1

Biochemistry
Drug metabolism (phase I & II)

Some drugs directly

enter phase ii metabolism

Drug phasel oxidation, reduction phase II conjugation products

and/or hydrolysis

Following phase I the conjugated drug

drug may be activates is usually inactive.
b Unchanged . or most often ,
inactivated

Phase II

Pathway Active moiety Enzyme Example

Glucouronidation Glucouronic acid Glucouronyl -OH , -NR2

transferase -COOH , -SH

SO4 Conjugation PAPS Sulfatransferase -OH , amyl Amin

Phospho adenosine -NHNH2
5 phospho SO4
‫ى‬
Acetic acid Conj. Glycine/ glutamine N- acyl transferase - COOH
+active drug (drug+ Co
ASH ) co enz A

Glutathione conj. GSH Glutathione -X , epoxide

(keep cell S-transferase
integrity)

Methyl conj SAM Methyl transferase -OH , SH , NH2

S-adenosyl methionine

A
Acetylation conj. Acetyl co A N- Acetyl transferase NH2 , NHNH2 ,
SO2NH2 , CONH2

Edition 2015 Cell:+1(571)699 4550

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Table phase II biotransformation

-Bio activation: prodrug active drug in the body

-usually metabolites have low O/W partition coeff.

Decrease oil sol. Increase water sol.

-functional group metabolism occur in phase I .

- O2N _ N=N - OH -NO2 reduction

-AZO reduction
-OH conjugation

Benzodiazepines:

X=NO2 Metabolized by NO2 reduction

Imipramine (TCA) metabolized by hydroxylation terminally then conjugation with glucouronic acid

-local anesthetic metabolized by

If ester (Procaine): de esterification in plasma & tissues

Amide (Lidocaine): de amidation in liver (so long acting)

-amphetamine metabolism: oxidative de amination phase I

Citric acid cycle end product is 1 ATP, 3 NADH, 2 CO2 and 1 H2O (Creb’s cycle)

Edition 2015 Cell:+1(571)699 4550