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. 1966 Mar;91(3):1037–1049. doi: 10.1128/jb.91.3.1037-1049.1966

Metabolism of Methylated Purines in Escherichia coli: Derepression of Purine Biosynthesis

Samuel H Love 1, Charles N Remy 2
PMCID: PMC315995  PMID: 5326092

Abstract

Love, Samuel H. (Bowman Gray School of Medicine, Wake Forest College, Winston-Salem, N.C.), and Charles N. Remy. Metabolism of methylated purines in Escherichia coli: derepression of purine biosynthesis. J. Bacteriol. 91:1037–1049. 1966.—Various methylated purines were examined for their effects on growth of purine-requiring mutants of Escherichia coli, strains W-11 and B-96, and for their effects on purine biosynthesis. 6-Methylaminopurine and 6-methoxypurine stimulated the accumulation of purine precursor derivatives (ribosyl-5-aminoimidazole and ribosyl-5-amino-4-imidazole carboxamide) beyond their ability to support growth. Information obtained from in vivo and in vitro systems demonstrated that the metabolism of 6-methylaminopurine and 6-methoxypurine utilized identical pathways. The riboside derivatives are formed either by direct ribosidation via nucleoside phosphorylase or, indirectly, by dephosphorylation of the 5′-phosphoribosyl derivatives which are synthesized via adenylate pyrophosphorylase. Information obtained with the aid of strain W-11/DAP (lacking adenylate pyrophosphorylase) demonstrated that both pathways were important to the growing cells. Regardless of the metabolic pathway by which they are synthesized, the ribosyl derivatives are demethylaminated (demethylated) by adenosine deaminase to yield inosine. The final conversion of inosine to inosinic acid via the intermediate formation of hypoxanthine accounts for the net conversion of the methylated bases to inosinic acid. The utilization of the bases is sufficiently rate-limiting to cause derepression of the early enzymes required for the de novo synthesis of purine, thus accounting for the elevated accumulation of purine precursors originally observed.

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Selected References

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

  1. AMES B. N., GARRY B., HERZENBERG L. A. The genetic control of the enzymes of histidine biosynthesis in Salmonella typhimurium. J Gen Microbiol. 1960 Apr;22:369–378. doi: 10.1099/00221287-22-2-369. [DOI] [PubMed] [Google Scholar]
  2. DUGGAN D. E., TITUS E. The utilization of 6-methylaminopurine by mammalian tissues. Biochim Biophys Acta. 1962 Jan 22;55:273–275. doi: 10.1016/0006-3002(62)90973-3. [DOI] [PubMed] [Google Scholar]
  3. FLEISSNER E., BOREK E. A new enzyme of RNA synthesis: RNA methylase. Proc Natl Acad Sci U S A. 1962 Jul 15;48:1199–1203. doi: 10.1073/pnas.48.7.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. FLEISSNER E., BOREK E. STUDIES ON THE ENZYMATIC METHYLATION OF SOLUBLE RNA. I. METHYLATION OF THE S-RNA POLYMER. Biochemistry. 1963 Sep-Oct;2:1093–1100. doi: 10.1021/bi00905a032. [DOI] [PubMed] [Google Scholar]
  5. GOLD M., HURWITZ J. THE ENZYMATIC METHYLATION OF RIBONUCLEIC ACID AND DEOXYRIBONUCLEIC ACID. V. PURIFICATION AND PROPERTIES OF THE DEOXYRIBONUCLEIC ACID-METHYLATING ACTIVITY OF ESCHERICHIA COLI. J Biol Chem. 1964 Nov;239:3858–3865. [PubMed] [Google Scholar]
  6. GOTS J. S., CHU E. C. Studies on purine metabolism in bacteria. I. The role of p-aminobenzoic acid. J Bacteriol. 1952 Oct;64(4):537–546. doi: 10.1128/jb.64.4.537-546.1952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. GOTS J. S., LOVE S. H. Purine metabolism in bacteria. II. Factors influencing biosynthesis of 4-amino-5-imidazolecarboxamide by Escherichia coli. J Biol Chem. 1954 Sep;210(1):395–405. [PubMed] [Google Scholar]
  8. GOTS J. S. Purine metabolism in bacteria. V. Feed-back inhibition. J Biol Chem. 1957 Sep;228(1):57–66. [PubMed] [Google Scholar]
  9. Gold M., Hurwitz J., Anders M. THE ENZYMATIC METHYLATION OF RNA AND DNA, II. ON THE SPECIES SPECIFICITY OF THE METHYLATION ENZYMES. Proc Natl Acad Sci U S A. 1963 Jul;50(1):164–169. doi: 10.1073/pnas.50.1.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. HURWITZ J., ANDERS M., GOLD M., SMITH I. THE ENZYMATIC METHYLATION OF RIBONUCLEIC ACID AND DEOXYRIBONUCLEIC ACID. VII. THE METHYLATION OF RIBONUCLEIC ACID. J Biol Chem. 1965 Mar;240:1256–1266. [PubMed] [Google Scholar]
  11. HURWITZ J., GOLD M., ANDERS M. THE ENZYMATIC METHYLATION OF RIBONUCLEIC ACID AND DEOXYRIBONUCLEIC ACID. IV. THE PROPERTIES OF THE SOLUBLE RIBONUCLEIC ACID-METHYLATING ENZYMES. J Biol Chem. 1964 Oct;239:3474–3482. [PubMed] [Google Scholar]
  12. KOCH A. L., VALLEE G. The properties of adenosine deaminase and adenosine nucleoside phosphorylase in extracts of Escherichia coli. J Biol Chem. 1959 May;234(5):1213–1218. [PubMed] [Google Scholar]
  13. KURAMITSU H. K., UDAKA S., MOYED H. S. INDUCTION OF INOSINE 5'-PHOSPHATE DEHYDROGENASE AND XANTHOSINE 5'-PHOSPHATE AMINASE BY RIBOSYL-4-AMINO-5-IMIDAZOLECARBOXAMIDE IN PURINE-REQUIRING MUTANTS OF ESCHERICHIA COLI B. J Biol Chem. 1964 Oct;239:3425–3430. [PubMed] [Google Scholar]
  14. LOVE S. H., GOTS J. S. Purine metabolism in bacteria. III. Accumulation of a new pentose-containing arylamine by a purine-requiring mutant of Escherichia coli. J Biol Chem. 1955 Feb;212(2):647–654. [PubMed] [Google Scholar]
  15. MAGASANIK B., KARIBIAN D. Purine nucleotide cycles and their metabolic role. J Biol Chem. 1960 Sep;235:2672–2681. [PubMed] [Google Scholar]
  16. MANDEL L. R., BOREK E. THE BIOSYNTHESIS OF METHYLATED BASES IN RIBONUCLEIC ACID. Biochemistry. 1963 May-Jun;2:555–560. doi: 10.1021/bi00903a029. [DOI] [PubMed] [Google Scholar]
  17. MARKHAM R., SMITH J. D. Chromatographic studies of nucleic acids; a technique for the identification and estimation of purine and pyrimidine bases, nucleosides and related substances. Biochem J. 1949;45(3):294–298. doi: 10.1042/bj0450294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. MCCOLLISTER R. J., GILBERT W. R., Jr, ASHTON D. M., WYNGAARDEN J. B. PSEUDOFEEDBACK INHIBITION OF PURINE SYNTHESIS BY 6-MERCAPTOPURINE RIBONUCLEOTIDE AND OTHER PURINE ANALOGUES. J Biol Chem. 1964 May;239:1560–1563. [PubMed] [Google Scholar]
  19. MOYED H. S., MAGASANIK B. The biosynthesis of the imidazole ring of histidine. J Biol Chem. 1960 Jan;235:149–153. [PubMed] [Google Scholar]
  20. NIERLICH D. P., MAGASANIK B. REGULATION OF PURINE RIBONUCLEOTIDE SYNTHESIS BY END PRODUCT INHIBITION. THE EFFECT OF ADENINE AND GUANINE RIBONUCLEOTIDES ON THE 5'-PHOSPHORIBOSYL-PYROPHOSPHATE AMIDOTRANSFERASE OF AEROBACTER AEROGENES. J Biol Chem. 1965 Jan;240:358–365. [PubMed] [Google Scholar]
  21. PETERKOFSKY A., JESENSKY C., BANK A., MEHLER A. H. STUDIES ON THE ROLE OF METHYLATED BASES IN THE BIOLOGICAL ACTIVITY OF SOLUBLE RIBONUCLEIC ACID. J Biol Chem. 1964 Sep;239:2918–2926. [PubMed] [Google Scholar]
  22. REMY C. N. Metabolism of 6-methylaminopurine: synthesis and demethylation by Escherichia coli. J Biol Chem. 1961 Nov;236:2999–3005. [PubMed] [Google Scholar]
  23. REMY C. N., SMITH M. S. Metabolism of 2, 6-diaminopurine; conversion to 5'-phosphoribosyl-2-methylamino-beta-aminopurine by enzymes of Escherichia coli. J Biol Chem. 1957 Sep;228(1):325–338. [PubMed] [Google Scholar]
  24. STARR J. L., FEFFERMAN R. THE OCCURRENCE OF METHYLATED BASES IN RIBOSOMAL RIBONUCLEIC ACID OF ESCHERICHIA COLI K12 W-6. J Biol Chem. 1964 Oct;239:3457–3461. [PubMed] [Google Scholar]
  25. STARR J. L. Studies on the methylation of soluble ribonucleic acid. I. Failure of the direct incorporation of 6-methylaminopurine. Biochim Biophys Acta. 1962 Nov 26;61:676–680. doi: 10.1016/0926-6550(62)90051-8. [DOI] [PubMed] [Google Scholar]
  26. STARR J. L. The incorporation of amino acids into "methyl-poor" amino acid transfer ribonucleic acid. Biochem Biophys Res Commun. 1963 Jan 31;10:181–185. doi: 10.1016/0006-291x(63)90047-0. [DOI] [PubMed] [Google Scholar]
  27. UDAKA S., MOYED H. S. INHIBITION OF PARENTAL AND MUTANT XANTHOSINE 5'-PHOSPHATE AMINASES BY PSICOFURANINE. J Biol Chem. 1963 Aug;238:2797–2803. [PubMed] [Google Scholar]
  28. ZIMMERMAN E. F., MAGASANIK B. UTILIZATION AND INTERCONVERSION OF PURINE BASES AND RIBONUCLEOSIDES BY SALMONELLA TYPHIMURIUM. J Biol Chem. 1964 Jan;239:293–300. [PubMed] [Google Scholar]

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