TAILIEUCHUNG - Báo cáo khoa học: Mathematical modelling of the urea cycle A numerical investigation into substrate channelling

Metabolite channelling, the process in which consecutive enzymes have confined substrate transfer in metabolic pathways, has been proposed as a biochemical mechanism that has evolved because it enhances catalytic rates and protects unstable intermediates. Results from experiments on the synthesis of radioactive urea [Cheung, C., Cohen, . & Raijman, L (1989)J. Biol. , 4038–4044] have been interpreted as implying channelling of arginine between argininosuccinate lyase and arginase in permeabi-lized hepatocytes. . | Eur. J. Biochem. 270 3953-3961 2003 FEBS 2003 doi Mathematical modelling of the urea cycle A numerical investigation into substrate channelling Anthony D. Maher1 Philip W. Kuchel1. Fernando Orteaa2 Pedro de Atauri2 Josep Centelles2 and Marta Cascante2 1 School of Molecular and Microbial Biosciences University of Sydney Australia department de Bioquimica i Biologia Molecular Universitat de Barcelona Spain Metabolite channelling the process in which consecutive enzymes have confined substrate transfer in metabolic pathways has been proposed as a biochemical mechanism that has evolved because it enhances catalytic rates and protects unstable intermediates. Results from experiments on the synthesis of radioactive urea Cheung C. Cohen . Raijman L 1989 J. Biol. Chem. 264 4038-4044 have been interpreted as implying channelling of arginine between argininosuccinate lyase and arginase in permeabi-lized hepatocytes. To investigate this interpretation further a mathematical model of the urea cycle was written using Mathematica it simulates time courses of the reactions. The model includes all relevant intermediates peripheral metabolites and subcellular compartmentalization. Analysis of the output from the simulations supports the argument for a high degree of but not absolute channelling and offers insights for future experiments that could shed more light on the quantitative aspects of this phenomenon in the urea cycle and other pathways. Keywords arginase mathematical modeling metabolite channeling urea cycle. There has been considerable debate in recent years over the phenomenon of metabolite channelling 1-3 . Channelling has been defined as the process by which two or more sequential enzymes in a pathway interact to transfer an intermediate from one active site to another without allowing free diffusion into the bulk system 4 . It has been suggested that channelling plays a fundamental role in regulation of certain reaction schemes and

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