A new perspective on the importance of glycine conjugation in the metabolism of aromatic acids
Date
2014Author
Badenhorst, Christoffel Petrus Stephanus
Erasmus, Elardus
Van der Sluis, Rencia
Nortje, Carla
Van Dijk, Alberdina Aike
Metadata
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A number of endogenous and xenobiotic organic acids are conjugated to glycine, in animals
ranging from mosquitoes to humans. Glycine conjugation has generally been assumed to be a
detoxification mechanism, increasing the water solubility of organic acids in order to facilitate
urinary excretion. However, the recently proposed glycine deportation hypothesis states that
the role of the amino acid conjugations, including glycine conjugation, is to regulate systemic
levels of amino acids that are also utilized as neurotransmitters in the central nervous systems
of animals. This hypothesis is based on the observation that, compared to glucuronidation,
glycine conjugation does not significantly increase the water solubility of aromatic acids. In this
review it will be argued that the major role of glycine conjugation is to dispose of the end
products of phenylpropionate metabolism. Furthermore, glucuronidation, which occurs in the
endoplasmic reticulum, would not be ideal for the detoxification of free benzoate, which has
been shown to accumulate in the mitochondrial matrix. Glycine conjugation, however,
prevents accumulation of benzoic acid in the mitochondrial matrix by forming hippurate,
a less lipophilic conjugate that can be more readily transported out of the mitochondria.
Finally, it will be explained that the glycine conjugation of benzoate, a commonly used
preservative, exacerbates the dietary deficiency of glycine in humans. Because the resulting
shortage of glycine can negatively influence brain neurochemistry and the synthesis of
collagen, nucleic acids, porphyrins, and other important metabolites, the risks of using
benzoate as a preservative should not be underestimated
URI
http://hdl.handle.net/10394/15904https://www.tandfonline.com/doi/full/10.3109/03602532.2014.908903
https://doi.org/10.3109/03602532.2014.908903