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

**Authors:** Simone Fabbian, Beatrice Masciovecchio, Elisabetta Schievano, Gabriele Giachin

PMC · DOI: 10.1021/acsbiomedchemau.4c00140 · ACS Bio & Med Chem Au · 2025-03-15

## TL;DR

This study reveals a new product of fatty acid oxidation using NMR, suggesting a novel pathway in lipid metabolism.

## Contribution

Discovery of γ-oxidation products in fatty acid oxidation, indicating a new catalytic pathway.

## Key findings

- Identified (2E)-hexadecenoyl-CoA as the α-β-dehydrogenation product.
- Discovered E and Z stereoisomers of 3-hexadecenoyl-CoA as γ-oxidation products.
- Suggested a regulatory role for ACAD9 and VLCAD in fatty acid metabolism.

## 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.

## Linked entities

- **Proteins:** ACADVL (acyl-CoA dehydrogenase very long chain), ACAD9 (acyl-CoA dehydrogenase family member 9)
- **Chemicals:** palmitoyl-CoA (PubChem CID 644109), (2E)-hexadecenoyl-CoA (PubChem CID 16061165)

## Full-text entities

- **Genes:** ACAD9 (acyl-CoA dehydrogenase family member 9) [NCBI Gene 28976] {aka MC1DN20, NPD002}, ACADVL (acyl-CoA dehydrogenase very long chain) [NCBI Gene 37] {aka ACAD6, LCACD, VLCAD}
- **Diseases:** mitochondrial diseases (MESH:D028361)
- **Chemicals:** (2E)-hexadecenoyl-CoA (-), fatty acid (MESH:D005227), palmitoyl-CoA (MESH:D010171), Lipid (MESH:D008055)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12006827/full.md

## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC12006827/full.md

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Source: https://tomesphere.com/paper/PMC12006827