Kinetic Evidence fora'Mnemonical' Mechanism forRatLiver Glucokinase

on results suggest thatglucose 6-phosphate isreleased first andthat itispossibly displaced byMgATP2-inaconcerted reaction. Ratliver glucokinase (ATP-D-glucose 6-phosphotransferase, EC 2.7.1.2) displays a co-operative dependence oftherateofreaction on theglucose concentration, witha degree ofco-operativity that increases withtheMgATP2-concentration (Storer & Cornish-Bowden, 1976b). However, noco-operativity canbedetected forthedependence oftherate on the MgATP2-concentration. Thisisdifficult toreconcile with asimple modelinwhichthesteady-state rateis assumed to mimicthebinding ofsubstrates at equilibrium (Monodetal., 1965; Kirtley & Koshland, 1967), because suchmodels usually require that a ligand thatalters thehomotropic interactions of another ligand should itself display homotropic interactions. Thisdoesnotrule outtheagencyofaquasiequilibrium modelmore complex thanthose considered byprevious authors, butitdoessuggest that steady-state models, suchas thoseproposed by Ferdinand (1966) andRabin(1967), oughttobe considered forglucokinase. Glucokinase appearstobemonomeric underall conditions, with amol.wt. ofabout 48000(Holroyde etal., 1976), approximately one-half themolecular weights ofthemammalian hexokinases (Colowick, 1973), which arealso monomeric andaresimilar in aminoacidcomposition bothtooneanother andto glucokinase; a new methodofanalysis (CornishBowden, 1977a) ofthedataforglucokinase andfor hexokinase typeII (Holroyde & Trayer, 1976) indicates about85%identity between theprimary sequencesofthetwoenzymes.Theseobservations notonlyexclude models based on reversible associationofglucokinase (Frieden, 1967;Nichol etal., 1967), buttheyalsoraise difficulties forallquasiequilibrium explanations ofglucokinase co-operativity. Itwouldbenecessarytopostulate the presence ofatleast twointeracting glucose-binding sites onthe