Ischemic nucleotide breakdown increases during cardiac development due to drop in adenosine anabolism/catabolism ratio.
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.
de Jong
J W
JW
Cardiochemical Laboratory, Erasmus University Rotterdam, The Netherlands.
Keijzer
E
E
Huizer
T
T
Schoutsen
B
B
D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism; D000248:Adenosine Kinase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D003327:Coronary Disease / Q000378:metabolism*; D006321:Heart / Q000254:growth & development; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism*; D010430:Pentosyltransferases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014968:Xanthine Dehydrogenase / Q000378:metabolism
D009711:Nucleotides; D014968:Xanthine Dehydrogenase; D010430:Pentosyltransferases; C067995:nucleoside phosphorylase; D000248:Adenosine Kinase; D000243:Adenosine Deaminase; D000241:Adenosine