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Chapter 13 : Nucleotide Metabolism

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Abstract:

A complete understanding of the nucleotide metabolism of is of fundamental interest to microbiology and also will help in the development of new anti- therapies. Pyrimidines and purines are essential for the synthesis of nucleoside triphosphates, which are precursors of nucleic acids. Nucleoside polyphosphates are formed by successive phosphorylations of their monophosphate counterparts. Pyrimidine ribonucleotide synthesis includes De Novo pyrimidine nucleotide synthesis, carbamoyl phosphate synthetase and aspartate carbamoyl transferase. The de novo synthesis of purine nucleotides is carried out by pathways that are similar throughout the biological world, but many organisms obtain their nucleotide needs utilizing preformed purine compounds through salvage pathways that take up available purine nucleobases and nucleosides. The thymidine triphosphate (dTTP) salvage pathway described in requires the presence of uridine phosphorylase or thymidine phosphorylase, and thymidine kinase, encoded by , , and genes, respectively. There are only a few studies on the nucleotide metabolism of , but together with the information derived from analyses of the genome of the bacterium, they have provided a wealth of information about the pathways of biosynthesis and degradation of pyrimidine and purine nucleotides, and showed that nucleotide biosynthetic enzymes are potential targets for antimicrobials designed against the organism.

Citation: Mendz G. 2001. Nucleotide Metabolism, p 147-158. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch13

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Nuclear Magnetic Resonance Spectroscopy
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Nucleoside Diphosphates
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Figures

Image of Figure 1
Figure 1

De novo pyrimidine biosynthesis pathway. The enzymes encoded by the genes are carbamoyl phosphate synthase; aspartate carbamoyl transferase; dihydroorotase; dihydroorotase dehydrogenase; orotate phosphoribosyltransferase; orotidylate decarboxylase; UMP kinase; nucleoside diphosphokinase; and CTP synthetase. The nucleotides are OMP, orotidine monophosphate; UMP, uridine monophosphate; UDP, uridine diphosphate; UTP, uridine triphosphate; and CTP, cytosine triphosphate.

Citation: Mendz G. 2001. Nucleotide Metabolism, p 147-158. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch13
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Image of Figure 2
Figure 2

De novo purine biosynthesis pathway. The enzymes encoded by the genes are glutamine:PRPP-amido-transferase; phosphoribosylglycinamide (GAR) synthetase; GAR transformylase N; GAR transformylase T; phosphoribosyl--formylglycinamide synthetase; phosphoribosyl-aminoimidazole synthetase; phosphoribosyl-carboxyaminoimidazole synthetase; phosphoribosyl-carboxyaminoimidazole mutase; phosphoribosyl--succino-carboxamide-aminoimidazole; adenylosuccinate lyase; phosphoribosyl-carboxamide-aminoimidazole transformylase; and inosinic acid cyclohydrolase. The compounds are Gln, glutamine; PPi, pyrophosphate; Glu, glutamate; ATP, adenosine triphosphate; ADP, adenosine diphosphate; Pi, phosphate; -Formyl-THF, -formyl-tetrahydrofolate; THF, tetrahydrofolate; CO, carbon dioxide; Asp, aspartate; and HO, water.

Citation: Mendz G. 2001. Nucleotide Metabolism, p 147-158. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch13
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Figure 3

De novo synthesis of ATP and GTP. The enzymes encoded by the different genes are IMP dehydrogenase; GMP synthase; GMP kinase; nucleoside diphosphokinase; adenylosuccinate synthetase; adenylosuccinate lyase; and adenylate kinase. The nucleotides are IMP, inosine monophosphate; XMP, xanthosine monophosphate; GMP, guanosine monophosphate; GDP, guanosine diphosphate; GTP, guanosine triphosphate; AMP, adenosine monophosphate; ADP, adenosine diphosphate; and ATP, adenosine triphosphate. The asterisk denotes a gene not identified in the genome or whose corresponding enzyme activity has not been observed.

Citation: Mendz G. 2001. Nucleotide Metabolism, p 147-158. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch13
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Figure 4

Salvage and interconversion of purines. The enzymes encoded by the different genes are purine nucleoside phosphorylase; adenine phosphoribosyl transferase; adenylosuccinate lyase; adenylosuccinate synthetase; GMP reductase; guanine phosphoribosyl transferase; IMP dehydrogenase; and GMP synthase. The purine bases are A, adenine; G, guanine; and Hx, hypoxanthine. Ribonucleosides and deoxyribonucleosides are identified by R and dR, respectively. Nucleotide monophosphates are identified by MP with XMP as xanthosine monophosphate. Nucleotide triphosphates are identified by TP. The asterisk represents a gene whose enzyme activity has not been detected.

Citation: Mendz G. 2001. Nucleotide Metabolism, p 147-158. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch13
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Figure 5

Biosynthesis of deoxyribonucleotides. The enzymes encoded by the different genes are ribonucleoside diphosphate reductase; nucleoside diphosphokinase; dCTP deaminase; deoxyuridine triphosphatase; thymidylate synthase; thymidylate kinase; and nucleoside diphosphokinase. In the nucleotides N can be A, C, and U; dNDP, deoxynucleoside diphosphate; dATP, deoxyadenosine triphosphate; dCTP, deoxycytidine triphosphate; dUTP, deoxyuridine tiphosphate; dUMP, deoxyuridine monophosphate; dTMP, deoxythymidine monophosphate; dTDP, deoxythymidine diphosphate; and dTTP, deoxythymidine triphosphate. The asterisk denotes a gene that has not been identified in the genome.

Citation: Mendz G. 2001. Nucleotide Metabolism, p 147-158. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch13
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