Guanosine triphosphate processes

G-Protein Coupling. The heterotrimeric guanosine triphosphate (GTP) binding proteins, known as G-proteins, are a principal family of proteins serving to couple membrane receptors of the G-protein family to ionic and biochemical processes. This topic is reviewed in References 63—67. 

The biosynthesis processes of purines, pterins, and flavins are closely related. Both pterins and flavins are synthesized via the guanosine triphosphate (GTP) purine intermediate. 

G proteins comprise several families of diverse cellular proteins that subserve an equally diverse array of cellular functions. These proteins derive their name from the fact that they bind the guanine nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP) and possess intrinsic GTPase activity. G proteins play a central role in signal transduction as well as in a myriad of cellular processes, including membrane vesicle transport,... 

The calcineurin inhibitors tacrolimus (FK 506) and cyclosporin A block the function of dynamin and are thought to be specific for clathrin-mediated uptake (50). The smal guanosine triphosphate (GTP)ase dynamin is also involved in other processes and is therefore described in section Dynamin Dependence on Liposome Uptake. ... 

Note that this overall reaction requires three coenzymes that we encountered as metabolites of vitamins in chapter 15 NAD+, derived from lucotiiuc acid or nicotinamide FAD, derived from riboflavin and coenzyme A(CoASH), derived from pantothenic acid. In the overall process, acetyl-SCoA is oxidized to two molecules of carbon dioxide with the release of CoASH. Both NAD+ and FAD are reduced to, respectively, NADH and FADH2. Note that one molecule of guanosine triphosphate, GTP, functionally equivalent to ATP, is generated in the process. 

G-Protein Coupling. The heterotrimenc guanosine triphosphate (GTP) binding proteins, known as G-proteins, are a principal family of proteins serving to couple membrane receptors of the G-protein family to ionic and biochemical processes. The G-proteins are heterotrimers made of three families of subunits, o,/3. and y, which can interact specifically with discrete regions on G-protein-coupied receptors. This includes most receptors for neurotransmitters and polypeptide hormones (see Neuroregulators), G-protein-eoupled receptors also embrace the odorant receptor family and the rhodopsin-linked visual cascade. 

Fig. 2.1. Examples from The Energy Hall of Fame. These molecules not only deliver energy, but transfer special groups in the process. Acyl, RCO— ADP, adenosine diphosphate ATP, adenosine triphosphate dUMP deoxyuridine monophosphate FAD, flavin adenine dinucleotide GTP, guanosine triphosphate NADH, nicotinamide adenine dinucleotide NADP, nicotinamide adenine dinucleotide phosphate P, phosphate TMP, thymidine monophosphate UDP, uridine diphosphate UTP, uridine triphosphate.

The muscarinic cholinergic system has quite a different mode of operation in that the receptor is connected to the final action by a chain of events. Thus its response is slower than the nicotinic, where the receptor and ion channel are closely connected. Five distinct muscarinic receptors have been identified in mammals, based on anatomical location, genetic analysis, function, and amino acid sequence. All of them have seven transmembrane domains [166, 167, 168, 169]. The N- terminal domain outside the cell binds acetylcholine or other ligands at a site that includes an aspartate residue, while the C-terminal domain inside the cell is coupled to a so-called G-protein , which is initially bound to guanosine diphosphate (GDP), but exchanges it for guanosine triphosphate (GTP) when activated by its transmitter. The activated G-protein then activates phospholipase C, which hydrolyzes phosphoinositides to release 1,4,5-inositol triphosphate [170]. The final action depends on which type of cell is involved so that in some types ion channels are opened just as with the nicotinic receptor, but in other cases other processes are affected, for example the release of dopamine [171]. Since there are these differences... 

The conversion of IMP to AMP requires amination at C-6 of the purine system, and the nitrogen for this process is derived from aspartate (Asp, D) (adenylosuccinate synthase, EC 6.3.4.4). It appears that the driving force for the loss of water in this process that yields N -l, 2-dicarboxyl adenosine monophosphate (adenosine 5 -phosphate, AMP) is the conversion of guanosine triphosphate (GTP) to guano-sine diphosphate (GDP). Adenosine monophosphate (adenosine 5 -phosphate, AMP) is formed from the N -derivative by loss of fumarate (catalyzed by adenylosuccinate lyase, EC 4.3.2.2). 

These oxidation reactions require oxygen (O2) and tetrahydrobiopterin as a cofactor. Thus, as shown in Scheme 13.39, 7,8-dihydroneopterin 3 -triphosphate (generated from guanosine triphosphate [GTP] as seen in Scheme 12.118) is converted to 6-pyruvoyl-5,6,7,8-tetrahydropterin by an elimination reaction and two keto-enol isomerizations. The process is catalyzed by the enzyme 6-pyruvoyltetra-hydropterin synthase (EC 4.2.3.12). Then, via an intermediate, written as an equilibrium between a-hydroxyketones (named dihydrosepiapterin) linked by a common enol, reduction to tetrahydrobiopterin is effected (in two separate steps) by 2 equivalents of NADPH used by the enzyme sepiapterin reductase (EC 1.1.1.153). Tetrahydrobiopterin is the cofactor involved in the National Institutes of Health (NIH) shift (cf. Chapter 6) pathway used by the iron-containing enzyme phenylalanine 4-monooxygenase (EC 1.14.16.1) to convert phenylalanine (Phe, F) to tyrosine (Tyr, Y) and is converted to (6i )-6-(L-erythro-l,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin in the process. 

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