Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1972 Jul;128(4):869–877. doi: 10.1042/bj1280869

The control of nucleic acid and nicotinamide nucleotide synthesis in regenerating rat liver

G M Ferris 1, J B Clark 1
PMCID: PMC1173907  PMID: 4404767

Abstract

1. The effect of injecting nicotinamide on the incorporation of [14C]orotate into the hepatic nucleic acids of rats after partial hepatectomy was investigated. 2. At 3h after partial hepatectomy the rapid incorporation of [14C]orotate into RNA, and at 20h after partial hepatectomy the incorporation of [14C]orotate into both RNA and DNA, were inhibited in a dose-dependent fashion by the previous injection of nicotinamide. 3. The injection of nicotinamide at various times before the injection of [14C]orotate at 20h after partial hepatectomy revealed an inhibition of the incorporation of orotate into RNA and DNA which was non-linear with respect to the duration of nicotinamide pretreatment. 4. The induction of a hepatic ATP depletion by ethionine demonstrated that the synthesis of hepatic NAD and NADP in partially hepatectomized rats was more susceptible to an ATP deficiency than in control rats. 5. The total hepatic activity of ribose phosphate pyrophosphokinase (EC 2.7.6.1) was assayed at various times after partial hepatectomy and found to be only marginally greater than the maximum rate of hepatic NAD synthesis induced in vivo by nicotinamide injection between 12 and 24h after partial hepatectomy. 6. It is suggested that a competition exists between NAD synthesis and purine and pyrimidine nucleotide synthesis for available ATP and particularly 5-phosphoribosyl 1-pyrophosphate. In regenerating liver the competition is normally in favour of the synthesis of nucleic acid precursors, at the expense of NAD synthesis. This situation may be reversed by the injection of nicotinamide with a subsequent inhibition of nucleic acid synthesis.

Full text

PDF
870

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BUCHER N. L. REGENERATION OF MAMMALIAN LIVER. Int Rev Cytol. 1963;15:245–300. doi: 10.1016/s0074-7696(08)61119-5. [DOI] [PubMed] [Google Scholar]
  2. BURTON K. The relation between the synthesis of deoxyribonucleic acid and the synthesis of protein in the multiplication of bacteriophage T2. Biochem J. 1955 Nov;61(3):473–483. doi: 10.1042/bj0610473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bucher N. L. Experimental aspects of hepatic regeneration. N Engl J Med. 1967 Sep 28;277(13):686–contd. doi: 10.1056/NEJM196709282771306. [DOI] [PubMed] [Google Scholar]
  4. Bucher N. L. Experimental aspects of hepatic regeneration. N Engl J Med. 1967 Oct 5;277(14):738–concl. doi: 10.1056/NEJM196710052771405. [DOI] [PubMed] [Google Scholar]
  5. Burzio L., Koide S. S. A functional role of polyADPR in DNA synthesis. Biochem Biophys Res Commun. 1970 Sep 10;40(5):1013–1020. doi: 10.1016/0006-291x(70)90894-6. [DOI] [PubMed] [Google Scholar]
  6. Burzio L., Koide S. S. Mode of inhibition of DNA synthesis induced by adenosine diphosphoribosylation of nuclear protein. Biochem Biophys Res Commun. 1971 Mar 19;42(6):1185–1190. doi: 10.1016/0006-291x(71)90031-3. [DOI] [PubMed] [Google Scholar]
  7. CERIOTTI G. Determination of nucleic acids in animal tissues. J Biol Chem. 1955 May;214(1):59–70. [PubMed] [Google Scholar]
  8. Clark J. B., Ferris G. M., Pinder S. Inhibition of nuclear NAD nucleosidase and poly ADP-ribose polymerase activity from rat liver by nicotinamide and 5'-methyl nicotinamide. Biochim Biophys Acta. 1971 Apr 29;238(1):82–85. doi: 10.1016/0005-2787(71)90012-8. [DOI] [PubMed] [Google Scholar]
  9. Clark J. B., Pinder S. Control of the steady-state concentrations of the nicotinamide nucleotides in rat liver. Biochem J. 1969 Sep;114(2):321–330. doi: 10.1042/bj1140321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. FLAKS J. G., ERWIN M. J., BUCHANAN J. M. Biosynthesis of the purines. XVIII. 5-Amino-1-ribosyl-4-imidazolecarboxamide 5'-phosphate transformylase and inosinicase. J Biol Chem. 1957 Dec;229(2):603–612. [PubMed] [Google Scholar]
  11. FLECK A., MUNRO H. N. The precision of ultraviolet absorption measurements in the Schmidt-Thannhauser procedure for nucleic acid estimation. Biochim Biophys Acta. 1962 May 14;55:571–583. doi: 10.1016/0006-3002(62)90836-3. [DOI] [PubMed] [Google Scholar]
  12. FUJIOKA M., KOGA M., LIEBERMAN I. METABOLISM OF RIBONUCLEIC ACID AFTER PARTIAL HEPATECTOMY. J Biol Chem. 1963 Oct;238:3401–3406. [PubMed] [Google Scholar]
  13. Ferris G. M., Clark J. B. Nicotinamide nucleotide synthesis in regenerating rat liver. Biochem J. 1971 Feb;121(4):655–662. doi: 10.1042/bj1210655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. GREENBAUM A. L., CLARK J. B., MCLEAN P. THE ESTIMATION OF THE OXIDIZED AND REDUCED FORMS OF THE NICOTINAMIDE NUCLEOTIDES. Biochem J. 1965 Apr;95:161–166. doi: 10.1042/bj0950161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. GREENGARD P., QUINN G. P., REID M. B. PITUITARY INFLUENCE OF PYRIDINE NUCLEOTIDE METABOLISM OF RAT LIVER. J Biol Chem. 1964 Jun;239:1887–1892. [PubMed] [Google Scholar]
  16. HENDERSON J. F., KHOO M. K. AVAILABILITY OF 5-PHOSPHORIBOSYL 1-PYROPHOSPHATE FOR RIBONUCLEOTIDE SYNTHESIS IN EHRLICH ASCITES TUMOR CELLS IN VITRO. J Biol Chem. 1965 Jun;240:2358–2362. [PubMed] [Google Scholar]
  17. HENDERSON J. F., KHOO M. K. SYNTHESIS OF 5-PHOSPHORIBOSYL 1-PYROPHOSPHATE FROM GLUCOSE IN EHRLICH ASCITES TUMOR CELLS IN VITRO. J Biol Chem. 1965 Jun;240:2349–2357. [PubMed] [Google Scholar]
  18. Hirsch C. A. Quantitative determination of the ribosomal ribonucleic acid content of liver and Novikoff hepatoma from fed and from fasted rats. J Biol Chem. 1967 Jun 25;242(12):2822–2827. [PubMed] [Google Scholar]
  19. KAPLAN N. O., GOLDIN A., HUMPHREYS S. R., STOLZENBACH F. E. Pyridine precursors of mouse liver diphosphopyridine nucleotide. J Biol Chem. 1957 May;226(1):365–371. [PubMed] [Google Scholar]
  20. LIEBERMAN I., KANE P. SYNTHESIS OF RIBOSOMES IN THE LIVER AFTER PARTIAL HEPATECTOMY. J Biol Chem. 1965 Apr;240:1737–1741. [PubMed] [Google Scholar]
  21. MORTON R. K. Enzymic synthesis of coenzyme I in relation to chemical control of cell growth. Nature. 1958 Feb 22;181(4608):540–542. doi: 10.1038/181540a0. [DOI] [PubMed] [Google Scholar]
  22. Murray A. W. Inhibition of purine phosphoribosyltransferases from Ehrlich ascites-tumour cells by purine nucleotides. Biochem J. 1966 Sep;100(3):671–674. doi: 10.1042/bj1000671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nishizuka Y., Ueda K., Nakazawa L., Reeder R. H., Honjo T. Poly adenosine diphosphate ribose synthesis and nicotinamide adenine dinucleotide transglycosidases. J Vitaminol (Kyoto) 1968 Mar 5;14(Suppl):143–152. doi: 10.5925/jnsv1954.14.supplement_143. [DOI] [PubMed] [Google Scholar]
  24. OIDE H. The influence of the intrasplenic implantation of nicotinamide on the mitotic activity and the phosphopyridine nucleotide content of regenerating liver. Gan. 1958 Mar;49(1):49–56. [PubMed] [Google Scholar]
  25. Ove P., Takai S. I., Umeda T., Lieberman I. Adenosine triphosphate in liver after partial hepatectomy and acute stress. J Biol Chem. 1967 Nov 10;242(21):4963–4971. [PubMed] [Google Scholar]
  26. Pinder S., Clark J. B. The effect of ATP on the synthesis of the nicotinamide nucleotides. FEBS Lett. 1968 Sep;1(4):206–208. doi: 10.1016/0014-5793(68)80061-4. [DOI] [PubMed] [Google Scholar]
  27. Preiss J., Schlaeger R., Hilz H. Specific inhibition of poly adpribose polymerase by thymidine and nicotinamide in HeLa cells. FEBS Lett. 1971 Dec 15;19(3):244–246. doi: 10.1016/0014-5793(71)80524-0. [DOI] [PubMed] [Google Scholar]
  28. REVEL M., MANDEL P. Effect of an induced synthesis of pyridine nucleotides in vivo on the metabolism of ribonucleic acid. Cancer Res. 1962 May;22:456–462. [PubMed] [Google Scholar]
  29. Rajalakshmi S., Handschumacher R. E. Control of purine biosynthesis de novo by orotic acid in vivo and in vitro. Biochim Biophys Acta. 1968 Feb 26;155(2):317–325. doi: 10.1016/0005-2787(68)90176-7. [DOI] [PubMed] [Google Scholar]
  30. Stirpe F., Corte E. D. Activity of nicotinamide-adenine dinucleotide pyrophosphorylase in liver nuclei. Effects of partial hepatectomy, hepatotoxins and dietary changes. Biochem J. 1968 Jun;108(1):89–93. doi: 10.1042/bj1080089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Villa-Trevino S., Shull K. H., Farber E. The inhibition of liver ribonucleic acid synthesis by ethionine. J Biol Chem. 1966 Oct 25;241(20):4670–4674. [PubMed] [Google Scholar]
  32. WINDMUELLER H. G. HEPATIC NUCLEOTIDE LEVELS AND NAD-SYNTHESIS AS INFLUENCED BY DIETARY OROTIC ACID AND ADENINE. J Nutr. 1965 Mar;85:221–229. doi: 10.1093/jn/85.3.221. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES