Redox Reactions III

Question 1

What reaction does cytochrome oxidase catalyse?

Answer 1

4 electron reduction of oxygen to water

Question 2

What defines reactivity of oxyferryl heme species?

Answer 2

The proximal ligands

Question 3

What is the function of cytochrome p450 enzymes?

Answer 3

Involved in:

• Drug metabolism
• breakdown xenobiotics

Question 4

What cofactors does p450 contain?

Answer 4

Heme B centre

Question 5

What is phase I metabolism?

Answer 5

Oxidation by p450 to make a polar, water soluble substance

Question 6

What happens in phase 2 metabolism?

Answer 6

Conjugation by adding an ionizable group

Question 7

What reaction do p450 enzymes generally catalyse?

Answer 7

the insertion of an oxygen into a C-H bond

Question 8

Why are p450 enzymes so called?

Answer 8

Named after the principal absorption band of ferrous-CO complex

Question 9

What is the equation for the general reaction of p450 enzymes?

Answer 9

R-H + O-O + 2e^- + 2H⁺ → R-OH + H₂O

Question 10

Where are p450 enymes present in high concentration?

Answer 10

The liver

Question 11

Why are p450 profiles important?

Answer 11

To understad pharmacokinetics and adverse drug reactions

Question 12

What bond is key to the oxidisng power of p450?

Answer 12

Cysteine thiolate-Fe bond

Question 13

Which might p450 use electrons from H₂O₂ rather than NADPH?

Answer 13

NADPH is an ‘expensive’ molecule

Question 14

Why is p450 compound 1 tightly regulated?

Answer 14

It is one of the most reactive intermediates found in nature

Question 15

What occurs in the mechanism of p450 when hydrogen peroxide is used as the electron donor?

Answer 15

The peroxide shunt pathway occurs and p450 is forced to bypass steps

Question 16

Why are p450s promiscous?

Answer 16

Certain p450s have a large active site, can generate very reactive species, and bring substrate close by

Question 17

What do some bacteria use p450 for?

Answer 17

To grow on toxic or halogenated organic molecules

Question 18

How can p450s be involved in cancer?

Answer 18

p450 enyme aromatase plays a large role in oestrogen related breast cancer

Question 19

What does aromatase do?

Answer 19

Aromatises androgens into oestrogens

Question 20

What does the aromatase inhibitor do?

Answer 20

Bind directly to the heme iron wither using an azole or triazole group

Question 21

Why is p450 useful in industry?

Answer 21

• Generate new drugs
• Important in antibiotic/drug biosynthesis

Question 22

How has p450 been used in industry?

Answer 22

Yeast strains have been engineered to produce plant p450 to perform last step of biosynthesis of a malaria drug (Artemisinin)

Question 23

What reaction does monoamine oxidase catalyse?

Answer 23

RCH₂-NH₂ + O₂ + H₂O →R-CHO + H₂O₂ + NH₃

Question 24

What is the general function of monoamine oxidases?

Answer 24

Degrading neurotransmitters

Question 25

What cofactor does monoamine oxidase use?

Answer 25

FAD

Question 26

Roughly how does monoamine oxidase work?

Answer 26

• Removes hydride from substrate
• Regenerates by reacting O₂ to produce H₂O₂
• Imine bond is hydrolysed, forming aldehyde product

Question 27

What are class I of p450 reductases?

Answer 27

• 3 component
• Assemble transiently

Question 28

What are class II of p450 enzymes?

Answer 28

• Microsomal
• 2 component

Question 29

What are class III p450 reductases?

Answer 29

• Bacterial
• 1 component