Adenylate cyclase mechanism transfer

Hohmann AG, Suplita RL, Bolton NM, Neely MH, Fegley D, Mangieri R, Krey JF, Walker JM, Holmes PV, Crystal JD, Duranti A, Tontini A, Mor M, Tarzia G, Piomelli D (2005) An endocannabinoid mechanism for stress-induced analgesia. Nature 435(7045) 1108-12 Howlett AC, Qualy JM, Khachatrian LL (1986) Involvement of Gi in the inhibition of adenylate cyclase by cannabimimetic drugs. Mol Pharmacol 29(3) 307-13 Hsu K-T, Storch J (1996) Fatty acid transfer from liver and intestinal fatty acid-binding proteins to membranes occurs by different mechanisms. J Biol Chem 271(23) 13317—23... 

Using two enzymes, a mammalian adenylate cyclase and myosin ATPase, as examples the application of phosphorothioate analogues to the study of the mechanism of nucleotidyl and phosphoryl transfer will be described. 

The mono(ADP-ribosyl)ation, the transfer of the ADP-ribose moiety of NAD to a macromolecule, was discovered by Hayaishi et al. in 1968 as the mechanism of the cytotoxic effect of diphtheria toxin [1], The substrate of this toxin-catalyzed ADP-ribosylation is elongation factor-2. The same reaction is catal)Azed by Pseudomonas toxin. The second bacterial toxin involved in mono(ADP-ribosyl)ation of mammalian cell proteins is cholera toxin, the substrate of which was identified as the guanine nucleotide-binding regulatory component of membrane adenylate cyclase in 1978 [2].E. coli heat-labile enterotoxin is similar to cholera toxin in many respects. 

Sodium tungstate stimulates production of adenylate cyclase in ovarian homogenates. The activation is rapid and takes place also in brain, heart, lung, kidneys, and liver of the rat. Hwang and Ryan s explanation is based on a phosphate transfer mechanism [19]. 

Mechanisms of Renal Water Reabsorption - Much experimental evidence supports the hypothesis, first advanced by Orloff and Handler, that sodium transport and osmotic water flow that characterizes the physiological response to vasopressin.In a recent study. Chase and Aurbach have Identified two distinct adenyl cyclase systems located In renal membrane fractions of rats, one In the cortex and the other In the medulla.While the medullary enzyme was stimulated by vasopressin, cortex adenyl cyclase was more responsive to parathyroid hormone than vasopressin. The localization of parathyroid-sensitive adenyl cyclcise In renal cortex and vasopressin-sensitive adenyl cyclase in renal medulla appears to be consistent with reports that cellular transfer of calcium and phosphate occurs primarily in the proximal portions of the nephron, and sodium transport and water permeability are stimulated by vasopressin mainly In the collecting tubules. Vasopressin-Induced stimulation of adenyl cyclase In the cortex may reflect Its additional action on the distal tubule. 

---