BIOCHEMICAL REACTION

PKF
2014

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The Fate of a Drug
DOSE

Pharmaceutics
ABSORPTION
MOST TISSUES
NONSPECIFIC
BINDING
PLASMA
PROTEIN
BOUND FREE DISTRIBUTION

BIOPHASE
ELIMINATION RECEPTOR
BINDING
METABOLISM RENAL
EXCRETION
EFFECT

Pharmacokinetics Pharmacodynamics
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Drug Metabolism

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Biochemical Reactions
Chemical reactions associated with
biological processes
Often involve a combination of more than
one type of reaction
Four main types of reactions:
Neutralization
Oxidation-Reduction
Condensation
Hydrolysis
Acylation

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Acid-Base Reactions
Acid: produces H+ ions in water
pH value less than 7
Base: produces OH- ions in water or accepts H+
ions
pH value more than 7
Neutralization Reaction: interaction of an acid
and a base to form a salt (an ionic compound)
and water

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 Neutralization Reaction
Necessary to maintain a constant pH state within
the body
Buffers: resist changes in pH
Release H+ ions when fluid is too basic
Take up H+ ions when fluid is too acidic

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Oxidation-Reduction Reactions
Involves the transfer of electrons
Oxidation: loss of electrons
Reduction: gain of electrons
Electrons are highly reactive and dont
exist on their own in cells
If oxidation occurs to one molecule in the cell,
reduction must immediately to another
molecule
The entire reaction is often called a
redox reaction

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 Condensation Reactions
Involved in the assembly of all Also known
as
four types of macromolecules dehydration
An H atom is removed from a synthesis
functional group on one molecule,
and an OH group is removed from
another molecule
Result: a larger molecule + water
(water out, monomer in)

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 Hydrolysis Reactions
Involved in the breakdown of
macromolecules into their
monomers
Water is added to break the
bonds between monomers
(water in, monomer out)
H from the water is added to
one molecule, and the OH
group is added to the adjacent
monomer
Covalent bond between
monomers breaks to form two
smaller molecules
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 Uses hydrolase class of enzymes : Esterase
Enzyme or Amidase Enzyme
Removing water to create larger molecules
Adding water to split larger molecules into smaller
molecules

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1- Esterase enzymes:
Usually present in plasma and various tissues, are nonspecific and
catalyze de-esterification. Hydrolysis of nonpolar esters into two polar
and more water soluble compounds (i.e. acid and alcohol).

O O
CH3 C OR + H2O CH3 C OH + ROH
Ester of acetic acid Acetic acid Alcohol

Esterases are responsible for converting many prodrugs into

their active forms.
A classical example of ester hydrolysis is the metabolic
conversion of aspirin (acetylsalicylic acid) to salicylic acid
and acetic acid. COOH COOH
OCOCH3 OH
H2O + CH3COOH
Acetic acid
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2-Amidase enzymes:
It is the hydrolysis of amides into amine and acid and this is
called Deamination.Deamination occurs primarily in the liver.

O O
NH2 C R + H2O R C OH + NH3
Amide Water Acid Ammonia

Amide drugs are more resistant to hydrolysis (or they are

not hydrolyzed until they reach the liver) than ester drugs
which they are susceptible to plasma esterase.
The duration of actions of ester drugs are less than the
amide analogues.
Example:
Procaine (ester type) injection or topical is usually shorter
acting than its amide analogue procainamide administered
similarily.
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Acylation

What is an acylation reaction?

What is the nucleophilic addition-elimination

mechanism for acylation reactions?

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 O
The acyl group: R C

Acylation is the process by which

the acyl group is introduced into
another molecule.
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Think of examples of types of compounds
containing the acyl group.

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 O
R C
Z

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 O O O

R C X + H O R' R C O R' + HX X = Cl or O C R'

ester

O H O H O
+ -
R C Cl + 2 H N R' R C N R' + NH3R' X X = Cl or O C R'

amide

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 Addition-elimination mechanism
_
O O O O
- +
+ - Cl + -H
R C R C O R' R C O R' R C O R'

Cl Cl H H
H O R'

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 Addition-elimination mechanism
_
O O H O H O H
- +
+ - Cl + -H
R C R C N R' R C N R' R C N R'

Cl Cl H H
H N R'

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