Catabolism of adenine nucleotides and its relation with intracellular phosphorylated metabolite concentration during ethanol oxidation in perfused rat liver.
Ethanol-induced perturbations in the energy metabolism and in the catabolism of adenine nucleotides were investigated by 31P NMR spectroscopy and HPLC analyses in perfused rat liver. Ethanol oxidation reduced the redox potential of the hepatocyte, leading to an intracellular accumulation of sn-glycerol 3-phosphate. This accumulation, in turn, led to a cytosolic P(i) depletion with stoichiometric relationship close to 1/1 for an initial period of 2 min. The concentration of nucleoside 5'-triphosphates (83 +/- 4% of ATP) was decreased during ethanol oxidation, reaching about 66% of its control value [2.88 +/- 0.02 mumol.(g of liver wet wt)-1] at high ethanol doses (10 and 70 mM). The depletion of P(i) relieved the inhibition exerted by this compound on AMP deaminase, key enzyme in the catabolism of adenine nucleotides. The degradation of AMP was monitored by HPLC analyses of the adenine nucleosides and bases released in the effluents. Integration over time of the total release of these metabolites accounted for the depletion of ATP recorded in the same time by 31P NMR spectroscopy. This result suggests that ATP depletion occurring during ethanol oxidation originated from an enhanced degradation of adenine nucleotides. There was a strong linear correlation (r2 = 0.92) between cytosolic P(i) level and allantoin release rate during ethanol perfusion. Cytosolic P(i) and allantoin release exhibited biphasic behavior, the recovery toward the initial levels being related to the release of P(i) in the cytoplasm during the complete catabolism of adenine nucleotides. Finally, the depletion of P(i) affected the glycogenolysis pathway, with a maximal inhibition of ca. 19% of the initial level.
Masson
S
S
Centre de Résonance Magnétique Biologique et Médicale, Centre National de la Recherche Scientifique, Faculté de Médecine de la Timone, Marseille, France.
Desmoulin
F
F
Sciaky
M
M
Cozzone
P J
PJ
D000227:Adenine Nucleotides / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000481:Allantoin / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology; D005994:Glycerophosphates / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010084:Oxidation-Reduction; D010477:Perfusion; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
D000227:Adenine Nucleotides; D005994:Glycerophosphates; D000481:Allantoin; D000431:Ethanol; D000255:Adenosine Triphosphate; D006003:Glycogen; C029620:alpha-glycerophosphoric acid