TAILIEUCHUNG - Báo cáo khoa học: Adenine and adenosine salvage pathways in erythrocytes and the role of S-adenosylhomocysteine hydrolase A theoretical study using elementary flux modes Stefan Schuster and Dimitar Kenanov

This article is devoted to the study of redundancy and yield of salvage pathways in human erythrocytes. These cells are not able to synthesize ATPde novo. However, the salvage (recycling) of certain nucleosides or bases to give nucleotide triphosphates is operative. As the salvage pathways use enzymes consuming ATP as well as enzymes producing ATP, it is not easy to see whether a net synthesis of ATP is possible. As for pathways using adenosine, a straightforward assumption is that these pathways start with adenosine kinase | iFEBS Journal Adenine and adenosine salvage pathways in erythrocytes and the role of S-adenosylhomocysteine hydrolase A theoretical study using elementary flux modes Stefan Schuster and Dimitar Kenanov Department of Bioinformatics Friedrich Schiller University Jena Germany Keywords elementary flux modes enzyme deficiencies erythrocytes nucleotide metabolism salvage pathways Correspondence S. Schuster Department of Bioinformatics Friedrich Schiller University Ernst-Abbe-Platz 2 07743 Jena Germany Fax 49 3641 946452 Tel 49 3641 949580 E-mail schuster@ Received 6 June 2005 revised 5 August 2005 accepted 19 August 2005 doi This article is devoted to the study of redundancy and yield of salvage pathways in human erythrocytes. These cells are not able to synthesize ATP de novo. However the salvage recycling of certain nucleosides or bases to give nucleotide triphosphates is operative. As the salvage pathways use enzymes consuming ATP as well as enzymes producing ATP it is not easy to see whether a net synthesis of ATP is possible. As for pathways using adenosine a straightforward assumption is that these pathways start with adenosine kinase. However a pathway bypassing this enzyme and using S-adenosylhomocysteine hydrolase instead was reported. So far this route has not been analysed in detail. Using the concept of elementary flux modes we investigate theoretically which salvage pathways exist in erythrocytes which enzymes belong to each of these and what relative fluxes these enzymes carry. Here we compute the net overall stoichiometry of ATP build-up from the recycled substrates and show that the network has considerable redundancy. For example four different pathways of adenine salvage and 12 different pathways of adenosine salvage are obtained. They give different ATP glucose yields the highest being 3 10 for adenine salvage and 2 3 for adenosine salvage provided that adenosine is not used as an energy source. .

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