Transition State Analogs in Enzymology

University:
Swansea University
Course:
PM-133 | Evolutionary and Molecular Genetics
Academic year:

2023
Views:

345

Pages:

3
Author:

Amal J.

Transilion state analogsbest/most potent inhibitorsEg:- Peolin racemase of Pyrole 2. CarboxylateDprolineLprolinemimic the transition state involvedin the reaction.Pyrole 2 carboxylate interact withactivesit. e of proline reacemaremuch better than D-proline.Reversible InhibitorsIUncompetativeMixedCompetativeNon-competative.1 CompetativeBinding site of substrate & inhibitor in same, they compete for the bindinE+PK1K2EtsESE+SESE+PE+IEIX+IVmax = K2 [ET]This inhibition can be overcome byno changeincreasing the sohstrate.Kmax - K2+K-1EIchaing in (K2)Km icleases by Laffinity. changeXKm2Km (apparent KM)Km = [s] = @half maximal velocity(1/2Vmax)inhibitornormal LBYmax do not canchange1Km increases by aVoEg: . Jbup rufen - inhibit prostaglordin synthase.Vmax(same)Statin - Drug for loweing cholestrol level,inhibit enzymes involvedin cholesterolbioxynthesis. HMG CoA synthase Reductive-Aminoptain & methotrexate1/km KmIboth inhibit dihydiofolate reductane[s] IDHFRMethotrexate - used as anticance drug, impairproperreplication.DHFTetraliydio folate(THf)ThymidylateCH3transainesynthaseGlycineCTMPMethyl TetraHydeofolate(MTHF)duMPEthanolMelbanolformaldehyde toxic,cause tissuedamage, especially jeyesAlcohol DehydrogenaseEthanolAcetaldebydcnotoxic.If a pay person in suffering from methanol poironing ,ethanol ingiven which competes for the active site of Alcohol dehydeogenanereduce chance of(2) Uncompetitive InhibitionSubstrate and inhibitor binding site are differentInhibitor bind to E.S complexto overcome this ,00 use of [s], [s] if VmaxE +SESE+P+IEg:- Glyphosatel RoundUp1EPSP synthaseVmaxYmaxESIKmkm2'alomatic aa synthesis1inhibitor(shiminate pathway).1no inhilYo Competitive + Uncompetitive94E+SESE+P1inhibitor+tVonoinhibitor.IIYvmaxIVmaxEIES.I.1/km -1/km1/65]xVmaxx km2'''(4)Non- competitive inhibitiony1inhibitorEg:- Lead -VmaxIVokmEnzymes withpochangenoishibitorcysteine in theiractive site.VmaxKm (same).1/553XCs]KmTypeVmaxC. UNM& KimKm-CIVmexVmax1-kmVmaxUIad'a kinMIYmax2