Stimulation of glycolysis by histidine buffers in mammalian liver during cold hypoxia.
This study was designed to address the reasons why glycolysis in mammalian liver is unable to function more efficiently during periods of cold hypoxia. Our hypothesis was that control of intracellular pH, by use of amino acid buffers with high pKa values, would allow prolonged flux through glycolysis and better maintenance of liver high-energy adenine nucleotide pool. The effects of two concentrations of histidine (90 and 180 mM) and one of carnosine (90 mM), a histidyl dipeptide, on energy metabolism and levels of glycolytic substrate (glucose) and anaerobic endproduct (lactate) were investigated during cold hypoxia using rat livers to model the mammalian system. The transition to anaerobic metabolism was apparent by an immediate rise in lactate levels upon entry into cold hypoxia. By 10-14 h hypoxia, contents of the endproduct had increased by 10, 13.5, and 14.5 mumol/g in buffers containing 90 and 180 mM histidine and 90 mM carnosine, respectively. As well, ATP, total adenylate contents, and "energy charge" ratios exhibited a rapid decline from initial values of 2.3-3.3 mumol/g, 4.3-5.5 mumol/g, and 0.64-0.75, respectively, over the first 2-4 h of cold hypoxia. With respect to efficacy, the 180 mM histidine buffer exhibited the most positive maintenance of adenylate levels, followed closely by 90 mM carnosine, and finally 90 mM histidine as the least effective of the three buffers. Nevertheless, all three buffers examined in this study showed positive effects compared to similarly treated livers stored in a solution of minor buffering capacity (a citrate-based solution) over the same time period. The data support the hypothesis that glycolytic flux and cellular energetics can be maintained by the inclusion of efficient buffering agents during periods of cold hypoxia.
Churchill
T A
TA
University Department of Surgery, Royal Free Hospital School of Medicine, London, United Kingdom.
Green
C J
CJ
Fuller
B J
BJ
D000227:Adenine Nucleotides / Q000378:metabolism; D000693:Anaerobiosis / Q000187:drug effects; D000818:Animals; D002021:Buffers; D002336:Carnosine / Q000494:pharmacology; D003080:Cold Temperature; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006639:Histidine / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D051381:Rats
D000227:Adenine Nucleotides; D002021:Buffers; D007773:Lactates; D019344:Lactic Acid; D006639:Histidine; D002336:Carnosine; D005947:Glucose