Effects of fructose on the energy metabolism and acid-base status of the perfused starved-rat liver. A 31 phosphorus nuclear magnetic resonance study

Abstract

Fructose metabolism has been studied with 31P n.m.r. in perfused livers from rats starved for 48h. The time course of changes in liver ATP, Pi and sugar phosphate (fructose l-phosphate) concentrations, and intracellular pH were followed in each perfusion after infusion of fructose to give an initial concentration of either 5mM or 10mM. Rapid falls in the concentrations of ATP and Pi and intracellular pH occurred after infusion of fructose, reaching a minimum after 4-5 min, which was lower in the 10mM group than in the 5mM group. These changes were accompanied by a rapid rise in fructose 1-phosphate, reaching a plateau also after 4-5 min. At both concentrations of fructose, after the early falls, some recovery of ATP, Pi and intracellular pH occurred; this was complete for Pi and intracellular pH in the 5mM-fructose experiments (within 12-30 min). Complete restoration of ATP to the pre-fructose value was not achieved in either the 5mM of 10mM groups. Measurements of the uptake of lactate by the liver indicated that the fall in intracellular pH was caused primarily by production of protons accompanying the formation of lactate from fructose with possibly a transient contribution generated during the rise in fructose 1-phosphate.

Effect of cyclosporine on hepatic energy status and on fructose metabolism after portacaval shunt in dog as monitored by phosphorus-31 nuclear magnetic resonance spectroscopy in vivo,

“…After the fructose challenge, the pH i fell from a value of approximately 7.3 to 7.0 (p < 0.01) in all three animal groups within 12 min and returned to a value close to baseline values thereafter (results not shown), confirming the findings of an earlier study performed in rat liver (28). Forty minutes after the fructose challenge, the pH i of the PCS-plus-CsA-treated dogs was not significantly different from that noted before the challenge.…”

“…This may reflect the fact that intracellular levels of the Pi that inhibits AMP degradation (32) are better preserved. Also, it is interesting that the changes for pH i noted in this study are consistent with data obtained using the perfused rat liver (28), suggesting that the fall in pH i after fructose is caused mainly by production of hydrogen ions accompanying the formation of lactate from fructose.…”

Molecular mechanisms of SR 4233-induced hepatocyte toxicity under aerobic versus hypoxic conditions

“…However as shown in Table IV, SR 4233 reduction by hepatocytes was not affected. As fructose markedly induces glycolysis and acidosis in hypoxic hepatocytes (Seglen, 1974) or perfused liver (Iles et al, 1980) and as an acidotic pH protects against hypoxic hepatocyte injury (Gores et al, 1989), the protective effect of acidosis against SR 4233 cytotoxicity was investigated. As shown in Table IV monensin, an agent which catalyses the exchange of Na+ for H+ and equalises intracellular pH to that of extracellular pH (Gores et al, 1989), prevented fructose protection.…”

“…Other investigators have shown that fructose markedly increased the anaerobic production of lactic acid particularly in hypoxic hepatocytes (Seglen, 1974), the classical Pasteur effect, and that significant acidosis developed (Iles et al, 1980). Furthermore acidosis protects against hypoxic injury in hepatocytes (Gores et al, 1989).…”

Hepatic intralobular mapping of fructose metabolism in the rat liver

“…Addition of fructose to rat liver perfusions causes an immediate but temporary decrease in hepatic ATP and P i , partly attributable to the accumulation of fructose 1-phosphate by the action of fructokinase (EC 2.7.1.4), degradation of adenine nucleotides to IMP and urate [1,2] and a simultaneous fall in hepatocyte intracellular pH (pH i ) [3]. Recovery of ATP is rapid but only partial, possibly because of irreversible degradation of adenine nucleotides.…”