Metaboism W7 Flashcards
Drug metabolism is divided into two phases
Phase one produces or uncovered a chemically reactive functional group and prepare the drug for phase 2
Phase 2 conjugate the functional group and set it up for excretion
P450 enzymes
Blow torch family of enzymes = oxidise anything
Very nonpolar
Need to know how to draw a representation of P450 enzyme
A mushroom like shape/kind of looks like a dummy
Has a large lipophilic cavity where the drugs can enter in different orientations
A thick line on the outside in a darker colour will show the active site
On the bottom drawer, a straight line all the way across
What is the haem group?
Highly redox active
Why are they called CYP450 enzymes?
Because when reduced and complex with CO, they have a characteristic absorbance at 450nm
Key CYP facts
Heme containing enzyme
Membrane bound protein
Must be associated in a complex with a P450 reductase
Two most common CYP450 phase one conversion
Hydroxylation and dealkylation
What does hydroxylation do?
The hydrogen on the R atom which is attached to the iron of the reactive species is pulled off
It is then added on to the oxygen which is attached to the iron on the radical species
The hydroxy group is then removed from the iron
This leaves us with a reduced iron of FE3+
What does dealkykation reaction do?
This occurs after hydroxylation of an heteroatom (O, N,S or P)
If the attached OH group is next to the heteroatom then there is de-alkylation which leads to the bond between the OH group and the heteroatom been broken
If the OH group is further from the header atom, then it remains hydroxylised
Is the hemiaminal stable or unstable
Unstable
What is an hemiaminal
contains both a hydroxyl group (-OH) and an amino group (-NR₂ or -NH₂) attached to the same carbon atom.
For the rest of this look over the metabolism lecture
