Impaired glycolysis and protein catabolism induced by acid in L6 rat muscle cells.
BACKGROUND
In skeletal muscle, metabolic acidosis stimulates protein degradation and oxidation of branched-chain amino acids. This could occur to compensate for impairment of glucose utilization induced by acid.


METHODS
To test this hypothesis, glycolysis and protein degradation (release of [14C]-phenylalanine) were measured in L6 skeletal muscle cells cultured in Eagle's minimum essential medium at pH 7.1 or 7.5 for up to 3 days.


RESULTS
No marked changes in total DNA or in cell viability were detected, nor was there any significant effect on intracellular pH or the water content of the cells (which is thought to be a key regulator of protein turnover, especially in liver). In spite of this, acid stimulated protein degradation, induced net protein loss from the cultures, inhibited glucose uptake and glycolysis (lactate output) and was associated with increased [1-14C]-leucine oxidation. Effects on protein degradation and glycolysis were gradual, reaching a maximum after 20-30 h. To investigate whether glycolytic flux itself can influence protein degradation, increased glycolysis was simulated by adding glucose (20 mmol L-1) or pyruvate (1 mmol L-1) to the medium. At pH 7.1, neither addition had any effect on protein degradation.


CONCLUSIONS
Although acid-induced protein wasting is associated with impaired glycolysis, no obligatory coupling exists between glycolytic flux and protein degradation.
Bevington
A
A
Department of Nephrology, Leicester General Hospital, Leicester, UK.
Brown
J
J
Pratt
A
A
Messer
J
J
Walls
J
J
D000138:Acidosis / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D002470:Cell Survival; D006019:Glycolysis; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D051381:Rats
D000597:Amino Acids, Branched-Chain; D009124:Muscle Proteins