The Biosynthesis and Metabolism of the N-Acylated Aromatic Amino Acids: N-Acylphenylalanine, N-Acyltyrosine, N-Acyltryptophan, and N-Acylhistidine.

Suzeeta Bhandari,David J Merkler,Kirpal S Bisht

doi:10.3389/fmolb.2021.801749

Suzeeta Bhandari, David J Merkler + Show 1 more

Open Access

https://doi.org/10.3389/fmolb.2021.801749

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Abstract

The fatty acid amides are a family of lipids composed of two chemical moieties, a fatty acid and a biogenic amine linked together in an amide bond. This lipid family is structurally related to the endocannabinoid anandamide (N-arachidonoylethanolamine) and, thus, is frequently referred to as a family of endocannabinoid-related lipids. The fatty acid amide family is divided into different classes based on the conjugate amine; anandamide being a member of the N-acylethanolamine class (NAE). Another class within the fatty acid amide family is the N-acyl amino acids (NA-AAs). The focus of this review is a sub-class of the NA-AAs, the N-acyl aromatic amino acids (NA-ArAAs). The NA-ArAAs are not broadly recognized, even by those interested in the endocannabinoids and endocannabinoid-related lipids. Herein, the NA-ArAAs that have been identified from a biological source will be highlighted and pathways for their biosynthesis, degradation, enzymatic modification, and transport will be presented. Also, information about the cellular functions of the NA-ArAAs will be placed in context with the data regarding the identification and metabolism of these N-acylated amino acids. A review of the current state-of-knowledge about the NA-ArAAs is to stimulate future research about this underappreciated sub-class of the fatty acid amide family.

Highlights

The fatty acid amides are a biologically important family of lipids resulting from a fatty acid and a biogenic amine linked together in an amide bond (Ni et al, 2021)
Knowledge of the N-acylated amino acids was generally limited to short-chain N-acyl amino acids (NA-AAs) because the N-acetylated derivatives of all the amino acids have been identified (Wishart et al, 2018) and specific short-chain NA-AAs are biomarkers for different metabolic diseases (Goldstein, 1963; Millington et al, 1991; Loots et al, 2005; Scolamiero et al, 2015)
We have identified N-arylalkylamine N-acyltransferases (AANATs) that accept long-chain acyl-CoA thioesters and arylalkylamines that are related to the aromatic amino acids, like histamine, phenethylamine, tyramine, and tryptamine, but these enzymes will not utilize the aromatic amino acids as substrates (Dempsey et al, 2014; Dempsey et al, 2015; Battistini et al, 2019)

Summary

Introduction

The fatty acid amides are a biologically important family of lipids resulting from a fatty acid and a biogenic amine linked together in an amide bond (Ni et al, 2021). A sub-class of the NA-AAs, the N-acyl aromatic amino acids (NA-ArAAs) are not broadly recognized, even by those interested in the endocannabinoid-related lipids, but several of the NAArAAs have been identified from a biological source.

Results

Conclusion