Amino acid conjugation: contribution to the metabolism and toxicity of xenobiotic carboxylic acids

Knights, Kathleen M.; Sykes, Matthew J.; Miners, John O.

doi:10.1517/17425255.3.2.159

Cited by 94 publications

(83 citation statements)

References 54 publications

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“…Bile acids are also conjugated by a similar sequence of reactions involving a microsomal cholyl-CoA synthetase and a cytosolic enzyme bile acid-CoA: amino acid N-acyltransferase (Falany et al, 1994). In relation to xenobiotic carboxylic acids, amino acid conjugation involves enzymes located principally in the mitochondria of liver and kidney while conjugation of bile acids is extramitochondrial, involving enzymes located in the endoplasmic reticulum and peroxisomes (Reilly et al, 2007;Knights et al, 2007). Glycine and glutamate appear to be the most common acceptors of amino acids in mammals.…”

Section: Amino Acid Conjugation Reactionsmentioning

confidence: 99%

Phase II Drug Metabolism

Jančová¹,

Siller²

2012

Topics on Drug Metabolism

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Section: Amino Acid Conjugation Reactionsmentioning

confidence: 99%

Phase II Drug Metabolism

Jančová¹,

Siller²

2012

Topics on Drug Metabolism

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“…GLYAT is involved in the detoxification of endogenous and exogenous xenobiotic acyl-CoAs and in the metabolism of short chain fatty acids in mammals (for review, see Ref. 18). hGLYATL2 conjugates long chain acyl-CoAs such as oleoyl-CoA, stearoyl-CoA, and arachidonoyl-CoA to glycine (14), whereas the substrate(s) for hGLYATL1 and hGLYATL3 remains unidentified.…”

Section: Lysine 19 Of Glyatl2 Is a Conserved Residue In Severalmentioning

confidence: 99%

Reversible Lysine Acetylation Regulates Activity of Human Glycine N-Acyltransferase-like 2 (hGLYATL2)

Waluk

Sucharski

Sípos

et al. 2012

Journal of Biological Chemistry

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Background: Lysine acetylation is a major post-translational modification of proteins. Results: Human glycine N-acyltransferase-like 2 is regulated by acetylation/deacetylation of lysine 19. Conclusion: Reversible lysine acetylation is important in regulating the activity and function of human glycine N-acyltransferases. Significance: Our study links post-translational modification of proteins with the production of lipid signaling molecules, the N-acyl glycines.

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“…Like the shorter chain N-acetyl and N-isovaleroyl amino acids, the major function of these longer chain amino acid conjugates would appear to be in the detoxification and excretion of xenobiotic carboxylates [7]. Glycine conjugation is particularly important in detoxification and elimination, as a careful analysis of the metabolism of most xenobiotic carboxylates reveals at least a trace of the corresponding N-acylglycine conjugate [67]. In fact, the list of N-acylglycines shown in Table 1 is incomplete as glycine conjugates of many other carboxylates also have been reported [67,68].…”

Section: N-acylamino Acidsmentioning

confidence: 99%

Biosynthesis, degradation and pharmacological importance of the fatty acid amides

Farrell

Merkler

2008

Drug Discovery Today

115

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The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologically-occurring fatty acid amides. In this review, we will outline which fatty acid amides have been isolated from mammalian sources, detail what is known about how these molecules are made and degraded in vivo, and highlight their potential for the development of novel therapeutics. Keywords N-acylamino acid; N-acyldopamine; N-acylethanolamine; primary fatty acid amide; N-acylamideThe fatty acid amide bond has long been recognized in nature, being important in the structure of the ceramides [1] and the sphingolipids [2]. The first non-sphingosine based fatty acid amide isolated from a natural source was N-palmitoylethanolamine from egg yolk in 1957 [3]. Interest in the N-acylethanolamines (NAEs) dramatically increased upon the identification of Narachidonoylethanolamine (anandamide) as the endogenous ligand for the cannabinoid receptors in the mammalian brain [4]. It is now known that a family of NAEs is found in the brain and in other tissues [5,6].In addition to the NAEs, other classes of fatty acid amides have been characterized, namely the N-acylamino acids (NAAs) [7], the N-acyldopamines (NADAs) [8] and the primary fatty acid amides (PFAMs) [9,10] (Figure 1). Relative to NAEs, much less is currently known about the NAAs, the NADAs and the PFAMs, except that they are found in biological systems. The goal of this review is to summarize the current state of knowledge regarding the different classes of endogenous fatty acid amides and highlight their potential for drug discovery (see refs. [11-13] for earlier reviews) © 2008 Elsevier Ltd. All rights reserved.Corresponding author: Merkler, D.J (E-mail: merkler@cas.usf.edu) phone 813-974-3579; fax 813-974-1733. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Teaser SentenceFatty acid amides are a family of mammalian bioactive compounds. These molecules and the enzymes involved in their metabolism provide an opportunity to develop new drugs to treat human disease. -palmitoyl-, N-stearoyl-and N-oleoylethanolamine [5,11], each compromising ≥25% of total brain NAEs. Other less abundant NAEs found in the brain are anandamide, N-linoleoyl-, N-linolenoyl-, N-dihomo-γ-linolenoyl-and N-docosatetraenoylethanolamine [11]. In addition to the brain, the NAEs are widespread in the peripheral tissues [5]. The mos...

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Amino acid conjugation: contribution to the metabolism and toxicity of xenobiotic carboxylic acids

Cited by 94 publications

References 54 publications

Phase II Drug Metabolism

Phase II Drug Metabolism

Reversible Lysine Acetylation Regulates Activity of Human Glycine N-Acyltransferase-like 2 (hGLYATL2)

Biosynthesis, degradation and pharmacological importance of the fatty acid amides

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