Redox Reactions III Flashcards
What reaction does cytochrome oxidase catalyse?
4 electron reduction of oxygen to water
What defines reactivity of oxyferryl heme species?
The proximal ligands
What is the function of cytochrome p450 enzymes?
Involved in:
- Drug metabolism
- breakdown xenobiotics
What cofactors does p450 contain?
Heme B centre
What is phase I metabolism?
Oxidation by p450 to make a polar, water soluble substance
What happens in phase 2 metabolism?
Conjugation by adding an ionizable group
What reaction do p450 enzymes generally catalyse?
the insertion of an oxygen into a C-H bond
Why are p450 enzymes so called?
Named after the principal absorption band of ferrous-CO complex
What is the equation for the general reaction of p450 enzymes?
R-H + O-O + 2e- + 2H+ → R-OH + H2O
Where are p450 enymes present in high concentration?
The liver
Why are p450 profiles important?
To understad pharmacokinetics and adverse drug reactions
What bond is key to the oxidisng power of p450?
Cysteine thiolate-Fe bond
Which might p450 use electrons from H2O2 rather than NADPH?
NADPH is an ‘expensive’ molecule
Why is p450 compound 1 tightly regulated?
It is one of the most reactive intermediates found in nature
What occurs in the mechanism of p450 when hydrogen peroxide is used as the electron donor?
The peroxide shunt pathway occurs and p450 is forced to bypass steps
Why are p450s promiscous?
Certain p450s have a large active site, can generate very reactive species, and bring substrate close by
What do some bacteria use p450 for?
To grow on toxic or halogenated organic molecules
How can p450s be involved in cancer?
p450 enyme aromatase plays a large role in oestrogen related breast cancer
What does aromatase do?
Aromatises androgens into oestrogens
What does the aromatase inhibitor do?
Bind directly to the heme iron wither using an azole or triazole group
Why is p450 useful in industry?
- Generate new drugs
- Important in antibiotic/drug biosynthesis
How has p450 been used in industry?
Yeast strains have been engineered to produce plant p450 to perform last step of biosynthesis of a malaria drug (Artemisinin)
What reaction does monoamine oxidase catalyse?
RCH2-NH2 + O2 + H2O →R-CHO + H2O2 + NH3
What is the general function of monoamine oxidases?
Degrading neurotransmitters
What cofactor does monoamine oxidase use?
FAD
Roughly how does monoamine oxidase work?
- Removes hydride from substrate
- Regenerates by reacting O2 to produce H2O2
- Imine bond is hydrolysed, forming aldehyde product
What are class I of p450 reductases?
- 3 component
- Assemble transiently
What are class II of p450 enzymes?
- Microsomal
- 2 component
What are class III p450 reductases?
- Bacterial
- 1 component
