Enzymatic Reaction Steps E + S ES ES* EP E + P

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1 Enzymatic Raction Stps stp I stp II stp III stp IV E + S ES ES* EP E + P stp I stp II stp III stp IV binding of substrat (usually fast) formation of transition stat convrsion of transition stat to product rlas of product substrat transition stat product stp I stp II stp III stp IV E + S ES ES* EP E + P

2 Modls of Substrat Binding lock and ky modl s s nzym substrat nzym substrat / complx nzym binding sit is - rigid - complmntary to substrat inducd fit modl s s nzym substrat nzym / substrat complx nzym binding sit is - flxibl - conforms to substrat upon binding

3 Transition Stat Mchanism Strss on bond strss on bond s s + s s s* p p p p + p p Orint substrat s s substrats positiond corrctly + s s s* p + p p

4 Allostric Rgulation Positiv Allostrism ffctor binding activats nzym Ngativ allostrism ffctor binding inactivats nzym

5 Fdback Rgulation Low concntration of product in cll nzym is activ product binding sit Substrat Product High concntration of product in cll nzym is inactiv Substrat X Product ffctor binds on nzym conformational chang inducd

6 Phosphofructokinas Rgulation Phosphofructokinas (PFK) - controls glycolysis - snss if nough ATP in cll Effctor causs conformation chang in nzym. Enough ATP in Cll ATP P ATP binds to ffctor sit - turns PFK off - no glycolysis - no mor ATP mad Low ATP in Cll AMP ATP P AMP P P ADP AMP binds to ffctor sit - turns PFK on - glycolysis procds - ATP mad

7 Nuronal Transmission Actylcholin (Ach) is a nurotransmittr Must b dstroyd to stop impuls transmission Enzym Actylcholinstras hydrolyzs Ach stops signal O C O CH 2 CH 2 N + actylcholin O C actat + O - OH CH 2 CH 2 N + cholin Ach nuron impuls muscl contracts muscl rlaxs Ach rlasd from trminal nd of nuron Ach binds to rcptors on muscl cll hydrolyzs Ach... trminating nrv impuls

8 Organophosphat Nrv Gass stops nrv impuls by hydrolyzing Ach actat OH Ach Srin rsidu in activ sit cholin OH HC O P O Sarin Nrv impuls continus Muscls spasms Dath by laryngl spasm Psticids and inscticids work by sam mthod diffr by siz of sid chains small (toxic) larg (not so toxic) F O P O CH O Covalnt bond irrvrsibl inactivats nzym

9 Human Immunodficincy Virus (HIV) Normal Cll Virus binds to rcptor and ntrs cll Virus maks copis of its RNA and maks viral protins RT copis RNA to DNA thn DNA is insrtd into host cll's DNA Nw progny viruss ar assmbld Progny viruss ar rlasd into cytoplasm

10 HIV Mchanism RNA gag pol nv polyprotin innr coat protins intgras RT protas outr coat protins Protas xciss itslf and thn clavs th othr protins from polyprotin thrby producing activ virus parts. Each virus is thn packd with: 1) Rvrs Transcriptas 2) Intgras Why not packd with protas?

11 Major Histocompatibility Complx (MHC) pptid binding sit sugar molcul N N S S Extra-Cllular Rgion S S C Transmmbran Rgion Intrcllular rgion C Cll MHC All nuclatd clls hav class I MHC on thir surfac

12 Rols of MHC Whn cll infctd by virus, viral protins ar producd insid virus viral protin Infctd cll making viral protins MHC associats with viral protins insid cll Killr T-cll (K-T) K-T approachs infctd cll MHC "prsnts" viral protin on cll surfac Rcognizs "slf" MHC Killr T-cll (K-T) rcognizs viral protin

13 MHC Rols (cont.) Rcognizs "slf" MHC Killr T-cll (K-T) rcognizs viral protin Killr T-cll (K-T) K-T thn snds out chmical "bombs" that lys virus infctd cll! So MHC: (1) prsnts viral antigns to K-T clls (2) provids slf rcognition (3) Rason that transplants ar rjctd. (4) Tissu Typing involvs similarity btwn donor and rcipint MHC. Cll dstroyd

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