Guanosine triphosphate, formation

Receptors linked to guanylyl cyclase and which catalyze the formation of guanosine triphosphate (GMP) to guanosine-3A -cychc monophosphate (cychc GMP) include those for atrial natriuretic factor (ANF) and endothehal-derived relaxing factor (EDRF), mediating vasodilatation, and nitric oxide [10102 3-9], NO, or a clearly related derivative. 

These organisms have been used frequently in the elucidation of the biosynthetic pathway (37,38). The mechanism of riboflavin biosynthesis has formally been deduced from data derived from several experiments involving a variety of organisms (Fig. 5). Included are conversion of a purine such as guanosine triphosphate (GTP) to 6,7-dimethyl-8-D-ribityUuma2ine (16) (39), and the conversion of (16) to (1). This concept of the biochemical formation of riboflavin was verified in vitro under nonen2ymatic conditions (40) (see Microbial transformations). 

Guanylyl cyclases (GC) are a family of enzymes (EC 4.6.1.2) that catalyse the formation of the second messenger cyclic GMP (cGMP) from guanosine triphosphate (GTP). GCs are subdivided in soluble GCs and GCs that are membrane-bound and linked to a receptor. Activation occurs by nitric oxide (NO) and pqrtide hormones, respectively [1,2]. 

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). 

This subsequent splitting of succinyl-CoA releasing CoA and succinic acid is used to drive a substrate level phosphorylation reaction, but this time it results in the formation, not of ATP but of another nucleoside triphosphate, guanosine triphosphate (GTP) from GDP. GTP can of course be utilized by the cell in exactly the same way as ATP, and can be converted to ATP directly at the expense of ADP, as shown below. 

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. 

Interest in paclitaxel was stimulated by the finding that the drug possessed the unique ability to promote microtubule formation at cold temperatures and in the absence of guanosine triphosphate (GTP). It binds specifically to the P-tubulin subunit of microtubules and antagonizes the disassembly of this key cytoskeletal protein, with the result that bundles of microtubules and aberrant structures derived from microtubules appear in the mitotic phase of the cell cycle. Arrest in mitosis follows. Cell killing (CK) is dependent on both drug concentration and duration of cell exposure. 

Fig. 76.2 Polyphenols and polyphenol-rich sources induce endothelial-dependent NO- and EDH-mediated relaxations. Polyphenols are potent inducers of the oidothelial formation of nitric oxide (NO) and endothelium-derived hyperpolarizatitm (EDH) via a redox-soisitive mechanism. SKca small conductance calcium-activated potassium channels, IKca intermediate conductance calcium-activated potassium channels, Src Src family kinase, PI3K phosphatidylinositol 3-kinase, eNOS endothelial NO synthase, L-Arg L-arginine, sGC soluble guanylyl cyclase, GTP guanosine triphosphate, cGMP cyclic guanosine monophosphate, AA arachidonic acid, COX cyclooxygenase, ATP adenosine triphosphate, cAMP cyclic adenosine monophosphate...

Shorey, R. L., Ravel, J. M., Garner, C. W. and Shive, W. (1969) Formation and properties of the aminoacyl transfer ribonucleic acid-guanosine triphosphate-protein complex. An intermediate in the binding of aminoacyl transfer ribonucleic acid to ribosomes. J. Biol. Chem. 244,4555-4564. 

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