A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks

被引:652
作者
Schuster, S [1 ]
Fell, DA
Dandekar, T
机构
[1] Max Delbruck Ctr Mol Med, Dept Bioinformat, D-13092 Berlin, Germany
[2] Oxford Brookes Univ, Sch Biol & Mol Sci, Oxford OX3 0BP, England
[3] European Mol Biol Lab, Biocomp & Struct Program, D-69012 Heidelberg, Germany
关键词
elementary modes; metabolic networks; functional genomics; stochiometric network analysis;
D O I
10.1038/73786
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
A set of linear pathways often does not capture the full range of behaviors of a metabolic network. The concept of 'elementary flux modes' provides a mathematical tool to define and comprehensively describe all metabolic routes that are both stoichiometrically and thermodynamically feasible for a group of enzymes. We have used this concept to analyze the interplay between the pentose phosphate pathway (PPP) and glycolysis. The set of elementary modes for this system involves conventional glycolysis, a futile cycle, all the modes of PPP function described in biochemistry textbooks, and additional modes that are a priori equally entitled to pathway status. Applications include maximizing product yield in amino acid and antibiotic synthesis, reconstruction and consistency checks of metabolism from genome data, analysis of enzyme deficiencies, and drug target identification in metabolic networks.
引用
收藏
页码:326 / 332
页数:7
相关论文
共 46 条
[1]   Glycolysis in bloodstream form Trypanosoma brucei can be understood in terms of the kinetics of the glycolytic enzymes [J].
Bakker, BM ;
Michels, PAM ;
Opperdoes, FR ;
Westerhoff, HV .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (06) :3207-3215
[2]   Flux analysis of underdetermined metabolic networks: The quest for the missing constraints [J].
Bonarius, HPJ ;
Schmid, G ;
Tramper, J .
TRENDS IN BIOTECHNOLOGY, 1997, 15 (08) :308-314
[3]  
Bonarius HPJ, 1996, BIOTECHNOL BIOENG, V50, P299, DOI 10.1002/(SICI)1097-0290(19960505)50:3<299::AID-BIT9>3.0.CO
[4]  
2-B
[5]   Predicting function: From genes to genomes and back [J].
Bork, P ;
Dandekar, T ;
Diaz-Lazcoz, Y ;
Eisenhaber, F ;
Huynen, M ;
Yuan, YP .
JOURNAL OF MOLECULAR BIOLOGY, 1998, 283 (04) :707-725
[6]   Nonoxidative pentose phosphate pathways and their direct role in ribose synthesis in tumors: is cancer a disease of cellular glucose metabolism? [J].
Boros, LG ;
Lee, PWN ;
Brandes, JL ;
Cascante, M ;
Muscarella, P ;
Schirmer, WJ ;
Melvin, WS ;
Ellison, EC .
MEDICAL HYPOTHESES, 1998, 50 (01) :55-59
[7]   COMPLETE SET OF STEADY-STATES FOR THE GENERAL STOICHIOMETRIC DYNAMICAL SYSTEM [J].
CLARKE, BL .
JOURNAL OF CHEMICAL PHYSICS, 1981, 75 (10) :4970-4979
[8]   Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence [J].
Cole, ST ;
Brosch, R ;
Parkhill, J ;
Garnier, T ;
Churcher, C ;
Harris, D ;
Gordon, SV ;
Eiglmeier, K ;
Gas, S ;
Barry, CE ;
Tekaia, F ;
Badcock, K ;
Basham, D ;
Brown, D ;
Chillingworth, T ;
Connor, R ;
Davies, R ;
Devlin, K ;
Feltwell, T ;
Gentles, S ;
Hamlin, N ;
Holroyd, S ;
Hornby, T ;
Jagels, K ;
Krogh, A ;
McLean, J ;
Moule, S ;
Murphy, L ;
Oliver, K ;
Osborne, J ;
Quail, MA ;
Rajandream, MA ;
Rogers, J ;
Rutter, S ;
Seeger, K ;
Skelton, J ;
Squares, R ;
Squares, S ;
Sulston, JE ;
Taylor, K ;
Whitehead, S ;
Barrell, BG .
NATURE, 1998, 393 (6685) :537-+
[9]  
Cronan JE, 1996, ESCHERICHIA COLI SAL, V1, P206
[10]   Pathway alignment: application to the comparative analysis of glycolytic enzymes [J].
Dandekar, T ;
Schuster, S ;
Snel, B ;
Huynen, M ;
Bork, P .
BIOCHEMICAL JOURNAL, 1999, 343 :115-124