Document Detail


Dog bites man or man bites dog? The enigma of the amino acid conjugations.
MedLine Citation:
PMID:  22227274     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The proposition posed is that the value of amino acid conjugation to the organism is not, as in the traditional view, to use amino acids for the detoxication of aromatic acids. Rather, the converse is more likely, to use aromatic acids that originate from the diet and gut microbiota to assist in the regulation of body stores of amino acids, such as glycine, glutamate, and, in certain invertebrates, arginine, that are key neurotransmitters in the central nervous system (CNS). As such, the amino acid conjugations are not so much detoxication reactions, rather they are homeostatic and neuroregulatory processes. Experimental data have been culled in support of this hypothesis from a broad range of scientific and clinical literature. Such data include the low detoxication value of amino acid conjugations and the Janus nature of certain amino acids that are both neurotransmitters and apparent conjugating agents. Amino acid scavenging mechanisms in blood deplete brain amino acids. Amino acids glutamate and glycine when trafficked from brain are metabolized to conjugates of aromatic acids in hepatic mitochondria and then irreversibly excreted into urine. This process is used clinically to deplete excess nitrogen in cases of urea cycle enzymopathies through excretion of glycine or glutamine as their aromatic acid conjugates. Untoward effects of high-dose phenylacetic acid surround CNS toxicity. There appears to be a relationship between extent of glycine scavenging by benzoic acid and psychomotor function. Glycine and glutamine scavenging by conjugation with aromatic acids may have important psychosomatic consequences that link diet to health, wellbeing, and disease.
Authors:
Diren Beyoğlu; Robert L Smith; Jeffrey R Idle
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-29
Journal Detail:
Title:  Biochemical pharmacology     Volume:  83     ISSN:  1873-2968     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-03-27     Completed Date:  2012-05-14     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1331-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Hepatology Research Group, Department of Clinical Research, Faculty of Medicine, University of Bern, Murtenstrasse 35, 3010 Bern, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / blood,  cerebrospinal fluid,  metabolism*,  urine
Animals
Blood-Brain Barrier
Humans
Rats
Grant Support
ID/Acronym/Agency:
U19 AI067773-07/AI/NIAID NIH HHS; Z99 CA999999/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids
Comments/Corrections

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