Adenosine formation. Evidence for a direct biochemical link with energy metabolism

Abstract

The increase in tissue and coronary effluent adenosine concentration in hearts undergoing net ATP breakdown results from an accelation of adenosine formation and not from an inhibition of adenosine inactivation. Adenosine formation takes place inside intact isolated cells by a pathway distinct from the cell membrane 5'-nucleotidase, which hydrolyzes only extracellular AMP. Both the magnitude and the variation in the rate of adenosine formation in polymorphonuclear leukocytes undergoing ATP catabolism can be accounted for by the properties of a cytosolic 5'-nucleotidase that is also present in heart. This enzyme, which is allosterically activated by ATP-Mg and inhibited by Pi, provides a direct biochemical link between the energy status of the cell and the rate of adenosine formation. The actions of adenosine to dilate coronary arterioles, antagonize the inotropic effect of catecholamines, and reduce sympathetic-nerve firing would ameliorate the original energy imbalance. Adenosine may therefore function in heart and also in brain, skeletal muscle, kidney, and adipose tissue as a "retaliatory metabolite" that protects the cell against excessive external stimulation.