Phthalate esters enhance quinolinate production by inhibiting alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD), a key enzyme of the tryptophan pathway

Toxicological Sciences : an Official Journal of the Society of Toxicology
Tsutomu FukuwatariKatsumi Shibata

Abstract

Tryptophan is metabolized to alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS) via 3-hydroxyanthranilate (3-HA). ACMS decarboxylase (ACMSD) directs ACMS to acetyl CoA; otherwise ACMS is non-enzymatically converted to quinolinate (QA), leading to the formation of NAD and its degradation products. Thus, ACMSD is a critical enzyme for tryptophan metabolism. Phthalate esters have been suspected of being environmental endocrine disrupters. Because of the structural similarity of phthalate esters with tryptophan metabolites, we examined the effects of phthalate esters on tryptophan metabolism. Phthalate esters containing diets were orally given to rats and the urinary excreted tryptophan metabolites were quantified. Of the phthalate esters with different side chains tested, di(2-ethylhexyl)phthalate (DEHP) and its metabolite, mono(2-ethylhexyl)phthalate (MEHP), most strongly enhanced the production of QA and degradation products of nicotinamide, while 3-HA was unchanged. This pattern of metabolic change led us to assume that these esters lowered ACMSD protein or its activity. Although DEHP could not be tested because of its low solubility, MEHP reversibly inhibited ACMSD from rat liver and mouse kidney, and also the recomb...Continue Reading

Citations

Aug 21, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jose Felix Martí-MassóCoro Paisán-Ruiz
Jan 29, 2016·Neuropharmacology·Elena Y Bryleva, Lena Brundin
Feb 9, 2013·Bioscience, Biotechnology, and Biochemistry·Katsumi ShibataTsutomu Fukuwatari
Jul 13, 2014·Archives of Environmental Contamination and Toxicology·Marc RigdenJianli Jiao
Jun 24, 2016·Pharmaceutical Patent Analyst·Hermann Am Mucke
Dec 22, 2009·Molecular BioSystems·Suresh SelvarasuDong-Yup Lee
Aug 8, 2013·International Journal of Tryptophan Research : IJTR·Tsutomu Fukuwatari, Katsumi Shibata
Jan 1, 2013·Nutrition and Metabolic Insights·Katsumi ShibataTsutomu Fukuwatari
Dec 17, 2008·Dalton Transactions : an International Journal of Inorganic Chemistry·Jessica GätjensVincent L Pecoraro
Jul 4, 2017·Journal of Parkinson's Disease·Dolores VilasCoro Paisán-Ruiz
Jan 1, 2009·International Journal of Tryptophan Research : IJTR·R S GrantG A Smythe
Apr 26, 2013·The Journal of Nutrition·Chiaki HiratsukaKatsumi Shibata
Sep 30, 2017·Annual Review of Pharmacology and Toxicology·Vincenzo SorrentinoJohan Auwerx
May 21, 2019·Egyptian Journal of Basic and Clinical Pharmacology·Abdulla Abu-Bakr Badawy
Apr 21, 2020·Drug Design, Development and Therapy·Ting WangPeng Xie
Nov 11, 2019·Experimental Gerontology·Abdulla A-B Badawy

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