Enzyme Catalysis, Inhibition, and Regulation Part 1

How much do enzymes typically increase reaction rates?

10^6 to 10^14

Do enzymes change the free energy difference between reactants and products or the reaction’s equilibrium constant?

no

How do enzymes allow reactions to occur?

under milder conditions

How do enzymes affect the activation barrier?

reduce it

Are almost all enzymes specific?

yes

True or false: CYP450 enzymes involved in drug metabolism have a very broad substrate specificity?

true

What is induced fit?

Enzymes change their 3D shape upon substrate binding to increase the likelihood of the reaction occurring

What are oxidoreductases?

carry out oxidation-reduction reactions

What is an example of an oxidoreductase?

alcohol dehydrogenase

What are transferases?

transfer functional groups

What is an example of a transferase?

kinase

What are hydrolases?

carry out hydrolysis reactions (breaks a larger molecule into smaller molecules by adding H2O)

What is an example of a hydrolase?

chymotrypsin (a serine protease)

What are lyases?

cleave or form bonds in processes that do not involve oxidation, reduction, or hydrolysis

one substrate forms 2 products

What is an example of a lyase?

aldolase

What are isomerases?

perform isomerization reactions

What is a ligase?

form bonds between two molecules by breaking a high energy bond

What is an example of a ligase?

pyruvate carboxylase

What is acid-base catalysis?

protein functional group donates and/or accepts a proton during a reaction

What is covalent catalysis?

reaction is accelerated through the formation of a covalent enzyme-substrate bond

What is transition state binding?

preferential binding of the transition state of the reaction lowers the activation energy of the reaction

What is catalysis by proximity?

enzyme places the substrate(s) in the proper orientation for the reaction to occur and restricts unfavorable orientations

What are 2 examples of catalysis employing cofactors?

coenzymes

metal ions

Can an enzyme use multiple strategies for catalysis?

yes

Which catalysis methods does chymotrypsin use to carry out hydrolysis reactions?

acid-base catalysis, covalent catalysis, transition-state binding

What are some examples of serine proteases besides chymotrypsin?

trypsin, elastase, thrombin

What is the catalytic triad found in chymotrypsin?

Asp, His, Ser

In which step of the serine protease reaction is an oxyanion intermediate formed?

step 1

The transition state in the previous flashcard with an oxyanion is stabilized by what?

hydrogen bonding with backbone amide hydrogens in the oxyanion hole (specialized region of enzyme) which lowers the activation energy of the reaction

What are some examples of coenzymes important to catalysis?

NADP+/NADPH

thiamine pyrophosphate (TPP)

coenzyme A

folate

What are the oxidation-reduction coenzymes?

NADP+/NADPH

What is an example of an activation-transfer coenzyme?

TPP

What is an example of an enzyme that uses TPP as a coenzyme?

pyruvate decarboxylase

How does TPP work as an activation-transfer coenzyme?

the pyrophosphate portion of TPP binds to the enzyme, while the thiazolium ring of TPP participates in the decarboxylation of a-keto acids

What are the roles of metal ions as cofactors?

orient substrates for a reaction

shield or stabilize negative charges

donate or accept electrons in oxidation-reduction reactions

Reversible inhibitors bind to the enzyme via _________ interactions.

non-covalent

Irreversible inhibitors bind to the enzyme via __________ interactions.

covalent