title: 'Domino' systems biology and the 'A' of ATP.
abstract: We develop a strategic 'domino' approach that starts with one key feature of cell function and the main process providing for it, and then adds additional processes and components only as necessary to explain provoked experimental observations. The approach is here applied to the energy metabolism of yeast in a glucose limited chemostat, subjected to a sudden increase in glucose. The puzzles addressed include (i) the lack of increase in adenosine triphosphate (ATP) upon glucose addition, (ii) the lack of increase in adenosine diphosphate (ADP) when ATP is hydrolyzed, and (iii) the rapid disappearance of the 'A' (adenine) moiety of ATP. Neither the incorporation of nucleotides into new biomass, nor steady de novo synthesis of adenosine monophosphate (AMP) explains. Cycling of the 'A' moiety accelerates when the cell's energy state is endangered, another essential domino among the seven required for understanding of the experimental observations. This new domino analysis shows how strategic experimental design and observations in tandem with theory and modeling may identify and resolve important paradoxes. It also highlights the hitherto unexpected role of the 'A' component of ATP.
authors.affiliation: Manchester Centre for Integrative Systems Biology, Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK.
authors.forename: Malkhey
authors.initials: M
authors.lastname: Verma
authors.forename: Maksim
authors.initials: M
authors.lastname: Zakhartsev
authors.forename: Matthias
authors.initials: M
authors.lastname: Reuss
authors.forename: Hans V
authors.initials: HV
authors.lastname: Westerhoff
mesh_terms: D000225:Adenine / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D004734:Energy Metabolism; D005635:Fructosediphosphates / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006868:Hydrolysis; D008954:Models, Biological; D019289:Pyruvic Acid / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D049490:Systems Biology; D013997:Time Factors
chemical_list: D005635:Fructosediphosphates; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D005947:Glucose; D000225:Adenine; C029063:fructose-1,6-diphosphate