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Titolo:
Internal regulation of ATP turnover, glycolysis and oxidative phosphorylation in rat hepatocytes
Autore:
Ainscow, EK; Brand, MD;
Indirizzi:
Univ Cambridge, Dept Biochem, Cambridge CB2 1TN, England Univ Cambridge Cambridge England CB2 1TN hem, Cambridge CB2 1TN, England
Titolo Testata:
EUROPEAN JOURNAL OF BIOCHEMISTRY
fascicolo: 3, volume: 266, anno: 1999,
pagine: 737 - 749
SICI:
0014-2956(199912)266:3<737:IROATG>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
METABOLIC CONTROL ANALYSIS; TOP-DOWN APPROACH; POTATO-TUBER MITOCHONDRIA; CONTROL COEFFICIENTS; ENERGY-METABOLISM; STEADY-STATE; LIVER-MITOCHONDRIA; SACCHAROMYCES-CEREVISIAE; GLYCOGEN-PHOSPHORYLASE; PROTON LEAK;
Keywords:
control analysis; glycolysis; oxidative phosphorylation; ATP turnover; hepatocyte metabolism;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
79
Recensione:
Indirizzi per estratti:
Indirizzo: Brand, MD MRC, Dunn Human Nutr Unit, Wellcome Trust MRC Bldg,Hills Rd, Cambridge CB22XY, England MRC Wellcome Trust MRC Bldg,Hills Rd Cambridge England CB2 2XY
Citazione:
E.K. Ainscow e M.D. Brand, "Internal regulation of ATP turnover, glycolysis and oxidative phosphorylation in rat hepatocytes", EUR J BIOCH, 266(3), 1999, pp. 737-749

Abstract

Previously [Ainscow, E.K. & Brand, M.D. (1999) fur: J. Biochem. 263, 671-685], top-down control analysis was used to describe the control pattern of energy metabolism in rat hepatocytes. The system was divided into nine reaction blocks (glycogen breakdown, glucose release, glycolysis, lactate production, NADH oxidation, pyruvate oxidation, mitochondrial proton leak, mitochondrial phosphorylation and ATP consumption) linked by five intermediates (intracellular glucose B-phosphate, pyruvate and ATP levels, cytoplasmic NADH/NAD ratio and mitochondrial membrane potential). The kinetic responses (elasticities) of reaction blocks to intermediates were determined and used to calculate control coefficients. In the present paper, these elasticitiesand control coefficients are used to quantify the internal regulatory pathways within the cell. Flux control coefficients were partitioned to give partial flux control coefficients. These describe how strongly one block of reactions controls the flux through another via its effects on the concentration of a particular intermediate. Most flux control coefficients were the sum of positive and negative partial effects acting through different intermediates; these partial effects could be large compared to the final control strength. An important result was the breakdown of the way ATP consumption controlled respiration: changes in ATP level were more important than changes in mitochondrial membrane potential in stimulating oxygen consumption when ATP consumption increased. The partial internal response coefficients to changes in each intermediate were also calculated; they describe how steady state concentrations of intermediates are maintained. Increases in mitochondrial membrane potential were opposed mostly by decreased supply, whereas increases in glucose-6-phosphate, NADH/NAD and pyruvate were opposed mostly by increased consumption. Increases in ATP were opposed significantly by both decreased supply and increased consumption.

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Documento generato il 27/10/20 alle ore 04:24:15