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Titolo:
Top-down control analysis of ATP turnover, glycolysis and oxidative phosphorylation in rat hepatocytes
Autore:
Ainscow, EK; Brand, MD;
Indirizzi:
Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England Univ Cambridge Cambridge England CB2 1QW hem, Cambridge CB2 1QW, England
Titolo Testata:
EUROPEAN JOURNAL OF BIOCHEMISTRY
fascicolo: 3, volume: 263, anno: 1999,
pagine: 671 - 685
SICI:
0014-2956(199908)263:3<671:TCAOAT>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
METABOLIC CONTROL ANALYSIS; PROTON LEAK; MAMMALIAN-CELLS; LIVER CELLS; RESPIRATION; MITOCHONDRIA; SYSTEMS; GLUCOSE; CONDUCTANCE; CYCLES;
Keywords:
ATP turnover; control analysis; glycolysis; hepatocyte metabolism; oxidative phosphorylation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
59
Recensione:
Indirizzi per estratti:
Indirizzo: Brand, MD Univ Cambridge, Dept Biochem, Tennis Court Rd, Cambridge CB2 1QW, England Univ Cambridge Tennis Court Rd Cambridge England CB2 1QW ngland
Citazione:
E.K. Ainscow e M.D. Brand, "Top-down control analysis of ATP turnover, glycolysis and oxidative phosphorylation in rat hepatocytes", EUR J BIOCH, 263(3), 1999, pp. 671-685

Abstract

Control analysis was used to analyse the internal control of rat hepatocyte metabolism. The reactions of the cell were grouped into nine metabolic blocks linked by five key intermediates. The blocks were glycogen breakdown, glucose release, glycolysis, lactate production, NADH oxidation, pyruvate oxidation, mitochondrial proton leak, mitochondrial phosphorylation and ATP consumption. The linking intermediates were intracellular glucose-6-phosphate, pyruvate and ATP levels, cytoplasmic NADH/NAD ratio and mitochondrial membrane potential. The steady-state fluxes through the blocks and the levels of the intermediates were measured in the absence and presence of specific effecters of hepatocyte metabolism. Application of the multiple modulation approach gave the kinetic responses of each block to each intermediate (the elasticities). These were then used to calculate all of the control coefficients, which describe the degree of control each block had over the level of each intermediate, and over the rate of each process. Within this fulldescription of control, many different interactions could be identified. One key finding was that the processes that consumed ATP had only 35% of thecontrol over the rate of ATP consumption. Instead, the reactions that produced ATP exerted the most control over ATP consumption rate; particularly important were mitochondrial phosphorylation (30% of control) and glycolysis(19%). The rate of glycolysis was positively controlled by the glycolytic enzymes themselves (66% of control) and by ATP consumption (47%). Mitochondrial production of ATP, including oxidative, proton leak and phosphorylation processes, had negative control over glycolysis (-26%; the Pasteur effect). In contrast, glycolysis had little control over the rate of ATP production by the mitochondria (-10%; the Crabtree effect). Control over the flux through the mitochondrial phosphorylation block was shared between pyruvate oxidation (23%), ATP consumption (28%) and the mitochondrial phosphorylation block itself (64%).

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 00:10:13