Is the purine nucleotide cycle important in heart muscle?

Abstract

The purine nucleotide cycle catalyzes the net reaction: aspartate + GTP + H2O----fumarate + NH3 + GDP + Pi. The cycle leads to regeneration of AMP. In skeletal muscle the cycle's rate of operation increases severalfold in response to a corresponding increase in work load. This results in a net increase in citric-acid-cycle intermediates and in release of ammonia. The same may be expected in heart muscle, which, like skeletal muscle, possesses the enzymes of the purine nucleotide cycle. Isolated and working rat hearts were therefore perfused for 45 min at low or high work load (0.16 vs. 0.42 kg X m/min per g dry wt.) with glucose (5 mM) as substrate. Release of ammonia into the perfusate as well as the content of citric-acid-cycle intermediates (citrate, isocitrate, 2-oxoglutarate, malate, and oxaloacetate), related amino acids (aspartate, glutamate, and glutamine), adenine nucleotides, and creatine phosphate were measured in freeze-clamped tissue. There was no significant change between low and high work load in the sum of the citric-acid-cycle intermediates (1.295 vs. 1.313 mumole/g dry wt.), in aspartate (13.21 vs. 14.32 mumole/g dry wt.), in glutamate (15.58 vs. 15.67 mumole/g dry wt.), ATP (19.06 vs. 19.17 mumole/g dry wt.), ADP (5.00 vs. 4.11 mumole/g dry wt.), AMP (1.45 vs. 1.00 mumole/g dry wt.) or in creatine phosphate (22.58 vs. 25.80 mumole/g dry wt.). Ammonia release was 26 and 22 mumole/hr per g dry wt. at low and high work load, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)