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Biotransformation
1.
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
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.
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
11.
12. Most common type of metabolic reaction
Drug + UDPGA drug
glucuronide + UDP
Glucuronyl transferase
excreted