Detoxification by Liver Phase 1 By Three steps Oxidation Reduction Hydrolysis

1. Detoxification : Phase 1
Parveen
92A

2. Def : It is meant all the biochemical processes whereby noxious substances
are rendered less harmful and are more easily excreted in urine.
Making the toxic substance inactive & more soluble so as to excrete out of
the body safely.
Mainly those substances thrown out of the body by kidneys
Major organ for Xenobiotic metabolism & for detoxification is Liver

4. Source of Toxins
Exogenous
Diet - additive
Drug - chemical
Abuse - toxins
Microbes.
Occupation - man made
Endogenous
Metabolism
Normal - urea, UA,
Bilirubin
Abnormal - Acetae, formate

5. Biotransformation of Toxins
The present concept is that the reactions
of xenobiotics occur in two phases
The overall purpose of these two phases
is to increase their water solubility and
thus facilitate their excretion from the
body.

7. Oxidation
Phase 1 Reactions
Reduction
Hydrolysis

8. A. OXIDATION
Oxidation
or
Hydroxylation

9. A. OXIDATION
A large number of foreign substances
are destroyed in the body by oxidation.
Aliphatic as well as aromatic alcohols
may be oxidised to corresponding
acids, probably via aldehyde formation.
In addition certain amines, anilides and
drugs also can undergo oxidation.
Reaction needs
• Cytochrome P450/Mono-
oxygenase
• Concentrated on smooth
ER of liver
• Heme containing enzyme

10. These reactions generally introduce a hydroxyl group into a
compound, making it more polar and preparing it for a subsequent
excretion.
The monooxygenases of the cytochrome P-450 type are the enzymes
that are involved in the metabolism of xenobiotics.
The monooxygenases catalyze the hydroxylation of various xenobiotics
using molecular oxygen as the source of oxygen and NADPH as a
reducing source.

11. Examples of oxidation
Oxidation of Aldehyde
Oxidized to corresponding acids also.
Oxidation of Alcohols
These are oxidized to corresponding acids.

12. Examples of oxidation
Detoxification of Amines:
These are oxidized to corresponding
acids.
Aromatic hydrocarbons:
These are oxidized to phenols or
phenolic compounds, which are then
conjugated with sulphuric & glutamic
acids.
Anilides:
These are oxidized to corresponding
phenols
Drugs:
Chloral is partly oxidized to trichloroacetic
acid, which excreted as its salts.
Sulfur compounds:
Organic sulfur is oxidized to sulfuric acid.

13. B. Reduction

14. B. Reduction
Certain aldehydes e.g., chloral, undergoes reduction to form corresponding
alcohol, which is then conjugated with D-glucuronic acid & excreted as
corresponding glucuronides.
Aromatic nitro compounds, e.g.,
p-nitrobenzaldehyde is reduced to
corresponding amines & excreted after
conjugation

15. Examples of Reduction

16. C. Hydrolysis

17. C. Hydrolysis
The hydrolysis of bonds -
ester, glycoside & amide.
Usually occurs in liver.
Enzymes

18. Thank you