2.  Biochemical alteration of chemicals such as (but not
limited to) nutrients, amino acids, toxins, and drugs
in the body
 It is also needed to render nonpolar compounds
polar so that they are not reabsorbed in renal
tubules and are excreted.
 The body typically deals with a foreign compound
(DRUGS) by making it more water-soluble, to
increase the rate of its excretion through the urine

3.  Site : usually liver
 Enzymes:

4. MICROSOMAL ENZYMES
 A group of enzymes
associated with a certain
particulate fraction of liver
homogenate.
 These are a mixed function
oxidase system or
monooxygenases.
 These requires NADPH and
oxygen.
NON MICROSOMAL ENZYMES
 These are present in the
cytoplasm and
mitochondria of hepatic
cells as well as in other
tissues including plasma.
The 2 most imp.
Microsomal
enzymes:
1. NADPH cyt.
P450 reductase
2. Cut. P450

5. Phase I
• Includes oxidative, reductive, and hydrolytic reactions.
• In these type of reactions, a polar group is either introduced or
unmasked, so the drug molecule becomes more water-soluble
and can be excreted.
• Reactions are non-synthetic in nature and in general produce a
more water-soluble and less active metabolites
Phase II
• These reactions involve covalent attachment of small polar
endogenous molecule such as glucuronic acid, sulfate, or
glycine to form water-soluble compounds.
• This is also known as a conjugation reaction.
• The final compounds have a larger molecular weight.

7.  Oxidation
 Reduction
 Hydrolysis

8.  Process of addition of oxygen or removal of
hydrogen from a drug molecule.
• Phenytoin hydroxyphenytoinhydroxylation
• Codeine  morphinedealkylation
• Cimetidine  cimetidine
sulfoxideS-oxidation
• Amphetamine
benzylmethylketonedeamination

9.  Addition of hydrogen or removal of oxygen
from a drug molecule.
 Nitro reduction :
chloramphenicol  arylamine
 Keto reduction:
cortisone  hydrocortisone

10.  Process where a drug molecule is split by the
addition of a molecule of water.
 Both microsomal and non-microsomal
enzymes maybe involved.
 Eg: acetylcholine+ H2O  choline + acetic
acid

12.  Most common type of metabolic reaction
 Drug + UDPGA drug
glucuronide + UDP
Glucuronyl transferase
excreted

13. Glutathione –s –
transferase

14. Enzyme : sulfotransferases