Evidence for a substrate cycle between AMP and adenosine in isolated hepatocytes.
The effect of adenosine on the metabolism of prelabeled adenine nucleotides was investigated in isolated hepatocytes. Adenosine caused an approximately equal to 2-fold increase in the ATP content of the cells. This effect was in part counteracted by an increased rate of adenine nucleotide catabolism that could be explained by a stimulation of both AMP deaminase (AMP aminohydrolase, EC 3.5.4.6) and the cytoplasmic 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) because of the increased concentration of ATP. The unexpected finding that labeled adenosine was formed immediately after the addition of the unlabeled nucleoside could be explained by the trapping effect of adenosine. An accumulation of labeled adenosine was observed also in the presence of 5-iodotubercidin, a potent inhibitor of adenosine kinase (ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20). Under these conditions, there was a decrease in the concentration of ATP in the cell and a 2- to 3-fold increase in the rate of formation of allantoin. This formation of adenosine was only slightly decreased by inhibition of the membranous 5'-nucleotidase; it led to the accumulation of S-adenosylhomocysteine in the presence of coformycin and an excess of L-homocysteine. It was concluded that, under basal conditions, the cytoplasmic 5'-nucleotidase present in the liver cell continuously produces adenosine, which is immediately reconverted into AMP by adenosine kinase, without giving rise to allantoin. This futile cycle between AMP and adenosine amounts to at least 20 nmol/min per g of liver and, thus, exceeds the basic rate of allantoin formation.
D000659:AMP Deaminase / Q000378:metabolism; D000227:Adenine Nucleotides / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D000248:Adenosine Kinase / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000818:Animals; D008099:Liver / Q000378:metabolism*; D009708:Nucleotidases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D051381:Rats; D012435:S-Adenosylhomocysteine / Q000378:metabolism
D000227:Adenine Nucleotides; D000249:Adenosine Monophosphate; D012435:S-Adenosylhomocysteine; D000248:Adenosine Kinase; D009708:Nucleotidases; D010744:Phosphoric Monoester Hydrolases; D000659:AMP Deaminase; D000241:Adenosine