Enzymes

Question 1

Principal Serum Enzymes

Answer 1

ALT (hepatitis), Amylase (pancratitis), Creatine kinase (muscle disorders and heart attack), lactate dehydrogenase isozyme 5 (liver disease), lipase (pancreatitis), acid phosphate (prostate cancer), alkaline phosphatase or isozymes (bone disorders or liver disease)

Question 2

Non plasma specific enzymes can appear in serum because

Answer 2

of damage to tissue of origin or because of “spillover” due to overproduction in tissue of origin (or a tumor in that tissue)

Question 3

mechanisms of enzyme regulation

Answer 3

reversible covalent modification, irreversible covalent modification, protein-protein interactions

Question 4

reversible covalent modification

Answer 4

example: phosphorylation, addition of phosphate

Question 5

irreversible covalent modification

Answer 5

example: zymogen - inactive precursor form of a protease that is activated by a specific proteolytic cleavage by another protease

enzymes are synthesized in an inactived form and activated irreversibly at a later time when they are needed

Question 6

protein-protein interactions

Answer 6

although zymogen activation is irreversible, activated proteases can be turned off by interaction with inhibitor proteins

ex: pancreatic tryprin inhibitor, anti-thrombin, a1-antitrypsin

Question 7

you can use enzymes as diagnostic tools by

Answer 7

measuring enzyme levels, measuring substrate/metabolite levels, isozyme distribution

Question 8

delta G

Answer 8

can predict whether a reaction can occur spontaneously (delta G < 0) but does not predict the rate of a reaction.

Question 9

chemical strategies in enzymatic catalysis

Answer 9

preferential binding of the transition state, proximity and orientation effects, acid-base catalysis, covalent catalysis, metal-ion catalysis, electrostatic catalysis

Question 10

preferential binding of the transition state

Answer 10

enzyme binds transition state structure with greater affinity than the substrate or products

enzyme fits transition state better than substrate and can form additional bonds to the transition state.

Question 11

acid base catalysis

Answer 11

transfer of proton with weak acid/base on enzyme (ex: histidine, aspartate, glutamate)

Question 12

covalent catalysis

Answer 12

transient formation of covalent bond between enzyme and substrate (new intermediate)

Question 13

metal ion catalysis

Answer 13

metal ions participate in catalysis

Question 14

electrostatic catalysis

Answer 14

charge distribution in active site helps stabilize the transition state

Question 15

serine proteases

Answer 15

brings together catalytic triad (aspartate, histidine, serine), 2 transition states, 1 intermediate, preferential stabilization of the transition state, breaks down reaction into two lower energy steps

Question 16

what determines substrate specificity in serine proteases

Answer 16

structural features near the active site dictate specificity

Question 17

suicide inhibitors

Answer 17

irreversible inhibitor, resembles substrate and binds to enzyme going through initial stage of catalysis to become an irreversible inhibitor.

ex: penicillin

Question 18

acetylcholinesterase

Answer 18

enzyme with both irreversible and reversible inhibitors

Question 19

catalytic triad

Answer 19

part of serine protease, consists of aspartate, histidine, serine

Question 20

aspartyl proteases

Answer 20

2 hydrogen bonded aspartates at the active site, acid-base catalysis with some preferential binding of the transition state, 1 transition state, no intermediates