2. Harm DNA & RNA
Enzymatic
Chemical
Reactions
Less harmful &
Water soluble
More toxic Chemical
Excreted in. Urine
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XENOBIOTICS
Foreign molecule of
different origin
Drugs, Food Additives, Pesticides
3. DETOXIFICATION
Biochemical changes proceeding in the body which
converts molecules foreign to the body to compounds that
are more readily excretable and less harmful
Biochemical process of converting foreign/toxic compound into less
toxic & easily excretable compound is k/as detoxification.
5. MAIN PURPOSE: converts toxic
substance into MORE POLAR
compounds
MAIN SITE: LIVER
Two Phases:
Phase 1
Conversion in to more soluble
compounds.
Processes:
Major: Hydroxylation
Minor: Deamination,
Desulfiration, Epoxidation &
Prooxygenation
Phase 2
already hydroxylated
products
Conjugation Reactions
( Glutathione, Glycine, Glucoronic Acid)
↑↑ solubility, ↑↑ Polar
Excreted in urine
6. Phase: 1
• Increases Solubility
• Addition of special function groups to further divert them second
phase
• Enzyme:
• Cyto P450 : Can Detoxify endo & Exogenous products.
• Monooxygenase Enzyme:
OXIDATION:
Methyl alcohol formic acid
Benzyl alcohol benzoic acid
Chloral (hypnotic) TCA Cyto P450
7. REDUCTION:
Aldehyde alcohol
Picric acid picramic acid
P-nitro benzene p-amino benzene
Paranitrophenol Para amino phenol
HYDROLYSIS: Toxic molecule broken in to small molecule
X-Y. + H2O X -OH + Y-H
Atropine tropic acid + tropine
Digitalis aglycone + sugar
Aspirin salicylic acid + acetic acid
8. Phase: 2
• Converts hydroxylated products in to more polar one.
• Conjugating agents acts on already transformed xenobiotics.
1. GLUTATHIONE: ( Glu-Cyst- Gly)
Alkyl/ Aryl / Halide
aliphatic halides
Cysteine Alken
carcinogenic Epoxide
polycyclic hydrocarbons
Detoxification of Cyclophosphamide
9. CONJUGATION REACTIONS
2. GLYCINE:
Cholic acid + Glycine Glycocholic acid
Benzoic acid + Glycine Hippuric acid
Nicotinic acid + Glycine Nicotinuric acid
LFT: Load of sod benzoate is given to patient and
hippuric acid estimated in urine
3. GLUTAMINE:
Phenylacetic acid + Glu Phenylacetic.glu acid
10. 3. GLUCURONIC ACID
Bilirubin + Glu acid Bil di glucoronide
Phenol + Glu acid Phenyl glucuronide
Benzoic acid + Glu acid Benzoly glucoronide
Morphine, Meprobomate, chloramphenicol, steroid hormones,
Acetalamino flourine
4. SULPHURIC ACID
PAPS in liver conjugates with cresol, indol, skatol and form etheral
sulphates
11. 4. Methylation: S- ADENOSYL METHIONINE (SAM)
Pyridine + SAM N- methyl pyridine
Nicotonic acid + SAM N-methyl NA
6. CYSTEINE
Acetyl cysteine conjugates with chloro, bromo and iodo benzene
mercapturic acid
5. ACETYLATION
Sulphanilamide +acetic acid acetyl sulphanilamide
PABA + acetyl CoA acetyl PABA
12. 1. PARA AMINO BENZOIC ACID
Hydroquinone and phenylarsenate (as poison) are detoxicated
as conjugates of PABA
Applications of Detoxification Reaction
2.THIOSULPHATES
Cyanide + Sodium thiosulphate
thiocyanate+ sodium sulphate
13. 3. BRITISH ANTILEWISITE (BAL)/ Dimercaprol
Lewisite(organarsenic Acid) & Hg,Au,Cd.
BAL
Active SH Enzyme Inactive SH Enzymes
inhibit many enzymes by attacking SH. BAL due to higher affinity for
them, withdraws them.
Lewisite: used in world war II a chemical warfare and BAL as antidote
14. 4. p- BROMOBENZENE
Selenium (Se) poisoning due to high feeding of soil products,
replaces sulfur in cysteine and methionine of the body tissue.
Selenium (Se) + p-bromobezene mercapturic acid
( excreted in urine)
15. Summary
• Difference between Detoxification & Biotransformation
• Two phases of the detoxification .
• Application of Detoxification
Question asked:
Define detoxification & Give any four examples of conjugation reactions?
Describe first phase of detoxification?
Editor's Notes
Food additive: Monosodium Glutamate, Citric Acid ( Used to keep fruit fresh) , Sunflower lecithin (coffe), Calcium Disodium EDTA( Maynees), Sorbic acid (wines), colur preservative , Antioxidants. Flavour enhancers, Emulsifier, stabilizers.
Bacterial metabolites: SCFA, Secondory bile acids, Acetaldehydes, Phenolic acids
MORE SOLUBLE IN AQUEOUS MEDIUM – INCREASES EXCRETION
DECREASES SOLUBILITY IN LIPID – DECREASES PERMIABILITY
Cyto P450 : Can Detoxify endo & Exogenous products. ( steroids/ Ecosanoids)
Monooxygenase Enzyme Adds only one of the two oxygen atoms.
Cyt P450: Enzyme mono-oxygenase detoxifies 50% of any drug (This hemoprotein enzyme system requires NADPH and is present in highest concentration in endoplasmic reticulum of microsomal fraction of liver and contains lecithin