title: Design of glycolysis.
abstract: The design of the glycolytic pathway resulting from the continuous refinement of evolution is discussed with regard to three aspects. 1. Functional and structural properties of individual enzymes. The catalytic constants of the glycolytic enzymes are remarkably optimized; the turnover numbers are within one order of magnitude. The same is true for the molarities of catalytic centres in the cytosol, as is noted for yeast. Functional properties of the enzymes are reflected in their tertiary and quaternary structures. 2. Regulatory mechanisms of single enzymes. A classification of the various types of enzymic control mechanisms operating in the glycolytic pathway is given. In addition to the usual Michaelis-Menten saturation kinetics and the various types of inhibition there is control by positive and negative effectors based on oligomeric structures (fast acting, fine control) as well as regulation by chemical interconversion structures (fast acting, fine control) as well as regulation by chemical based on enzymes cascades (slow acting, very effective). 3. Functional and regulatory mechanisms of the whole glycolytic reaction pathway. A prominent feature is the high enzyme:substrate ratio, which guarantees fast response times. However, a quantitative treatment of the overall kinetics is limited by an incomplete knowledge of the enzymes' dynamic and chemical compartmentation as well as some of their control properties. From an analysis of the oscillatory state, certain control points in the glycolytic chain can be located that coincide with major branching points to other metabolic pathways. These points are controlled by fast-acting cooperative enzymes that operate in a flip-flop mechanism together with the respective antagonistic enzymes, preventing futile cycles. The gating enzymes leading to the glycogen store and the citric acid cycle are of the slow-acting but very effective interconvertible type. The combination of all the complex and intricate features of design yields a glycolytic network that enables the cell to respond to its various metabolic needs quickly, effectively and economically.
mesh_terms: D000818:Animals; D001419:Bacteria / Q000201:enzymology; D004798:Enzymes / Q000378:metabolism*; D005658:Fungi / Q000201:enzymology; D006003:Glycogen / Q000096:biosynthesis; D006019:Glycolysis; D007535:Isomerases / Q000378:metabolism; D007700:Kinetics; D008190:Lyases / Q000378:metabolism; D046911:Macromolecular Substances; D008954:Models, Biological; D010088:Oxidoreductases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011487:Protein Conformation; D014166:Transferases / Q000378:metabolism
chemical_list: D004798:Enzymes; D046911:Macromolecular Substances; D006003:Glycogen; D010088:Oxidoreductases; D014166:Transferases; D010744:Phosphoric Monoester Hydrolases; D008190:Lyases; D007535:Isomerases