Skip to main content

Advertisement

SpringerLink
Log in

Enhancement of biotinidase activity in mouse serum by inhibitors of methylation

  • Original Article
  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Summary

DL-ethionine increases the activity of liver biotinidase, an enzyme which hydrolyzes biotinylesters and biotinylpeptides. Chronic DL-ethionine feeding increases transiently the activity of biotinidase in mouse and rat liver, after which it remains elevated in the serum. In the present work we show that both isomers of DL-ethionine are equally good enhancers of the liver biotinidase, while, 3-ethylthiopropionate, the toxic metabolite of DL-ethionine, has no effect on the biotinidase activity of either liver or serum. We have also employed two different combinations of inhibitors of the hydrolytic pathway of SAH, a transmethylation product and potent inhibitor of methylation. It was found that these inhibitors (EHNA and Ara-A, 2-deoxycoformycin and adenosine) increase the activity of serum biotinidase as was the case with ethionine. Because SAH does not ethylate biomolecules, these changes in biotinidase activity, which can not be preveneted by adenine, biotin or lecithin are most probably related to the inhibition of methylation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

Ara-A:

9-β-D-arabinofuranosyladenine

EHNA:

erythro-9-(2-hydroxy-3-nonyl)adenine

SAE:

S-adenosylethionine

SAH:

S-adenosylhomocysteine

SAM:

S-adenosylmethionine

References

  1. Popper H, de la Huerga J, Yesinic C: Hepatic tumors due to prolonged ethionine feeding. Science 118:80–82, 1953

    Google Scholar 

  2. Farber E: Ethionine carcinogenesis. Adv Cancer Res 7:383–474, 1963

    Google Scholar 

  3. Villa-Trevino S, Farber E: The reversal by adenosine triphosphate of ethionine-induced inhibition of protein synthesis. Biochim Biophys Acta 61:649–651, 1962

    Google Scholar 

  4. Shull KH, McConomy J, Vogt M, Castillo A, Farber E: On the mechanism of induction of hepatic adenosine triphosphate deficiency by ethionine. J Biol Chem 241:5060–5070, 1966

    Google Scholar 

  5. Cox R, Irwing CC: Inhibition of DNA methylation by S-adenosylethionine with the production of methyldeficient DNA in regenerating rat liver. Cancer Res 37:222–225, 1977

    Google Scholar 

  6. Tuck MT, Cox R: Ethionine inhibits in vivo methylation of nuclear proteins. Carcinogenesis 3:431–434, 1982

    Google Scholar 

  7. Wainfan E, Moller ML, Maschio FA, Balis ME: Ethionine-induced changes in rat liver transfer RNA methylation. Cancer Res 35:2830–2835, 1975

    Google Scholar 

  8. Takahashi Y, Ogata K: Effects of ethionine on proteinsynthesizing apparatus of rat liver 80 S ribosomes and 40 S ribosomal subunits. Biochim Biophys Acta 697:101–112, 1982

    Google Scholar 

  9. Kisilevsky R: The regulatory parameter of protein synthesis most affected by ethionine and cycloheximide. Biochim Biophys Acta 272:463–472, 1972

    Google Scholar 

  10. Hase M, Endo Y, Natori Y: The role of translational inhibitor in ethionine-induced inhibition of protein synthesis. Biochim Acta 698:102–104, 1982

    Google Scholar 

  11. Farber E: Ethionine fatty liver. Adv Lipid Res 5:119–183, 1967

    Google Scholar 

  12. Kisilevsky R, Weiler L: Microsomal membrane alterations during acute ethionine toxicity and carcinogenesis. Exp Mol Path 24: 193–200, 1976

    Google Scholar 

  13. Pispa J, Koivusalo M: Actinomycin D-sensitive increase in the biotinidase activity in mouse liver and serum after ethionine feeding. Acta Chem Scand 26:2133–2135, 1972

    Google Scholar 

  14. Pispa J: Animal biotinidase. Ann Med Exp Biol Fenn Suppl 5:5–39, 1965

    Google Scholar 

  15. Kasperczyk H, Koj A: Ethionine-dependent inhibition of acute-phase plasma protein synthesis in the rat. Br J Exp Path 64:277–285, 1983

    Google Scholar 

  16. Christman JK, Price P, Pedrinan L, Acs G: Correlation between hypomethylation of DNA and expression of globin genes in Friend erythroleukemia cells. Eur J Biochem 81:53–61, 1977

    Google Scholar 

  17. Boehm TLJ, Drahovsky D: Elevated transcriptional complexity and decrease in enzymatic DNA methylation in cells treated with methionine. Cancer Res 41:4101–4106, 1982

    Google Scholar 

  18. Tsukada K, Yamano H, Tetsuaki A, Okada G: Ethionine-induced changes in the activities of S- adenosylmethionine synthetase isozymes from rat liver. Biochem Biophys Res Comm 95:1160–1167, 1980

    Google Scholar 

  19. Palomaa MH, Kaski T: Studien uber ätherartige Verbindungen. XXX. Mitteilung: Die Veresterungs- und Verseifungsgeschwindigkeit einiger Thioäthersäuren. Suomen Kemistilehti 19:85–88, 1946

    Google Scholar 

  20. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275, 1951

    CAS  PubMed  Google Scholar 

  21. Brada Z, Bulba S: In vivo D-ethionine inversion and its inhbition. Res Comm Chem Pathol Pharmacol 30:341–360, 1980

    Google Scholar 

  22. Steele RD: Role of 3-ethylthiopropionate in ethionine metabolism and toxicity in rats. J Nutr 112:118–125, 1982

    Google Scholar 

  23. Orenstein JM, Marsh WH: Incorporation in vivo of methionine and ethionine into and the methylation and ethylation of rat liver nuclear proteins. Biochem J 109:697–699, 1968

    Google Scholar 

  24. Tuck MT, Cox R: Ethionine causes the formation of NG-monoethylarginine in nuclear proteins from regenerating rat liver. Carcinogenesis 12:1477–1480, 1982

    Google Scholar 

  25. Ortwerth BJ, Novelli GD: Studies on the incorporation of methionine-1–14C into the transfer RNA of rat liver. Cancer Res 29:380–390, 1969

    Google Scholar 

  26. Cantoni GL: The nature of the active methyl donor formed enzymatically from Lrmethionine and adenosinetriphosphate. J Am Chem Soc 74:2942–2943, 1952

    Google Scholar 

  27. Ueland PM: Pharmacological and Biochemical aspects of S-adenosylhomocysteine and S-adenosylhomocyteine hydrolase. Pharmacological Reviews 3:223–253, 1982

    Google Scholar 

  28. Hoffman RM: Altered methionine metabolism, DNA methylation and oncogene expression in carcinogenesis. A review and synthesis. Biochim Biophys Acta 738:49–87, 1984

    Google Scholar 

  29. Smith RC, Salmon WD: Formation of S-adenosylethionine by ethionine-treated rats. Arch Biochem Biophys 111:191–196, 1965

    Google Scholar 

  30. Hoffman DR, Marion DW, Cornatzer WE, Duerre JA: S-adenosylmethionine and S-adenosylhomocysteine metabolism in isolated rat liver. Effects of L-methionine, L-homocysteine and adenosine. J Biol Chem 255:10822–10827, 1980

    Google Scholar 

  31. De la Haba G, Cantoni GL: The enzymatic synthesis of S-adenosyl-L-homocysteine from adenosine and homocysteine. J Biol Chem 234:603–608, 1959

    Google Scholar 

  32. Schatz RA, Vunnam CR, Sellinger OZ: Species and tissue differences in the catabolism of S-adenosyl-L-homocysteine: A quatitative, chromatographic study. Life Sci 20:375–384, 1977

    Google Scholar 

  33. Eloranta TO, Kajander EO, Raina AM: Effect of 9-β-D-Arabinofuranosyladenine and erythro-9-(2-hydroxy-3-nonyl)adenine on the metabolism of S-adenosylhomocysteine, S-adenosylmethionine and adenosine in rat liver. Med Biol 60:272–277, 1982

    Google Scholar 

  34. Helland S, Ueland PM: S-adenosylhomocysteine and Sadenosylhomocysteine hydrolase in various tissues of mice given injections of 9-βD-arabinofuranosyladenine. Cancer Res 43:1847–1850, 1983

    Google Scholar 

  35. Agarwal RP, Spector T, Parks RE: Tight-binding inhibitors. IV Inhibition of adenosine deaminase by various inhibitors. Biochem Pharmacol 26:359–367, 1977

    Google Scholar 

  36. Plunkett W, Alexander L, Chubb S, Liloo T: Comparison of the activity of 2-deoxycofromycin and erythro-9-(2-hydroxy-3-nonyl)adenine in vivo. Biochem Pharmacol 28:201–206, 1979

    Google Scholar 

  37. Glough DW, Kunkel LM, Davidson RL: 5-azacytidine induced reactivation of a herpes simplex thymidine kinase gene. Science 216:70–73, 1982

    Google Scholar 

  38. Zucker RM, Decal DL, Whittington KB: 5-Azacytidine increases the synthesis of embryonic hemoglobin (E2) in murine erythroleukemic cells. FEBS Letters 162:436–441, 1983

    Google Scholar 

  39. Charache S, Dover G, Smith K, Talbot CC, Moyer M, Boyer S: Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the γ-δ-β-globin gene complex. Proc Natl Acad Sci USA 80:4842–4846, 1983

    Google Scholar 

  40. Ley TJ, Desimone J, Anagnou NP, Keller GH, Humphies RK, Turner PA, Young NS, Heller P, Nienhuis AW: 5-azacytidine selectively increases globin synthesis in a patient with β+thalassemia. N Eng J Med 307:1469–1475, 1982

    Google Scholar 

  41. Creusot F, Acs G, Christman JK: Inhibition of DNA methyltransferase and induction of Friend erythroleukemia differentiation by 5-azacytidine and 5-aza-2-deoxycytidine. J Biol Chem 257:2041–2048, 1982

    Google Scholar 

  42. Pilar FM, Young MF, Sobel ME: Methylation of type II and type I collagen genes in differentiated and dedifferentiated chrondrocytes. J Biol Chem 4:2374–2378, 1985

    Google Scholar 

  43. Petropoulos CJ, Yaswen P, Panzica M, Fausto N: Methylation of alphafetoprotein gene in cell populations isolated from rat livers during carcinogenesis. Nucleic Acids Res 22:8105–8118, 1985

    Google Scholar 

  44. Burch JBE; Weintraub H: Temporal order of chromatin structural changes associated with activation of the major chicken vitellogenin gene. Cell 33:65–76, 1983

    Google Scholar 

  45. McKeon C, Ohkubo H, Postan I, DeCrombrugghe B: Unusual methylation pattern of the α2(1)collagen gene. Cell 29:203–210, 1982

    Google Scholar 

  46. Rothrock R, Perry ST, Isham KR, Lee K-L, Kenney FT: Activation of tyrosine aminotransferase expression in fetal liver by 5-azacytidine. Biochem Biophys Res Comm 113:645–649, 1983

    Google Scholar 

  47. Cook JK, Chiu J-F: Effect of 5-azacytidine on rat liver alpha-fetoprotein gene expression. Biochem Biophys Res Comm 116:939–944, 1983

    Google Scholar 

  48. Cihak A: Biological effects of 5 Azacytidine in eukaryotes. Oncology 30:405–422, 1974

    Google Scholar 

  49. Robinson DS, Harris M: Ethionine administration in the rat. Effects on the incorporation of 32porthophosphate and DL- 1–14C leucine into the phosphatides and proteins of liver and plasma. Biochem J 80:361–369, 1961

    Google Scholar 

  50. Best CB: Protection of liver and kidneys by dietory factors choline and its precursors as lipotropic agents. Federation Proc 9:506–511, 1950

    Google Scholar 

  51. Stekol JA, Weiss S, Somerville C: A study of the comparative metabolism of ethionine and methionone in the male and female rat. Arch Biochem Biophys 100:86–90, 1963

    Google Scholar 

  52. Lyman RL, Sheehan G, Tinoco J: Phosphatidylethanolamine metabolism in rats fed a low methionine, choline deficient diet. Lipids 8:71–79, 1973

    Google Scholar 

  53. Sastry RBV, Statham RN, Axelrod J, Hirata F: Evidence for two methyltransferases involved in the conversion of phosphatidylethanolamine to phosphatidylcholine in the rat liver. Arch Biochem Biophys 211:762–773, 1981

    Google Scholar 

  54. Pascale R, Pirisi L, Paino L, Zanetti S, Satta A, Bartoli E, Feo F: Role of phosphatidylethanolamine methylation in the synthesis of phosphatidylcholine by hepatocytes isolataed from choline-deficient rats. FEBS Letters 145:293–297, 1982

    Google Scholar 

  55. Edwards AM, Sabine JR: Metabolic controls in precancerous liver — VI. Studies in vivo and in vitro on feedback regulation of delta-aminolevulinic acid synthetase in ethioninefed rats. Eur J Cancer 10:793–800, 1974

    Google Scholar 

  56. Bowers-Komro DM, McCormick DB: Biotin uptake by isolated rat liver hepatocytes. In: Biotin. Dakshinamurti K, Bhagavan HN (eds) Ann NY Acad Sci 447:350–358, 1985

  57. Ullman B, Oudes LJ, Cohen A, Martin Jr DV: Deoxyadenosine metabolism and cytotoxicity in cultured mouse T lymphoma cells: a model for immunodeficiency disease. Cell 14:360–375, 1978

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Chemistry, University of Helsinki, Siltavuorenpenger 10, SF-00170, Helsinki, Finland

    Vesa P. Kontinen & Jaakko P. Pispa

Authors
  1. Vesa P. Kontinen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jaakko P. Pispa
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kontinen, V.P., Pispa, J.P. Enhancement of biotinidase activity in mouse serum by inhibitors of methylation. Mol Cell Biochem 76, 85–91 (1987). https://doi.org/10.1007/BF00219401

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00219401

Key words

Search

Navigation