Class Note for BIOC 462A at UA 2
Class Note for BIOC 462A at UA 2
Popular in Course
Popular in Department
This 1 page Class Notes was uploaded by an elite notetaker on Friday February 6, 2015. The Class Notes belongs to a course at University of Arizona taught by a professor in Fall. Since its upload, it has received 15 views.
Reviews for Class Note for BIOC 462A at UA 2
Report this Material
What is Karma?
Karma is the currency of StudySoup.
You can buy or earn more Karma at anytime and redeem it for class notes, study guides, flashcards, and more!
Date Created: 02/06/15
Chemical Mechanism of Triose Phosphate Isomerase Triose phosphate isomerase represents the prototypical quotTIM barrelquot structure an interior parallel 3barrel surrounded by ochelical interconnections between 3 strands on3 barrel The enzyme is a homodimer each subunit having an active site near the carboxyl end of the barrel As the enzyme name tells you TIM sometimes called quotTPIquot also isomerizes triose phosphates specifically it interconverts glyceraldehyde 3phosphate an aldose and dihydroxyacetone phosphate the corresponding ketose in glycolysis and gluconeogenesis The isomerization can proceed in the absence of any catalyst through an unstable enediol intermediate but the uncatalyzed reaction is so slow that the aldose and the ketose are both stable compounds in the absence of a catalyst A catalyst must increase the concentration of the enediol by a lowering the free energy of the enediol intermediate stabilizing it and thus presumably also the transition state and b promoting the proton exchange required for enediol formation and thus increasing the rate AGO39 75 kJmol for the reaction shown below so the equilibrium favors DHAP The value for keenKM in the glyceraldehyde 3P 9 DHAP direction is 4 X 108 M3910sec391 However the reaction is reversible and the active site accommodates either sugar as a substrate the enzyme39s chemical mechanism is reversible In vivo the reaction is not at equilibrium when glyceraldehyde 3phosphate is being removed in glycolysis glucose catabolism DHAP is converted to glyceraldehyde 3phosphate When DHAP is needed for gluconeogenesis glucose synthesis glyceraldehyde 3phosphate is converted to DHAP H H 0 H OH x I s x 393 lcl H c OH A H C OH C OH I quotT T 3 0 CH20P03 H20P 3 OHZOP 03 Glyceraldehyde S plnsp hate vii enediol Dihydmxyawtonaphospahte The triose phosphate isomerase mechanism illustrates Transition state stabilization Acid base catalysis Electrostatic catalysis The triose phosphate isomerase mechanism provides an example of concerted acidbase catalysis The active site includes a Glu residue Glums thought to be the base 3 in the mechanism below as well as a His residue His95 thought to be the HA in the mechanism below and a Lys residue Lys12 The enzyme provides a quotcagequot in which the substrate is held by means of a quotlidquot loop of the enzyme that closes down upon the substrate to trap and protect the enediol intermediate from reacting with water The catalytic groups are perfectly positioned to carry out acidbase catalysis and also to stabilize the enediol Mutation of the Glu to anAsp moving the catalytic COO group just 01 nm further from the substrate results in a lOOOfold reduction in catalytic rate The chemical mechanism is thought to proceed as follows H O H H t c quot cOquot H E On 7 3d C as t HampEBH n A r 39A H lc OH Co H39 CO H t t LHEOPOH CHZOP03L CHZOPO3 0 GBP binds to the 9 Enedtol mtermedtates B39 Gtu tGS 0A proton tS returned acttve sne picks up the C72 proton HA donates from BH to C4 A a proton to make OH on CA1 accepts a proton from the OH on 02 gtvrng DHAP The GluCOO39 B39 extracts the proton from C2 so acm as a general base simultaneously the His imidazole group AH donates a proton to the C1 carbonyl 0 general acid enhancing the rate of formation of the enediol Then the GluCOOH donates its proton to C1 general acid and the His accepts a proton from the C2 OH group
Are you sure you want to buy this material for
You're already Subscribed!
Looks like you've already subscribed to StudySoup, you won't need to purchase another subscription to get this material. To access this material simply click 'View Full Document'