This presentation is about the drug metabolism or dexotification of chemicals and drugs. This will help for those who are in pharmaceutical industry or studying toxicology
2. WHAT IS XENOBIOTICS ?
Derived from Greek word
(Xenos- Foreign + Bios- life)
Xenobiotics is defined as a
chemical or molecule that is
foreign to the body and exerts a
variety of effects on the biological
system.
These effects may be beneficial,
in case of drugs, or deleterious,
in case of poisons.
3. NEED OF BIOTRANSFORMATION
Xenobiotics are mostly lipophilic in
nature due to which they are easily
penetrate the lipoprotein bilayer and
cannot easily eliminated from the
body. Without biotransformation
liphophilic xenobiotics would be
excreted from the body very slow, this
may produced lethal effect.
4. BIOTRANFORMATION
The biologically catalyzed conversion
of one form of xenobiotics into another
form may be simply termed as
Biotransformation.
In other words, the conversion of
lipophilic chemicals are biocatalytically
converted into their hydrophilic forms
that are easily excreted from the body
of organisms.
5. BIOTRANSFORMATION
SITES The organ/tissue where in the
biotransformation takes place is called
biotransformation site.
The biotransformation of toxicant are often
catalyzed by the enzyme which is mainly
occur in liver of vertebrate.
In the vertebrate these enzymes are also
occur in the skin, kidney, lungs, intestine,
placenta, gonads, embryonic layer,
adrenal gland but not in nervous system.
In insects such enzymes have been
reported in mid-gut, fat bodies and
malpighian tubules.
6. MECHANISM OF BIOTRANFORMATION
R.T. William 1959 studied the
mechanism of biotransformation
of xenobiotics and divided
biotransformation into two phages
a) Phase I reaction(non synthetic
reaction)
b) Phase II reaction (synthetic
reaction)
8. OXIDATION
Great variety of xenobiotics involves
oxidation process, the most important
enzymes catalyzing the involved
process of a Cytochrome P-450 and
NADPH+ reductase.
Oxidation of various toxicant is
catalyzed by:-
◦ Microsomal Oxidation,
◦ Non-Microsomal Oxidation
11. NON MICROSOMAL
OXIDATION
Apart form microsomal mixed function
oxidases , several other enzymes
(eg.Oxidoreductase) are located in
the mitochondrial fraction of tissue
homogenates.
- Amine Oxidaton:- In the presence of
enzyme Monoamineoxidase.
13. HYDROLYSIS
Hyrdolysis is the only phase 1
reaction, which does not utilized
energy, such as esters, amides or
substituted phosphates containing
ester bonds.
14. PHASE II REACTION
Conjugation reaction:-
Generally, the conjugation
reaction involves addition of polar
and readily available endogenous
molecules to the xenobiotics or
their Phase 1 products.
16. CONJUGATON REACTIONS
GLUCURONIDATION
Most important reaction in Phase II
-OH or –COOH group are congujated with
glucuronic acid by UDP- Glucuronosyl Tranferases
(UGTs) to form corresponding Glucuronides
Examples:- Aspirin, Paracetamol, Morphine etc.
SULPHATE CONJUGATION
Supfotransferases (SULTs) conjugate sulphate to
the hydroxyl and amine groups of aromatic and
aliphatic compounds.
Examples:- Chloramphenicol, Methyldopa, Adrenal
and Sex Steroid
17. CONJUGATON REACTIONS
GLUTATHIONE CONGUATION
Inactivate highly reactive quinone or epoxide
intermediates of some drugs and protects body
It is done by Glutathione S- transferase (GST)
enzyme by making mercapturic acids and excrete
via urine or bile.
Example:- Paracetamol
ACETYLATION
Compounds having amino or hydrazine residues
are conjugated with the help of N- acetyl
transferases (NATs)
18. CONJUGATON REACTIONS
Examples:- Sulfonamide, Isoniazid, PAS, Dapsone
etc.
Methylation
Amines and phenols can be methylated by
Methyl Transferases (MTs)
Examples:- Nicotinic acid, Methyldopa,
Captopril etc.
19. FACTORS AFFECTING
BIOTRANSFORMATION:-
Various factors related to the
chemical, the environment and the
physiological state of organisms affect
the rate and relative importance of
biotransformation.
These factors can be divided into
three categories:
a) Chemical factor
b) Environmental factors
c) Factors related to the organism
