Rice Flashcards
Why study enzymes?
- pose challenging and interesting questions
- excellent catalysts even though limited repertoire of functional groups
- operate in water at 37° and pH4-9 (also extremophiles)
- often use add chem species, eg. metals, coenzymes, to augment functions of 20AAs
- medium sized molecules –> are parts of protein removed from active site important?
- key to metabolism so hope to soon predict function from gene seq and understand control and reg of metabolism
- inhibitor design to modulate metabolism
- goal of designing new enzymes de novo
- industrial use of enzymes big business
Where are enzyme names usually derived from?
- substrate or reaction catalysed and ase
What are isoenzymes?
- same function and same basic name
- but diff AA seqs
How can isoenzymes sometimes be distinguished?
- diffs in optimal pH, kinetic properties or immunology
What is the nomenclature for enzymes?
- described by 4 no.s
- 1st broadly classifies mechanism
- then subdivided into sub-families
- then sub-sub-classes
- 4th no. specific to enzyme
What are the 6 broad classifications of enzyme?
- oxidoreductases = cat ox/red reactions
- transferases = transfer functional group
- hydrolases = cat hydrolysis of various bonds
- lyases = cleave various bonds, not using hydrolysis/ox/red
- isomerases = cat intramol isomerisation changes
- ligases = join 2 molecules by covalent bonds
What was the lock and key model?
- substrate exact fit for active site and forms ES comples
What was Haldene’s enzyme model?
- substrate in shape complementary to transition state, as stabilisation enhances rate
- most of enzyme has no active role and req for optimal orientation of active site
What was Pauling’s model?
- substrate complementary to active site
- strong bonds to transition state and weak to reactants/products
What was Koshland’s model?
- induced fit
- enzymes flexible and active site continually reshapes as result of interactions w/ substrate until completely bound, then catalysis occurs
What is the transition state?
- transient entity formed in conversion of reactants to products
- max energy point along reaction path
Can the transition state be isolated, why?
- no
- lifetime is 1 bond vibration
- may have partial or imaginary bonds and more ligands bound to atom than standard valency supports
What is activation energy?
- diff between energy of transition state and reactants
What does the energy profile diagram for a 1-step chemical reaction show?
- DIAG*
- larger the activation energy, the slower the reaction
- larger the net free energy charge, the more irreversible the reaction
- exo reaction has products of lower free energy than reactants
What does the energy profile diagram for a 2-step chemical reaction show?
- DIAG*
- intermediate formed in conversion of reactants to products
- transition state remains point of highest energy
- activation energy still diff between energy of transition state and reactants
- can only isolate intermediate if energy low enough
What does Pauling’s concept as an energy profile diagram show?
- DIAG*
- enzyme catalysis lower energy of transition state by more than lowering of reactants/products
What are the diff types of catalysis enzymes use?
- covalent –> nucleophilic and electrophilic
- acid
- base
- metal ion –> electrophilic, ligand activation, redox
- strain
- conformational organisational –> entropic control
What are some of the key functional groups in enzymes?
- Cys, Ser/Thr, Tyr, Asp/Glu, Lys, His, Asn
What is the role of co-enzymes in enzyme catalysis?
- augment role of key AAs
What are the properties of the C-O-H group in Ser/Thr?
- DIAG*
- no resonance structures for anion, so not acidic (pKa = 15)
What are the properties of the C-O-H group in Tyr?
- DIAG*
- 4 resonance structures of phenolate ion, so mod acidic (pKa = 10)
What are the properties of the C-O-H group in Asp/Glu?
- DIAG*
- 2 resonance structures for carboxylate anion, so quite acidic
What are the properties of the C-N-H group in Lys?
- DIAG*
- no resonance structures, so weak acid and strong base (pKa ≈10)
What are the properties of the C-N-H group in His?
- DIAG*
- imidazole cation stabilised by 2 equivalent resonance structures, so moderate acid and base (pKa ≈7)