This reaction also occurs to a limited extent because of limited availability of amino acids.
CONJUGATION WITH ALPHA AMINO ACIDS
This reaction also occurs to a limited extent
because of limited availability of amino acids.
The reaction occurs in two steps:
1. Activation of carboxylic acid drug substrate
with ATP and coenzyme A (CoA) to form an
acyl CoA intermediate. Thus, the reaction is a contrast of glucuronidation and
sulphation where the donor coenzyme is activated and not the substrate.
2. Acylation of
the -amino acid by the acyl CoA in presence of enzyme N-acyl transferase.
The reaction is summarized below.
where R’ = -CH2- (if glycine) or
>CH-CH2-CH2-CONH2 (if glutamine)
Conjugation occurs commonly with glycine. Glutamine
conjugation occurs to a lesser extent. Conjugation with other amino acids like
aspartic acid, serine and taurine is still uncommon. The substrate is generally
an acid (aromatic in particular) and the reaction product is an amide.
Examples of drugs forming glycine or glutamine
conjugates are:
Aliphatic acids e.g.
isopropoxyacetic acid
Alicyclic acids e.g. cholic acid
Aryl acids e.g. salicylic acid
Arylacetic acids e.g.
phenylacetic acid
Heterocyclic aryl acids e.g.
nicotinic acid.
Amino acid conjugation occurs extensively in the
liver mitochondria and thus the reaction can be used to estimate hepatic function. The diagnostic marker
used is benzoic acid which on conjugation with glycine yields hippuric acid.
Hippuric acid is rapidly excreted in urine. Thus, the rate and extent of
urinary excretion of hippuric acid following oral or i.v. administration of
benzoic acid indicates functioning of liver. A decreased output indicates
hepatic disorder.
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