tailieunhanh - Báo cáo khoa học: Pyruvate metabolism in rat liver mitochondria What is optimized at steady state?

A representative model of mitochondrial pyruvate metabolism was broken down into its extremal independent currents and compared with experimen-tal data obtained from liver mitochondria incubated with pyruvate as a substrate but in the absence of added adenosine diphosphate. | iFEBS Journal Pyruvate metabolism in rat liver mitochondria What is optimized at steady state Jorg W. Stucki and Robert Urbanczik Department of Pharmacology University of Bern Switzerland Keywords dominant reactions mitochondria optimization of metabolism pyruvate metabolism stoichiometric network analysis Correspondence J. W. Stucki Department of Pharmacology University of Bern Friedbuhlstrasse 49 CH-3010 Bern Switzerland Fax 41 31 632 4992 Tel 41 31 632 3281 E-mail Website http pki Received 17 August 2005 revised 28 September 2005 accepted 4 October 2005 doi A representative model of mitochondrial pyruvate metabolism was broken down into its extremal independent currents and compared with experimental data obtained from liver mitochondria incubated with pyruvate as a substrate but in the absence of added adenosine diphosphate. Assuming no regulation of enzymatic activities the free-flow prediction for the output of the model shows large discrepancies with the experimental data. To study the objective of the incubated mitochondria we calculate the conversion cone of the model which describes the possible input output behaviour of the network. We demonstrate the consistency of the experimental data with the model because all measured data are within this cone. Because they are close to the boundary of the cone we deduce that pyruvate is converted very efficiently 93 to produce the measured extramitochondrial metabolites. We find that the main function of the incubated mitochondria is the production of malate and citrate supporting the anaplerotic pathways in the cytosol notably gluconeogenesis and fatty acid synthesis. Finally we show that the major flow through the enzymatic steps of the mitochondrial pyruvate metabolism can be reliably predicted based on the stoichiometric model plus the measured extramitochondrial products. A major advantage of this method is that neither .