Document Detail


Stimulation of glycolysis by histidine buffers in mammalian liver during cold hypoxia.
MedLine Citation:
PMID:  7793983     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
T A Churchill; C J Green; B J Fuller
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  320     ISSN:  0003-9861     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  1995 Jun 
Date Detail:
Created Date:  1995-07-27     Completed Date:  1995-07-27     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  43-50     Citation Subset:  IM    
Affiliation:
University Department of Surgery, Royal Free Hospital School of Medicine, London, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Adenine Nucleotides / metabolism
Anaerobiosis / drug effects
Animals
Anoxia / metabolism
Buffers
Carnosine / pharmacology
Cold Temperature
Energy Metabolism / drug effects
Glucose / metabolism
Glycolysis / drug effects*
Histidine / pharmacology*
Kinetics
Lactates / metabolism
Lactic Acid
Liver / drug effects*,  metabolism*
Male
Models, Biological
Rats
Chemical
Reg. No./Substance:
0/Adenine Nucleotides; 0/Buffers; 0/Lactates; 305-84-0/Carnosine; 50-21-5/Lactic Acid; 50-99-7/Glucose; 71-00-1/Histidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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