Enzymes I and II

Question 1

2 functions of enzymes

Answer 1

1. Proteins that control the kind of chemical reactions that can occur 2. Control the rate of reactions

Question 2

Enzyme structure and domains

Answer 2

Have primary, secondary, and tertiary structure. Different domains with different functions including prodomain, catalytic domain, substrate-binding domain, transmembrane domain

Question 3

Substrate

Answer 3

Molecule that the enzyme acts upon

Question 4

Substrate-binding site

Answer 4

Specifically recognizes a particular substate (or limited number of substrates). Reason why enzymes show high specificity.

Question 5

Catalytic site

Answer 5

Contains residues that catalyze the reaction by acting on the substrate (often helped by cofactor)

Question 6

Active site

Answer 6

Substrate-binding site + catalytic site

Question 7

3 ways to categorize enzyme inhibitors

Answer 7

1. Reversible vs. irreversible 2. Competitive vs. non-competitive 3. Selective vs. non-selective

Question 8

Exogenous inhibitors

Answer 8

Administered to the body

Question 9

Endogenous inhibitors

Answer 9

Present in the body, naturally occurring

Question 10

Zymogen

Answer 10

Also called a pro-enzyme. Inactive form of the enzyme which requires activation (often by another enzyme).

Question 11

6 types of enzymes

Answer 11

1. Oxioreductases 2. Transferases 3. Hydrolases 4. Isomerases 5. Lyases 6. Ligases

Question 12

Oxioreductases

Answer 12

Transfer hydrogen or oxygen from one substrate to another–redox reactions (e.g. oxidases)

Question 13

Transferases

Answer 13

Transfer functional groups from one substrate to another (e.g. kinases)

Question 14

Hydrolases

Answer 14

Catalyze hydrolysis of a substrate–add water across a bond (e.g. digestive enzymes)

Question 15

Isomerases

Answer 15

Change the molecular form (isomer) of a substrate

Question 16

Lyases

Answer 16

Remove or add a group to the substrate in a non-hydrolytical way–add/remove water, ammonia, carbon dioxide across double bond (e.g. carboxylases)

Question 17

Ligases

Answer 17

Join 2 molecules through formation of bonds between C and O, S, N (e.g. citric acid synthetase) using ATP

Question 18

4 ways to regulate enzyme activity

Answer 18

1. Substrate availability 2. Enzyme availability 3. Enzyme activation 4. Enzyme inhibitors

Question 19

Substrate availability

Answer 19

Amount of substrate determines rate of reaction. Location of the substrate and conformation of the substrate also important.

Question 20

Enzyme availability

Answer 20

Transcriptional and translational up or down regulation, de novo synthesis (small molecules to large ones)

Question 21

Amyloid precursor protein (APP)

Answer 21

Processed by secretases. Mutant type in Alzheimer’s 1000x better substrate for _-secretase than wild type. _-cleavage and _-cleavage lead to plaques but _-cleavage pathway does not. Blocking _-secretase could prevent plaques.

Question 22

5 pillars of inflammation

Answer 22

1. Heat 2. Redness 3. Swelling 4. Pain 5. Loss of function

Question 23

Prostaglandins

Answer 23

Key mediators of inflammation

Question 24

Cyclooxygenase

Answer 24

Cox: enzyme that turns arachidonic acid into prostaglandin H. Two types: Cox-1 and Cox-2

Question 25

Cox-1

Answer 25

Constitutively expressed.

Question 26

Cox-2

Answer 26

Induced by inflammation.

Question 27

Cox inhibitors

Answer 27

Potent anti-inflammatory drugs. General Cox inhibitors have GI side effects, but not Cox-2 inhibitors.

Question 28

Trypsinogen

Answer 28

Zymogen of trypsin secreted by pancreas. Activated in the bowl by enzyme called enterokinase.

Question 29

Enterokinase

Answer 29

Enzyme which activates trypsinogen in the bowl

Question 30

Trypsin

Answer 30

Derived from pancreas. When active attacks other zymogens and result in digestion of peptide bonds in food proteins

Question 31

Pancreatitis

Answer 31

Inflammation of the pancreas. Excess active trypsin over endogenous inhibitor which results in massive activation of these enzymes in the pancreas. Severe pain, vomiting, abdominal rigidity, fever, shock. High lethality.

Question 32

Proteases

Answer 32

Hydrolases which cleave peptide bonds in proteins. Involved in maturation of viral proteins, digestion, intracellular protein degredation, controlling biological processes (blood pressure, clotting cascade, immune response, apoptosis), remodeling ECM.

Question 33

4 major classes of proteases

Answer 33

Grouped by mechanism used to form nucleophile that attacks peptide bond 1. Serine proteases (e.g. trypsin) 2. Aspartyl proteases (e.g. HIV protease) 3. Metalloproteases (e.g. MMPs) 4. cysteine proteases (e.g. caspases)

Question 34

Metalloproteases

Answer 34

Use a metal (Zinc) to coordinate and activate attacking water molecule

Question 35

Endochondral ossification

Answer 35

Vessels grow into the bone, cavity forms, and ossification results in degraded cartilage (Arthritis)

Question 36

MMP

Answer 36

Matrix metalloproteases

Question 37

3 examples of remodeling using metalloproteases

Answer 37

1. ECM remodeling as part of normal growth/development 2. Pathological remodeling during diseases like arthritis 3. Cancer cells use proteases to invade tissues

Question 38

3 families of Zn-dependent metalloproteases

Answer 38

1. MMPs 2. ADAMTS 3. ADAM

Question 39

ADAM

Answer 39

A disintegrin and metalloproteinase

Question 40

ADAMTS

Answer 40

A disintegrin and metalloproteinase with thrombospondin motif

Question 41

EDS type VIIC

Answer 41

Dermatosparaxis: caused by mutation in ADAMTS-2 leading to disorganized collagen fibers which cause skin and connective tissue problems.

Question 42

_2-macroglobulin

Answer 42

Endogenous protease inhibitor produced in the liver with bait region containing cleavage sites for many enzymes. When bait region is cleaved conformation changes and traps enzyme which inactivates it.

Question 43

Safety considerations with developing enzyme inhibitors as drugs

Answer 43

1. Selectivity 2. Tissue distribution of targeted enzyme 3. Reversible vs irreversible inhibitors

Question 44

Irreversible inhibitors

Answer 44

Do not dissociate from enzyme so only way to restore activity is to synthesize more