detoxification of xenobiotics ppt biochemistry vkunder637@gmail.com

DETOXIFICATION OF XENOBIOTICS

Dr Vijay MarakalaBiochemistry

SIMS&RC

DETOXIFICATION OF XENOBIOTICS

• Detoxification pathways and waste disposal pathways are metabolic pathways devoted to removing toxins that can be present in our diets or in the air we breathe, introduced into our bodies as drugs, or generated internally from the metabolism of dietary components.

DETOXIFICATION OF XENOBIOTICSXe

nobio

tics • Food additives, poisons, toxins,

certain drugs, chemicals, environmental pollutants, pesticides and other foreign substances.

DETOXIFICATION OF XENOBIOTICS

Phases of Detoxification Processes

Phase I Phase II

DETOXIFICATION OF XENOBIOTICS

DETOXIFICATION OF XENOBIOTICS

DETOXIFICATION OF XENOBIOTICSOxidation Alcohol

Aldehydes

Amines

Aromatic hydrocarbons

Sulfur compounds

Drugs

Ethanol → Acetic acid

Methanol → Formic acid

Benzaldehyde → Benzoic acid

Aliphatic amine → Aliphatic acid + Urea

DETOXIFICATION OF XENOBIOTICSOxidation

Most of the oxidation reactions are catalysed by monooxygenase or cytochrom P450

Many reactions of cytochrome P450 involve

the addition of a hydroxyl group to xenobiotics

Hydroxylation

DETOXIFICATION OF XENOBIOTICS

DETOXIFICATION OF XENOBIOTICS

HydroxylationThe

responsible enzymes are

called monooxygen

asesor

cytochrome P450

DETOXIFICATION OF XENOBIOTICS

Cytochrome P450

DETOXIFICATION OF XENOBIOTICS

NADPH +H+

NADP+

NADPH –Cyt P450 reductase

NADPH –Cyt P450 reductase

Cyt P450

Cyt P450

XH

X-OH

oxidised

oxidisedreduced

reduced

O2

H2O

DETOXIFICATION OF XENOBIOTICS

Cytochrome P450

Multiple forms

Hemoproteins

Microsomes of liver

NADPH dependant

Phosphatidyl choline

Inducible enzyme

DETOXIFICATION OF XENOBIOTICS

Hydroxylation

DETOXIFICATION OF XENOBIOTICSReduction

It is less common and less important than oxidation.

DETOXIFICATION OF XENOBIOTICSHydrolysis Many drugs are detoxified by hydrolysis.

DETOXIFICATION OF XENOBIOTICS

Conjugation Glucuronic acid

Glutathione

Sulfate

Glycine

Cysteine

Acetate Glutamin

e

Conjugation means the chemical combination of one

compound with another compound.

DETOXIFICATION OF XENOBIOTICSConjugation with Glucuronic

acid

DETOXIFICATION OF XENOBIOTICS

Conjugation with Glucuronic acid

Benzoic acid + UDP-Glucuronic acid → Benzoyl glucuronide + UDP

Paracetamol + UDP-Glucuronic acid → Conjugated product + UDP

Diclofenac sodium + UDP-Glucuronic acid → Conjugated product + UDP

DETOXIFICATION OF XENOBIOTICS

Conjugation with Glycine

DETOXIFICATION OF XENOBIOTICS

Conjugation with Glutathione

DETOXIFICATION OF XENOBIOTICS

X-R + GSH

X-S-G

S-X-Cysteinylglycine

S-X-Cysteine

Mercapturic acid

RH

Glutamine

Glycine

Acetyl-CoA

CoA-SH

Glutathione S-transferase

γGlutamyl hydrolase

Cysteinylglycinase

N-Acetyl transferase

Conjugation reaction by glutathione

DETOXIFICATION OF XENOBIOTICS

Conjugation with Glutatmine

Phenylacetate

Phenylacetyl glutamine

Glutamine

DETOXIFICATION OF XENOBIOTICS

Conjugation with sulfate

DETOXIFICATION OF XENOBIOTICS