Hidden β-γ Dehydrogenation Products in Long-Chain Fatty Acid Oxidation Unveiled by NMR: Implications on Lipid Metabolism

IF 3.8 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

ACS Bio & Med Chem Au Pub Date : 2025-03-15 DOI:10.1021/acsbiomedchemau.4c0014010.1021/acsbiomedchemau.4c00140

Simone Fabbian, Beatrice Masciovecchio, Elisabetta Schievano and Gabriele Giachin*,

引用次数: 0

Abstract

We present a comprehensive analysis of the initial α,β-dehydrogenation step in long-chain fatty acid β-oxidation (FAO). We focused on palmitoyl-CoA oxidized by two mitochondrial acyl-CoA dehydrogenases, very-long-chain acyl-CoA dehydrogenase (VLCAD) and acyl-CoA dehydrogenase family member 9 (ACAD9), both implicated in mitochondrial diseases. By combining MS and NMR, we identified the (2E)-hexadecenoyl-CoA as the expected α-β-dehydrogenation product and also the E and Z stereoisomers of 3-hexadecenoyl-CoA: a “γ-oxidation” product. This finding reveals an alternative catalytic pathway in mitochondrial FAO, suggesting a potential regulatory role for ACAD9 and VLCAD during fatty acid metabolism.

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核磁共振揭示长链脂肪酸氧化中隐藏的β-γ脱氢产物：对脂质代谢的影响

我们对长链脂肪酸β-氧化（FAO）中α，β-脱氢的初始步骤进行了全面的分析。我们重点研究了两种线粒体酰基辅酶a脱氢酶，超长链酰基辅酶a脱氢酶（VLCAD）和酰基辅酶a脱氢酶家族成员9 （ACAD9）氧化棕榈酰辅酶a，这两种酶a都与线粒体疾病有关。结合质谱和核磁共振，我们确定了(2E)-十六烷基辅酶a是预期的α-β-脱氢产物，3-十六烷基辅酶a的E和Z立体异构体是“γ-氧化”产物。这一发现揭示了线粒体FAO的另一种催化途径，表明ACAD9和VLCAD在脂肪酸代谢过程中具有潜在的调节作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Bio & Med Chem Au 药物、生物、化学-

CiteScore

4.10

自引率

0.00%

发文量

期刊介绍： ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.