Karteikarten
Lecture 10 - Mechanisms of enzyme mediated catalysis
Karten in diesem Stapel (15)
- 1Concepts to understandEnzymes catalyze reactions by:
-Bringing reacting groups to close proximity
-3D positioning of the groups by forming bonds, hydrophobic effect, water exclusion, role of polar residues and pH.
-Formation of transient bonds that reduce the activation energy
-Major types of reactions occurring in the active site
-Cofactors: essential ions and coenzymes
-Vitamins - 2Proximity effect = effecctive ___ increaseconcentration
- 3In 1894, Emil Fischer proposed an explanation of enzyme catalysis. It is often called 'lock and key' model The model explained catalysis due to proximity and enzyme specificity. However, it is failed to explain: enzyme ___ (tight fit should make ES quite stable); and why small changes in substrate molecules strongly reduce enzyme activity. In addition, the "lock and key" model does not explain ___ inhibition.kinetics
allosteric - 4In 1958, Danial Koshland proposed a modification of the lock and key model, which is referred to as an 'induced fit model'. The model takes into account that enzymes have flexible and ___ structures. More importantly, in this model, it is not the ES complex but the transition state ES that is ___.dynamic
stabilized - 5Catalysis is achieved due to: (i) energy increase ES vs. E+S (weak non-covalent bonds) (ii) energy decrease of ES vs. S (in ___ states) (iii) alternative reaction paths by forming transient bonds (iv) water displacement and ___ effecttransition
hydrophobic - 6Goldilocks balance in the formation of the transition state: Reactions with enzymes are reversible and intermediate complexes are not too stable to form _____ pits.thermodynamic
- 7Enzyme ___ the transition state Transition state analogs are better matched vs. substrates Transition state analogs act as more ____ competitive inhibitorsstabilizes
efficient - 8Enzyme catalyzed reaction proceeds through several transient chemical transformations that often include formation and breakage of ____ covalent bonds between E-S, S-P, and E-P. Nucleophilic attack (Nucleophilic substitution) is a common reaction type Other types of cleavage reactions include: -Oxidation-reduction (redox) rxns -->___ (electron gain) of oxygen is often source of energytransient
Reduction
- 9Protonation of -OH group is often used in biochemistry to weaken R-OH bond snd break it
- 10Enzyme E can catalyze reaction by forming and breaking covalent bonds. Enzyme active residue may be either ____ (more often) or electrophile. Transferases use coupled reactions (see figure)nucleophile
- 11What we have learned so far about enzyme catalysis: • Enzyme is a protein (often globular) that have a catalytic site(s) -This site is ___ with the inclusion of polar residues -These residues (often His) form ___ bonds with the substrate -Reacting groups have to be oriented in space and brought ___ • Formation of transient bonds between enzyme and substrate (ES) -Lowering of activation energy What we are about to learn: • Enzymes may NOT only be made out of proteins -Bio-catalysis often requires the help of non-protein molecules -These both organic and inorganic molecules & ions are ____hydrophobic
transient
close
cofactors - 12Example: Heme is a part of hemoglobin, but can also be a part of a protein ____. Cytochrome (co-enzyme) is a part of Cytochrome c Reductase. Cytochrome c Reductase is a part of the electron transfer chaincytochrome
- 13Magnesium ion (Mg2+) are ___ for DNA polymerases They position and stabilize deoxynucleotide triphosphates (dNTPs) Negative charges of phosphate groups are compensated by ____ Mg2+ ionscofactors
positive - 14Cofactors • Coenzymes are __-protein (for the most part) organic molecules -They often ___ a group of atoms or electron(s) to substrate -Nonfunctional enzyme that requires cofactor(s) to work: ___ • Complete and activated enzyme is ____ -Many coenzymes are __ synthesized. VITAMINS are precursors. -Co-enzymes can be continuously ___ without being consumed.non-
transfer
Apoenzyme
Holoenzyme
not
recycled - 15A, D, E, and K are the ___ vitamins; contain long hydrophobic chains. These fat-soluble vitamins are stored in fat tissues and the liver. Vitamin A deficiency is the leading cause of preventable childhood ___ in developing countries. Vitamin A is the precursor for a light-sensitive pigment in rhodopsin.lipid
blindness