The influence of hypoxia and anoxia on distribution of adenine nucleotides in isolated hepatocytes.
Isolated hepatocytes incubated under conditions of "chemical hypoxia" (KCN + iodoacetic acid) exhibited a marked dephosphorylation of the cytoplasmic and mitochondrial adenine nucleotides to AMP. Cytoplasmic adenine nucleotide levels (ATP + ADP + AMP) were decreased by 40%. There was no significant change in the mitochondrial adenine nucleotide pool size. For starved rats, but not for fed rats, addition of KCN to isolated hepatocytes resulted in a shift of the mitochondrial adenine nucleotide species to AMP. This difference was correlated with the maintenance of a substantial level of cytoplasmic ATP in the fed vs starved condition. The addition of fructose (but not glucose) to hepatocytes isolated from a starved rat, prevented the KCN-induced dephosphorylation of mitochondrial adenine nucleotides to AMP. Fructose-treated cells had a significant level of ATP in the cytoplasm, whereas glucose-treated cells did not. Addition of A23187 to fructose-treated (but not glucose-treated) cells resulted in a net loss in the mitochondrial adenine nucleotide content. The results suggest that the shift of matrix adenine nucleotides from ATP and ADP to AMP preserves the mitochondrial adenine nucleotide pool size during transient hypoxia by preventing net adenine nucleotide transport to the cytoplasm via the ATP-Mg/Pi carrier. This effectively protects those adenine nucleotides from the cytoplasmic purine degradation pathway, a strategy that has the potential to facilitate rapid recovery of bioenergetic status by oxidative phosphorylation upon reoxygenation.
Dransfield
D T
DT
Department of Biology, Tufts University, Medford, Massachusetts 02155.
Aprille
J R
JR
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008099:Liver / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000227:Adenine Nucleotides; D007461:Iodoacetates; D005632:Fructose; D000226:Mitochondrial ADP, ATP Translocases; D005947:Glucose; D011190:Potassium Cyanide; D019807:Iodoacetic Acid