Abnormalities in Initiation of G-Protein Signal

Two-well studied bacterial toxins, cholera toxin and pertussis toxin, perturb normal functioning of G proteins by ADP ribosylation of specific amino acid residues (discussed earlier). 

An example of decreased function due to impaired activation or loss of Gsa and resistance to hormone action is pseudohypoparathyroidism Albright s hereditary osteodystrophy). Patients with this syndrome exhibit generalized resistance to the action of those hormones dependent on Gsq, for their function despite elevated serum hormone levels. Several dysmorphic features are also characteristic of these patients. 

The calcium system is more complex than the cAMP system and contains a variety of mechanisms for transducing the Ca signal into changes in cellular function. It is also sensitive and responds to relatively small, transient changes in free Ca concentration. This sensitivity is desirable from a regulatory point of view, but it also 

The inner mitochondrial membrane may function primarily as a calcium sink, taking up excess calcium in the cytosol that results from hormonal activation of the cell. At cytosolic Ca + concentrations greater than 0.6 /rmol/L, the mitochondrial calcium pump is activated and stores calcium in the mitochondrial matrix as a nonionic, rapidly exchangeable, phosphate salt. At low cytosolic calcium concentrations, the inner mitochondrial membrane allows Ca + to leak into the cytosol. The capacity of the active influx pathway (the pump) is much greater than that of the passive efflux route (the leak). The mitochondrial pump-leak system may serve to fine-tune the cytosolic calcium concentration while the plasma membrane is the principal safeguard against entry of toxic amounts of calcium into the cell. 

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