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Hello, my name is Kathleen Knights,
and I'm located in
the Department of Clinical Pharmacology at Flinders University, Adelaide Australia.
The title of my talk is "Amino Acid Conjugation: Mechanism and Enzymology".
This talk will start with a brief overview of the mechanism of amino acid conjugation.
In particular, the key enzymes involved,
the xenobiotic/medium-chain fatty acid:CoA ligases,
now referred to as acyl-CoA synthetases medium-chain or ACSMs.
And, the Acyl-CoA:glycine N-acyltransferases commonly referred to as GLYAT.
We will look briefly at conjugation in vivo,
and the talk will conclude with an overview of xenobiotic acyl-CoA toxicity.
History of amino acid conjugation starts with benzoic acid,
one of the oldest chemical preservatives permitted in
food in the United States, in about 1908.
The story begins however much earlier than that.
And by 1829, hipppuric acid had been isolated from horse urine.
In men, the first proof that benzoic acid was
metabolized to hippuric acid came from the work of Keller in 1842.
Keller actually had analyzed his own urine after taking benzoic acid.
Undoubtedly, conjugation of benzoic acid to
the glycine to yield hippuric acid or benzoylglycine,
laid the foundations for the continued interest
in conjugation reactions in drug metabolism.
Unfortunately, advances in the field of amino acid conjugation
have been small in comparison to the field of glucuronidation.