Ischemic nucleotide breakdown increases during cardiac development due to drop in adenosine anabolism/catabolism ratio

Abstract

Our earlier work on reperfusion showed that adult rat hearts released almost twice as much purine nucleosides and oxypurines as newborn hearts did [Am J Physiol 254 (1988) H1091]. A change in the ratio anabolism/catabolism of adenosine could be responsible for this effect. We therefore measured the activity of adenosine kinase, adenosine deaminase, nucleoside phosphorylase and xanthine oxidoreductase in homogenates of hearts and myocytes from neonatal and adult rats. In hearts the activity of adenosine deaminase and nucleoside phosphorylase (10-20 U/g protein) changed relatively little. However, adenosine kinase activity decreased from 1.3 to 0.6 U/g (P less than 0.025), and xanthine oxidoreductase activity increased from 0.02 to 0.85 U/g (P less than 0.005). Thus the ratio in activity of these rate-limiting enzymes for anabolism and catabolism dropped from 68 to 0.68 during cardiac development. In contrast, the ratio in myocytes remained unchanged (about 23). The large difference in adenosine anabolism/catabolism ratio, observed in heart homogenates, could explain why ATP breakdown due to hypoxia is lower in neonatal than in adult heart. Because this change is absent in myocytes, we speculate that mainly endothelial activities of adenosine kinase and xanthine oxidoreductase are responsible for this shift in purine metabolism during development.

Hyperthyroidism increases adenosine transport and metabolism in the rat heart

“…Furthermore, purine nucleoside phosphorylase activity, which is also located in the endothelium [35] tended to be more active following T 4 treatment. This may represent a growth response either in myocytes or in the endothelium in line with the observations of PNP activity in rat cardiomyocytes after one day of culture [32] despite the absence of activity in freshly isolated cells [21 ].…”

“…Decreases in enzyme activity in the hyperthyroid group are only observed in membrane 5'-nucleotidase and adenosine deaminase (Table 1), enzymes which are totally (M5'N) or partially (ADA) membrane-bound and predominantly located in the endothelium [32]. These changes may reflect an increase in the membrane/cell volume ratio, which is a characteristic feature of hypertrophy.…”

Accumulation of poly(ADP-ribose) polymerase inhibitors in children with chronic renal failure

“…This is a consequence of a higher rate of nucleotide turnover in a growing organism. Some other potential differences such as an increasing activity of xanthine oxidoreductase and aldehyde oxidase with age still need to be confirmed in humans [14]. Therefore it is important to find out whether nicotinamide metabolites accumulate in plasma of children with CRF and whether the pattern of this accumulation is similar to or different from adult patients [15].…”

Myocardial malondialdehyde and uric acid release after short-lasting coronary occlusions during coronary angioplasty: Potential mechanisms for free radical generation

“…19~29,30 Published data on xanthine oxidase in human myocardium are controversial,30 perhaps owing to the fact that the enzyme can inactivate itself. 31 We found urate production after angioplasty, l5 but not by isolated perfused human heart3u The parallel production of urate and malondialdehyde after repetitive coronary occlusions in the angioplastic procedure suggests the possible importance of this 394 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 68 AUGUST 1, 1991 pathway in the production of oxygen-free radicals in the human ischemic heart. These radicals may play a role in the persistence of regional left ventricle dysfunction after reperfusion.…”