Physiological modulators adenosine

A further possibility to modulate physiological adenosine or agonistic effects could be allosteric enhancement. Allosteric enhancers described so far enhance the binding of several agonists by up to two-fold so they bind more efficiently, and lower concentrations of the agonist are needed (Bruns et al., 1990). Some of the compounds are claimed to have analgesic properties (Baraldi, 1999) or reported to be active in neuropathic pain (Li et al., 2002). 

Aguayo, C., Flores, C., Parodi, J., Rojas, R., Mann, G.E., Pearson, J.D., and Sobrevia, L. (2001) Modulation of adenosine transport by insulin in human umbilical artery smooth muscle ceUs from normal or gestational diabetic pregnancies. The Journal of Physiology, 534 (Pt 1), 243-254. 

The reaction is essentially irreversible under physiological conditions and is a major regulatory step of glycolysis. PFK-1 is an inducible, highly regulated, allosteric enzyme. In its active form, muscle PFK-1 is a homotetramer (M.W. 320,000) that requires K+ or NH4, the latter of which lowers Km for both substrates. When adenosine triphosphate (ATP) levels are low during very active muscle contraction, PFK activity is modulated positively despite low concentration of fructose-6-phosphate. Allosteric activators of muscle PFK-1 include adenosine monophosphate (AMP), adenosine diphosphate (ADP), fructose-6-phosphate, and inorganic phosphate (Pi) inactivators are citrate, fatty acids, and ATP. 

G. Marone, M. Valentine, and L.M. Lichtenstein, Modulation of cyclic AMP in human leukocytes by physiological doses of adenosine, Fed. Proc. 37 1688 (1978). 

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