if you have a headache or backache can

you take your chalk to block the pain

you'll notice that the effects of the

drug wears off in a few hours have you

ever wondered how does this happen in

your body has this question kept you

awake at night

I'm sure it has but don't you worry

because I have the answer for you today

this happens because of cytochrome p450

enzymes cytochrome p450 is a super

family of enzymes involved in drug

metabolism and bio activation the most

important role of the super family of

enzymes is the breakdown of xenobiotics

and humans xenobiotics are essentially

substances that you introduce into your

body that are foreign to your body such

as medicine or drugs that you intake the

location of this breakdown is

predominantly the liver so essentially

the biggest role of cytochrome p450

enzyme is to turn drugs into soluble

molecules so that it can be excreted out

properly the active site of cytochrome

p450 contains a heme iron Center

specifically Hindi Hindi samosa bud 19

it is also present in hemoglobin and

myoglobin heme consists of this complex

organic ring structure called proto

porphyrin to which a single iron atom is

bound the iron atom is bound to the four

nitrogen of the porphyrin ring system

forming a plane in cytochrome p450 the

heme is also key leading to another

molecule the cysteine residue so the

iron is ultimately held in the center

with the nitrogen of the ring as well as

sessile of the cysteine residue holding

it from the bottom within the cytochrome

p450

there are many different kinds of p450

enzymes but they all attain similar

structure here we're looking at the

crystal structure of p450 bm3

this has 13 alpha helixes and 5 beta

sheets the alpha helixes are presented

as purple coils 310 helix and paahe

lucy's as green coils beta strands as

red arrows and beta loops are

represented as yellow tubes the amino

and carboxyl terminal has also been

labeled the cysteine residue loops

present just prior to the L helix this

rigid architecture is required to both

protect the cysteine legen and hold it

in place in order to accept protons the

other highly conserved region involved

in Oh to activation is the portion of

helix near the heme iron when the

interaction between the oxygen and iron

is taking place oxygen enters on the

opposite side of soil and always enters

at an angle it never enters in

perpendicular manner so let's discuss

how exactly to the cytochrome p450

enzymes work in the beginning the iron

in the cytochrome p450 will be in this

ferric state 3 plus state the our region

the mechanism represents the drug our

being the variable region as the cycle

begins the first step involves the

enzyme coordinating or combining with

the drug and giving the enzyme

cytochrome p450 with the substrate our h

complex in the second step the enzyme

substrate complex will get reduced by

NADPH NADPH will get oxidized to nad

plus while the electron gets transferred

to the enzyme substrate complex so now

the oxidation state of the enzyme is Fe

2 plus so the second step involves

reduction of the enzyme complex and

oxidation of the NADPH in the third step

oxygen molecule comes in an electron

from iron it gets transferred over to

the oxygen and it then produces this

complex so the iron in the cytochrome

p450 has been oxidized it has

austan electron whereas oxygen has been

reduced it has gained an electron step

four is similar to step two

NADPH gets oxidized to nad plus transfer

an electron to the complex however note

that electron is not accepted by the

iron atom instead it is accepted by the

oxygen atom in the first step two

protons are added the protons interact

with the enzyme-substrate oxygen complex

two electrons as well as one of the

oxygens from the complex gets

transferred to the protons which

therefore produces a water molecule

the reason this occurs is to the fact

that two oxygens in the enzyme complex

are covalently bonded in order to break

the bond water molecule needs to be

formed steps one to five are essentially

preparing the substrate for the next

step where the drug actually gets

modified in this step the remaining

oxygen will get transferred over to the

substrate

it is bellissimo dynamically and

kinetically favorable for this to occur

once this transfer occurs the enzyme is

able to release the metabolite the

product ROH once I RH gets released

we're left with the original cytochrome

p450 enzyme in its default ferric state

so now the enzyme is ready to begin the

cycle all over again

as previously mentioned cytochrome p450

enzymes play a crucial role in drug

metabolism metabolism is often divided

into two parts phase 1 metabolism and

phase 2 metabolism phase 1 can involve

reduction or hydrolysis but the most

common biochemical process that occurs

is oxidation oxidation is catalyzed by

cytochrome p450 enzyme as we just found

a mechanism cycle of cytochrome p450

enzymes phase 1 reactions convert a pair

and drug to a more polar water-soluble

metabolite by unmasking or inserting a

polar functional group however after

Faison reactions the resulting drug

metabolite is often still chemically

active so it must go through phase 2

metabolism before it can be excreted

phase two involves conjugation reactions

which means attachment of an ionized

group to the drug these groups include

glutathione methyl or acetyl groups the

attachment of an ionized group increases

the virus or the ability of the

metabolite as well as decreases the

pharmacological activity so after going

through phase jamot AB ilysm the drug

becomes inactive these drugs are then

green only excreted let's take the

example of aspirin aspirin undergoes

phase 1 metabolism with cytochrome p450

enzyme and gets converted to salicylic

acid in phase 2 it is conjugated with

either glycine or glucuronic acid

forming a range of ionized metabolites

that can then be excreted in the urine

I hope everyone learned a little

something about cytochrome p450 enzymes

today now all of you can go to bed and

peace as your ultimate question about

drug metabolism has been answered