Enzymes Flashcards
Enzymes
- large globular proteins
- catalyze chemical reactions in biological systems
- efficient
- specific (one to one)
- unchanged by the reaction
- lower activation energy required to reach transition state
Active site
- part of the enzyme, where the substrate binds
- specific AA side chains at the active site
what are the 2 models for specificity
lock and key
induced fit - substrate approaches and induces a change in active site so that it fits
Coenzymes
- many are derived from vitamins (all water soluble vitamins have some coenzyme role)
- Coenzymes are not specific to one enzyme, they can assist a number of different enzymes even though those enzyme catalyze different reactions
- so one coenzyme can play a role in many rxns!
Water Soluble Vitamins:
- *Nicotinic Acid
- *Riboflavin (B2)
- Thiamin (B1)
- Folic Acid/cobalamin (B12)
- Pyridoxine, pyridoxal, pyridoxamine (B6)
= NAD+/NADP+ - hydrogen and electron carriers in oxidation and reduction
=FAD/FMN - hydrogen and electron carriers in oxidation and reduction
=TTP - decarboxylation and acyl transfer
=TH4 - one carbon transfer, rearrangements, methyl-transfers
=CoASH - Transamination, decarboxylation, acyl transfer, carboxylation
Cofactors
-metal ion assisting the enzyme in the catalytic process
Oxidoreductases
oxidation reduction rxns
Transferases
transfer functional groups
-creatine kinase
Hydrolases
Hydrolysis rxns
Lyases
group elimination to form double bonds
Isomerases
Isomerization
Ligases
bond formation coupled with ATP hydrolysis
-DNA ligase
Define Turnover number
The rate of conversion of substrate to product (when the enzyme is fully saturated)
(amount of substrate that one enzyme can convert to product in a certain time)
What are the factors that affect enzyme activity?
PH - bell shapped (denaturation at PH extremes)
Temperature (faster until the protein denatures)
Enzyme concentration (more enzyme = faster rxn)
Substrate concentration (increases rxn rate until approaching vmax)
Substrate concentration
At low concentration rxn is first order
Near the maximum concentration the rxn is zero order (constant rate)
Km
substrate concentration at half the Vmax
- small Km reflects a HIGH affinity of enzyme for substrate (it doesn’t take a lot of substrate to reach half the max vel)
- large Km reflects a LOW affinity of enzyme for substrate
Types of enzyme inhibitors
reversible (competitive)
irreversible (non-competitive)
irreversible
-change Vmax!
Organophosphates
- block Ach-esterase
- by covalently binding a serine side chain at active site
- causes paralysis
- examples: Malathion (insecticide); Sarin (chemical weapon)
Aspirin (NSAID)
- inhibits cyclooxygenase (by covalently modifying it)
- without this enzyme can generate the clotting factors
- without clotting factors platelets don’t aggregate
- once platelets die effects of aspirin are lost
- good for acute treatment of gout (allopurinol for long term treatment)
reversible
competitive inhibitors don’t affect Vmax
however the Km of the enzyme is usually increased
examples:
sulfamides (first antibacterial agents - inhibit folic acid synthesis in bacteria
methotrexate (cancer therapy - inhibit folate activation)
Warfarin (used as an anti-coagulent)
Statins (inhibit rate limiting step of cholesterol synthesis)
Viagra
ACE inhibitors (cant convert to Ang II) - lower blood pressure - captopril / enalopril
Ibuprofen and Acetaminophen - transient effects like aspirin
example questions:
Alcohol can increase level s of uric acid (bc it contains high levels of purine
Other question a competitive inhibitor does what?
- allopurinol was the answer?
- increases the apparent Km
sulfonamides
bacterial infections
Dihydropteroate synthetase
methotrexate
various neoplasms (especially leukemia) Dihydrofolate reductase
*Allopurinol
gout
Xanthine oxidase
Ace inhibitors (captopril, enalopril)
high blood pressure
Angiotensin converting enzyme
