Guanosine triphosphate phosphorylation

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... 

The subsequent cleavage of the thio-ester succinylCoA into succinate and coenzyme A by succinic acid-CoA ligase (succinyl CoA synthetase, succinic thiokinase) is strongly exergonic and is used to synthesize a phosphoric acid anhydride bond ( substrate level phosphorylation , see p. 124). However, it is not ATP that is produced here as is otherwise usually the case, but instead guanosine triphosphate (CTP). However, GTP can be converted into ATP by a nucleoside diphosphate kinase (not shown). 

Key Words Guanosine-5 -0-(3-thio)triphosphate phosphorylation serotonin (5-hydroxytryptamine) G protein kinase receptor calmodulin phospholipase. 

A protein that polymerizes to form microtubules. Tubulin is a target for anticancer therapy. See Feit, H Slusarek, L., and Shelanski, M.L., Heterogeneity of tubulin subunits, Proc. Natl. Acad. Sci. USA 68, 2028-2031, 1971 Fine, R.E., Heterogeneity of tubulin, Nat. New Biol. 233, 283-284, 1971 Rappaport, L., Leterrier, J.F., and Nunez, J., Non phosphorylation in vitro of 6 S tubulin from brain and thyroid tissue, FEBS Lett. 26, 239-352, 1972 Berry, R.W. and Shelanski, M.L., Interactions of tubulin with vinblastine and guanosine triphosphate, J. Mol. Biol. 71,71-80,1972 Hemminki, K., Relative turnover of tubulin subunits in rat brain, Biochim. Biophys. Acta 310, 285-288,1973 Timasheff, S.N., Frigon, R.P., and Lee,... 

STEPS s-6 Hydrolysis and dehydrogenation of succinyl CoA. Succinyl CoA is hydrolyzed to succinate in step 5. The reaction is catalyzed by succinyl CoA synthetase and is coupled with phosphorylation of guanosine diphosphate (GDP) to give guanosine triphosphate (GTP). The overall transformation is similar to that of step 8 in glycolysis (Figure 29.4), in which a thiol ester is converted into an acyl phosphate and a phosphate group is then transferred to ADP. 

Some biosynthetic reactions are driven by the hydrolysis of nucleoside triphosphates that are analogous to ATP—namely, guanosine triphosphate (GTl ), uridine triphosphate (UTP), and cytidine triphosphate (CTP). The diphosphate forms of these nucleotides are denoted by GDP, UDP, and CDP, and the monophosphate forms are denoted by GMP, UMP, and CMP. Enzymes catalyze the transfer of the terminal phosphoryl group from one nucleotide to another. The phosphorylation of nucleoside monophosphates is catalyzed by a family of nucleoside monophosphate kinases, as discussed in Section 9.4. The phosphorylation of nucleoside diphosphates is catalyzed by 7iucleoside diphosphate kinase, an enzyme with broad... 

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. 

GDP, guanosine diphosphate, is converted to GTP, guanosine triphosphate, by a substrate level phosphorylation, and CoA-SH is released. GTP is a high-energy compound equivalent to and interchangeable with ATP. 

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