GDP/GTP cycle

The GDP/GTP cycle of heterotrimeric G proteins is shown in Fig. 3.12. Heterotrimeric G proteins hydrolyse GTP at rates 1000 times (or more) faster than Ras. 

Rab proteins exist in all cells and form the largest branch of the Ras superfamily. This family performs a central function in vesicular transport. Rab proteins influence and regulate the budding, targeting, docking and fusion of vesicles as well as processes of exocytosis and endocytosis involving clathrin-coated vesicles. During these functions, Rab proteins cycle between the cytosol and the cell membrane, and this cyle is superimposed on a GDP/GTP cycle. The cytosolic pool of the Rab pro-... 

Tryptophan Fluorescence Measurements of the GDP/GTP Cycle of the Small G Protein Arf and Sar... 

Stimulation and inhibition of the enzyme by the GPCR-G-protein cycle occur by analogous mechanisms. Agonists induce hormone receptors to increase a Ga-GDP-GTP exchange and subsequent Ga 3y dissociation (GDP-a py + GTP GTP-ax + [3y + GDP) (Fig. 4). Consequently, agents that affect either the dissociation of either G or Gs, or the association of their respective as, a , or (3y subunits with adenylyl cyclase could affect rates of cAMP formation in enzyme preparations or in intact cells and tissues. There are several important examples. Gas is stably activated by poorly hydrolyzable analogs of GTP, e.g. GTPyS... 

Panniers, R., and Henshaw, E. C. (1983). A GDP/GTP exchange factor essential for eukaryotic initiation factor 2 cycling in Ehrlich ascites tumor cells and its regulation by eukaryotic initiation factor 2 phosphorylation. J. Biol. Chem. 258, 7928—7934. 

TCA cycle Oxidation of isocitrate, a-ketoglutarate, and malate Oxidation of succinate GDP GTP +6 +2 +2... 

Figure 23-43 The light-activated transducin cycle. In step a photoexcited rhodopsin (R ) binds the GDP complex of the heterotrimeric transducin (T ). After GDP—GTP exchange (step b) the activated transducin T GTP reacts with the inhibited phosphodiesterase (PDEapY2) to release the activated phosphodiesterase (PDEap). Based on scheme by Stryer528 and other information.

The oligomeric structure of the heterotrimeric G proteins increases the complexity and diversity of their signaling mechanisms. The intrinsic GTP cycle is direcdy associated with a cycle of subunit dissociation in which the oc subunit (which contains the nucleotide-binding site) can dissociate from a stable fiy dimer (Fig. 1). In the inactive GDP-bound state, high affinity between the oc and /fy subunits favors association. When GTP is bound, the affinity between subunits is lowered and dissociation is promoted. This allows both oc and fty subunits to act as coordinate or diverse regulators of downstream targets. Reassociation of the subunits inhibits downstream... 

FBS FGF FITC GO-phase G1-phase G2-phase GMP, GDP, GTP foetal bovine serum fibroblast growth factor fluoroscein isothiocyanate the resting stage of the cell cycle the first gap in the cell cycle (between M and S) the second gap in the cell cycle (between S and M) guanosine monophosphate, diphosphate, triphosphate... 

Fig. 1. ADP-ribosylafion of Rho by C3 transferases. Rho proteins are regulated by a GTPase cycle. The GTP-binding proteins ore inactive with GDP bound, and active in the GTP-bound form. GDP/GTP exchange is facilitated by guanine nucleotide dissociation stimulator(s) (GDS) and inhibited by guanine nucleotide dissociation inhibitor(s) (GDI). In the active form, Rho protein interacts with its effector(s) and induces several cellular responses, one of which is polymerization of actin. Rho is ADP-ribosylated by C3 transferases at asparagine-41. Most likely, the modification inhibits the interaction of Rho with its effector(s) which results in inhibition of Rho dependent processes (e.g. F-actin depolymerization)...

One further important detail of the TCA cycle is that, as well as making CO2 and a lot of reducing power as NADH and FADH2, it also in effect produces one molecule of ATP directly. One of the cycle s reactions converts GDP and phosphate into GTP. GDP/GTP are chemically very similar to ADP/ATP, and in energy terms GTP and ATP are equivalent, much like, say French euros and German euros. There is an enzyme that will bring about that equivalence, converting GTP plus ADP into GDP plus ATP. 

Ras is a G protein that cycle between two conformations, an activated Ras-GTP or inactivated form Ras-GDP. Ras, attached to the cell membrane by lipidation, is a key component in many signalling cascades, which couple growth factor receptors to downstream effectors that control such processes as cytoskeletal integrity, proliferation, cell adhesion, apoptosis and cell migration. Mutations and dysregulations of the Ras protein leading to increased invasion and metastasis, and decreased apoptosis are very common in cancers. 

Succinyl-CoA is converted to succinate by the enzyme succinate thiokinase (succinyl-CoA synthetase). This is the only example in the citric acid cycle of substrate-level phosphorylation. Tissues in which glu-coneogenesis occurs (the hver and kidney) contain two isoenzymes of succinate thiokinase, one specific for GDP and the other for ADP. The GTP formed is used for the decarboxylation of oxaloacetate to phos-phoenolpymvate in gluconeogenesis and provides a regulatory hnk between citric acid cycle activity and the withdrawal of oxaloacetate for gluconeogenesis. Nongluconeogenic tissues have only the isoenzyme that uses ADP. 

The now deacylated tRNA is attached by its anticodon to the P site at one end and by the open GGA tail to an exit (E) site on the large ribosomal subunit (Figure 38-8). At this point, elongation factor 2 (EE2) binds to and displaces the peptidyl tRNA from the A site to the P site. In turn, the deacylated tRNA is on the E site, from which it leaves the ribosome. The EF2-GTP complex is hydrolyzed to EF2-GDP, effectively moving the mRNA forward by one codon and leaving the A site open for occupancy by another ternary complex of amino acid tRNA-EFlA-GTP and another cycle of elongation. 

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