Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5823927 | Biochemical Pharmacology | 2012 | 9 Pages |
Abstract
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.
Keywords
mGluRNMDAREAATEAAAmino acid conjugationECFLPIGLNIAGECTIAAgPb4-Nitrobenzoic acidPAA2-Furoic acidArginineexcitatory amino acidArg4-Aminobenzoic acidInhibitory amino acidPhenylacetic acidHippuric acidglutamic acidBenzoic acidTaurineexcitatory amino acid transporterTauElectroconvulsive therapyCNSBBBcentral nervous systemLysinuric protein intoleranceBlood-brain barrierextracellular fluidCSFCerebrospinal fluidhigh-performance liquid chromatographyHPLCGluglutamineGlyGlycineN-methyl-d-aspartate receptorMetabotropic glutamate receptorNaPBA
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Pharmacology
Authors
Diren BeyoÄlu, Robert L. Smith, Jeffrey R. Idle,