Guanosine triphosphate synthesis

The answer is e. (Katzung, p 842.) Ribavirin most likely interferes with guanosine triphosphate synthesis, resulting in inhibition of capping of viral messenger RNA and viral RN A-dependent RNA polymerase. It is effective in moderating infections with respiratory syncytial virus. 

Another triphosphate synthesis is described in reference [94], where a partially protected hexaribonucleotide derivative is converted by CDI into the imidazolide and subsequently condensed with a protected 7-methyl guanosine diphosphate to give the triphosphate. 

The product succinyl-CoA is able to participate in ATP synthesis as an example of substrate-level phosphorylation - we met some other examples in the glycolytic pathway. Essentially, hydrolysis of succinyl-CoA liberates snfficient energy that it can be coupled to the synthesis of ATP from ADP. However, guanosine triphosphate (GTP) is the... 

It is a guanosine analog which probably interferes with the synthesis of guanosine triphosphate, inhibiting capping of viral mRNA and to inhibit the viral RNA-dependent RNA polymerase. 

L3. Lieberman, I., Involvement of guanosine triphosphate in the synthesis of adenylosuccinate from inosine-5 -phosphate. /. Am. Chem. Soc. 78, 251 (1956). 

The aminoacyl transfer reaction, one of the latter stages in protein synthesis, involves incorporation of amino acids from soluble ribonucleic acid-amino acid into ribosomal protein. This reaction requires guanosine triphosphate and a soluble portion of the cell. Evidence has been obtained with rat liver preparations that aminoacyl transfer is catalyzed by two protein factors, aminoacyl transferases (or polymerases) I and n, which have been resolved and partially purified from the soluble fraction. Transferase n activity has also been obtained from deoxycholate-soluble extracts of microsomes. With purified transferases I and n, incorporation is observed with relatively low levels of GTP its sulfhy-dryl requirement is met by a variety of compounds. The characteristics of this purified amino acid incorporating system, in terms of dependency on the concentration of its components, are described. 

Jhe synthesis of proteins, as characterized by the in vitro incorporation of amino acids into the protein component of cytoplasmic ribonu-cleoprotein, is known to require the nonparticulate portion of the cytoplasm, ATP (adenosine triphosphate) and GTP (guanosine triphosphate) (15, 23). The initial reactions involve the carboxyl activation of amino acids in the presence of amino acid-activating enzymes (aminoacyl sRNA synthetases) and ATP, to form enzyme-bound aminoacyl adenylates and the enzymatic transfer of the aminoacyl moiety from aminoacyl adenylates to soluble ribonucleic acid (sRNA) which results in the formation of specific RNA-amino acid complexes—see, for example, reviews by Hoagland (12) and Berg (1). The subsequent steps in pro-... 

The precursors for riboflavin biosynthesis in plants and microorganisms are guanosine triphosphate and ribulose 5-phosphate. As shown in Figure 7.3, the first step is hydrolytic opening of the imidazole ring of GTP, with release of carbon-8 as formate, and concomitant release of pyrophosphate. This is the same as the first reaction in the synthesis ofpterins (Section 10.2.4), but utilizes a different isoenzyme of GTP cyclohydrolase (Bacher et al., 2000, 2001). 

Dietary purines are largely catabolized in the gut, rather than used by the body for the synthesis of nucleic acids. The end-product of purine catabolism in humans is uric add. The diet accounts f[ir less than half of the uric add appearing in the bloodstream, Most of the plasma uric add, or urate, originates from catabolism of the purines synthesized by the body (endogenous purines). The major purines are adenine and guanine. They occur mainly as nucleotides, such as adenosine triphosphate (ATP) and guanosine triphosphate (GTP), and as parts of nucleic acids. For example, the adenine in (UvfA occurs as adenosine monophosphate, and the adenine in DNA occurs as deoxyadenosine monophosphate. 

Guanosine triphosphate (GTP) is required by which of the following steps in protein synthesis ... 

Guanosine triphosphate and ribulose-5-phosphate are recruited in a 1 2 stoichiometric ratio by GTP cyclohydrolase II and DHBP synthase, respectively, for riboflavin biosynthesis. Since at substrate saturation the activity of B. subtilis DHBP is twice the activity of B. suhtilis cyclohydrolase II (DSM, unpublished observations) and since both enzymatic activities are associated with the same bifunctional protein encoded by rihA, the balanced formation of the pyrimidinedione and the dihydroxybutanone intermediates is ensured. However, the ifg.s constant of DHBP synthase ( 1 mmol is about 100-fold higher than the ifg.s constant of GTP cyclohydrolase II imposing the risk of excessive synthesis of the pyrimidinone and pyrimidinedione intermediates in case of reduced intracellular concentrations of pentose phosphate pathway intermediates. This can be expected, for instance, in glucose-limited fed-batch fermentations, which are frequentiy used in industrial applications. The pyrimidinone and pyrimidinedione intermediates are highly reactive, oxidative compounds, which can do serious damage on the bacteria. 

Ribavirin monophosphate competitively inhibits cellular inosine-5 -phosphate dehydrogenase and interferes with the synthesis of guanosine triphosphate (GTP) and, thus, nucleic acid synthesis in general. Ribavirin triphosphate also competitively inhibits the GTP-dependent 5 -capping of viral messenger RNA and, specifically, influenza virus transcriptase activity. Ribavirin appears to have multiple sites of action, and some of these (e.g., inhibition of GTP synthesis) may potentiate others (e.g., inhibition of GTP-dependent enzymes). 

Ribarvirin is a broad-spectmm antiviral agent that inhibits viral mRNA synthesis (Section 27.10). A step in the metabolic pathway responsible for the synthesis of guanosine triphosphate (GTP) converts inosine monophosphate (IMP) into xanthosine monophosphate (XMP). Ribarvirin is a competitive inhibitor of the enzyme that catalyzes that step. Thus, ribarvirin interferes with the synthesis of GTP and, therefore, with all nucleic acid synthesis. 

Subsequent developments suggested that the effects of muscarinic receptor stimulation are mediated by second messengers that are biosynthesized by at least two important events 1) inhibition of adenylyl cyclase, and 2) activation of phospholipase C. Both involve a guanosine triphosphate (GTP)-dependent mechanism. Two other important developments were the synthesis of radiolabeled muscarinic ligands and the utilization of molecular biology techniques in the study of muscarinic receptors. 

Ribavirin [13] is a guanosine analog that is intracellularly phosphorylated by the host cell s enzymes. Despite its mechanism is not yet fully elucidated, it apparently interferes with the synthesis of guanosine triphosphate to inhibit capping of viral mRNA and some viral RNA-dependent polymerases. Its triphosphate derivative inhibits the replication of a wide range of RNA and DNA viruses including influenza A and B, parainfluenza, respiratory syncytial virus (RSV), paramyxovirus, HCV and HIV-1. 

IMP is a common precursor to both adenine and guanine nucleotides. Adenylate (AMP) is biosynthesized from IMP in two steps by the substitution of an amino group for the carbonyl oxygen atom at C-6 (Figure 6.56). The addition of aspartate followed by the elimination of fumarate contributes the amino group. GTP (guanosine triphosphate) is the phosphoryl-group donor in the synthesis of the adenylosuccinate... 

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