apo-carbonic anhydrase. Proc. Nat. Acad. Sci. USA 77:6334–6338.

    Article  PubMed  CAS  Google Scholar 

  • Lieberman, I., R. Abrams, N. Hun and P. Ove. 1963. Levels of enzyme activity and deoxyribonucleic acid synthesis in mammalian cells cultured from the animal. J. Biol. Chem. 238:3935–3962.

    Google Scholar 

  • Macapinlac, M. P., W. N. Pearson, G. H. Barney and W. J. Darby. 1968. Protein and nucleic acid metabolism in the testes of zinc-deficient rats. Nutrition 95:569–577.

    CAS  Google Scholar 

  • Mazus, B., K. H. Falchuk and B. L. Vallee. 1984. Histone formation, gene expression, and zinc deficiency in Euglena gracilis. Biochemistry 23:43–47.

    Article  Google Scholar 

  • O’Neal, R. M., G. W. Pla, M. R. S. Fox, F. S. Gibson and B. E. Fry, Jr. 1970. Effect of zinc deficiency and restricted feeding on protein and ribonucleic acid metabolism of rat brain. J. Nutr. 100:491–497.

    PubMed  Google Scholar 

  • Palmiter, R. D., H. Y. Chen and R. D. L. Brinster. 1982a. Differential regulation of metallothionein-thymidine kinase fusion genes in transgenic mice and their offspring. Cell 29:701–710.

    Article  PubMed  CAS  Google Scholar 

  • Palmiter, R. D., R. L. Brinster, R. E. Hamer, M. E. Trumkbauer, M. G. Rosenfeld, N. C. Birnberg and R. M. Evans. 1982b. Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature 300:611–615.

    Article  PubMed  CAS  Google Scholar 

  • Pattison, S. E. and R. J. Cousins. 1985. Zinc transport and metabolism by hepatocytes. Fed. Proc. 44 (in press).

    Google Scholar 

  • Petranyi, P., J. J. Jendrisak and R. R. Burgess. 1977. RNA polymerase II from wheat germ contains tightly bound zinc. Biochem. Biophys. Res. Comm. 74:1031–1038.

    Article  PubMed  CAS  Google Scholar 

  • Prasad, A. S., D. Oberleas, D. Koniuch and E. DuMouchelle. 1973. Ribonuclease and deoxyribonuclease activities in zinc-deficient tissues. J. Lab. Clin. Med. 82:461–466.

    PubMed  CAS  Google Scholar 

  • Prasad, A. S. and D. Oberleas. 1974. Thymidine kinase activity and incorporation of thymidine into DNA in zinc-deficient tissue. J. Lab. Chin. Med. 83:634.

    CAS  Google Scholar 

  • Prasad, A. S., P. Rabbani, A. Abbasil, E. Bowersox and M. R. S. Fox. 1978. Experimental zinc deficiency in humans. Ann. Intern. Med. 89:483–490.

    PubMed  CAS  Google Scholar 

  • Price, C. A. and B. L. Vallee. 1962. Euglena gracilus, a test organism for study of zinc. Plant Physiol. 37:428–433.

    Article  PubMed  CAS  Google Scholar 

  • Quinones, S. R. and R. J. Cousins. 1984. Augmentation of dexamethasone induction of rat liver metallothionein by zinc. Biochem. J. 219:959–963.

    PubMed  CAS  Google Scholar 

  • Raulin, J. 1969. Etudes cliniques sur la vegetation. Ann. Sci. Nat. Bot. Biol. Vegetale 11:93–299.

    Google Scholar 

  • Richards, M. P. and R. J. Cousins. 1975. Mammalian zinc homeostasis: requirements for RNA and metallothionein synthesis. Biochem. Biophys. Res. Comm. 64:1215–1223.

    Article  PubMed  CAS  Google Scholar 

  • Richards, M. P. and R. J. Cousins. 1976a. Metallothionein and its relationship to the metabolism of dietary zinc in rats. J. Nutr. 106:1591–1599.

    PubMed  CAS  Google Scholar 

  • Richards, M. P. and R. J. Cousins. 1976b. Zinc-binding protein: relationship to short term changes in zinc metabolism. Proc. Soc. Expl. Biol. Med. 153:52–56.

    CAS  Google Scholar 

  • Rubin, H. 1972. Inhibition of DNA synthesis in animal cells by ethylene diamine tetraacetate, and its reversal of zinc. Proc. Nat. Acad. Sci. 69:712–716.

    Article  PubMed  CAS  Google Scholar 

  • Sandstead, H. H. and R. A. Rinaldi. 1969. Impairment of deoxyribonucleic acid synthesis by dietary zinc deficiency in the rat. J. Cell Physiol. 73:81–84.

    Article  PubMed  CAS  Google Scholar 

  • Sandstead, H. H., M. Terhune, R. N. Brady, D. Gillespie and W. L. Holloway. 1971. Zinc deficiency: brain DNA protein and lipids; and liver ribosomes and RNA polymerase. Clin. Res. 19:83–89.

    Google Scholar 

  • Schneider, E. and C. A. Price. 1962. Decreased ribonucleic acid levels: a possible cause of growth inhibition in zinc deficiency. Biochem. Biophys. Acta 55:406–410.

    Article  PubMed  CAS  Google Scholar 

  • Scrutton, M. C., C. W. Wu and D. A. Goldthwait. 1971. The presence and possible role of zinc in RNA polymerase obtained from Escherichia coli. Proc. Nat. Acad. Sci. 68:2497–2501.

    Article  PubMed  CAS  Google Scholar 

  • Shapiro, S. G. and R. J. Cousins. 1980. Induction of rat liver metallothionein mRNA and its distribution between free and membrane-bound polysomes. Biochem. J. 190:755–764.

    PubMed  CAS  Google Scholar 

  • Shapiro, S. G., K. S. Aquibb, LK. A. Markowitz and R. J. Cousins. 1978. Cell-free synthesis of metallothionein directed by rat liver polyadenylated messenger RNA. Biochem. J. 175:833–840.

    PubMed  CAS  Google Scholar 

  • Slaby, I., B. Kind and A. Holmgren. 1984. T7 DNA polymerase is not a zinc-metalloenzyme and the polymerase and exonuclease activities are inhibited by zinc ions. Biochem. Biophys. Res. Commun. 122:1410–1417.

    Article  PubMed  CAS  Google Scholar 

  • Slater, J. P., A. S. Mildvan and L. A. Loeb. 1971. Zinc in DNA polymerase. Biochem. Biophys. Res. Commun. 44:37–43.

    Article  PubMed  CAS  Google Scholar 

  • Smeyers-Verbeke, J., C. May, P. Drochmans and D. L. Massart. 1977. The determination of Cu, Zn, and Mn in subcellular rat liver fractions. Anal. Biochem. 83:746–753.

    Article  PubMed  CAS  Google Scholar 

  • Somers, M. and E. J. Underwood. 1969. Ribonuclease activity and nucleic acid and protein metabolism in the testes of zinc-deficient rats. Austral. J. Biol. Sci. 22:1277–1282.

    CAS  Google Scholar 

  • Springgate, C. F., A. S. Mildvan, R. Abramson, J. L. Engle and L. A. Leob. 1973. Escherichia coli deoxyribonucleic acid polymerase I, a zinc metalloenzyme. J. Biol. Chem. 248:5987–5993.

    PubMed  CAS  Google Scholar 

  • Squibb, K. S. and R. J. Cousins. 1974. Control of cadmium binding protein synthesis in rat liver. Environ. Physiol. Biochem. 4:24–30.

    PubMed  CAS  Google Scholar 

  • Squibb, K. S., R. J. Cousins and S. L. Feldman. 1977. Control of zinc-thionein synthesis in rat liver. Biochem. J. 164:223–228.

    PubMed  CAS  Google Scholar 

  • Stuart, G. W., P. F. Searle, H. Y. Chen, R. L. Brinster and R. D. Palmiter. 1984. A 12-base-pair DNA motif that is repeated several times in metallothionein gene promoters confers metal regulation to a heterologous gene. Proc. Nat. Acad. Sci. 81:7318–7322.

    Article  PubMed  CAS  Google Scholar 

  • Swenerton, H., R. Shrader and L. S. Hurley. 1969. Zinc-deficient embryos: reduced thymidine incorporation. Science 166:1014–1015.

    Article  PubMed  CAS  Google Scholar 

  • Tal, M. 1969. Metal ions and ribosomal conformation. Biochim. Biophys. Acta 195:76–80.

    PubMed  CAS  Google Scholar 

  • Terhune, M. W. and H. H. Sandstead. 1972. Decreased RNA polymerase activity in mammalian zinc deficiency. Science 177:68–69.

    Article  PubMed  CAS  Google Scholar 

  • Thornalley, P. J. and M. Vasak. 1985. Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanisms of its reaction with superoxide and hydroxyl radical. Biochim. Biophys. Acta 827:36–44.

    Article  PubMed  CAS  Google Scholar 

  • Todd, W. R., C. A. Elvehjem and E. B. Hart. 1934. Zinc in the nutrition of the rat. Am. J. Physiol. 197:146.

    Google Scholar 

  • Udom, A. O. and F. O. Brady. 1980. Reactivation in vitro of zinc-requiring apo-enzymes by rat liver zinc-thionein. Biochem. J. 187:326–335.

    Google Scholar 

  • Underwood, E. J. 1977. Zinc. Pp. 196–242 in Trace Elements in Human and Animal Nutrition. Academic Press, New York.

    Google Scholar 

  • Wacker, W. E. C. 1962. Nucleic acids and metals, III. Changes in nucleic acid, protein and metal content as a consequence of zinc deficiency in Euglena gracilis. Biochemistry 1:859–865.

    Article  PubMed  CAS  Google Scholar 

  • Wandzilak, T. M. and R. W. Benson. 1977. Yeast RNA polymerase III: a zinc metalloenzyme. Biochem. Biophys. Res. Comm. 76:247–252.

    Article  CAS  Google Scholar 

  • Wegener, W. S. and A. H. Romano. 1963. Zinc stimulation of RNA and protein synthesis in Rhizopus nigrican. Science 142:1669–1670.

    Article  PubMed  CAS  Google Scholar 

  • Weser, U. and E. Bichoff. 1970. Incorporation of 65 Zn in rat liver nuclei. Europ. Biochem. J. 12:571–575.

    Article  CAS  Google Scholar 

  • Williams, R. O. and L. A. Loeb. 1973. Zinc requirement for DNA replication in stimulated human lymphocytes. J. Cell Biol. 58:594–601.

    Article  PubMed  CAS  Google Scholar 

  • Williams, R. J. P. 1984. Zinc: what is its role in biology? Endeavor 8:65–70.

    Article  CAS  Google Scholar 

  • Wynshaw-Boris, A., T. G. Lugo, J. M. Short, R. E. K. Fournier and R. W. Hanson. 1984. Identification of a cAMP regulatory region in the gene for rat cytosolic phosphoenolypyruvate carboxykinase (GTP). J. Biol. Chem. 259:12161–21269.

    PubMed  CAS  Google Scholar 

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  1. Department of Food Science and Human Nutrition, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida, 32611, USA

    Robert J. Cousins

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  1. Animal Parasitology Institute Protozoan Diseases Laboratory, USDA Agricultural Research Service, Beltsville, MD, 20705, USA

    Harry D. Danforth

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© 1986 Martinus Nijhoff Publishers, Dordrecht

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Cousins, R.J. (1986). Molecular biology of zinc. In: Augustine, P.C., Danforth, H.D., Bakst, M.R. (eds) Biotechnology for Solving Agricultural Problems. Beltsville Symposia in Agricultural Research, vol 10. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-4396-4_16

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  • DOI: https://doi.org/10.1007/978-94-009-4396-4_16

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