Cited by 303Lipid metabolism and biosynthesisMetabolism and Genetic DisordersFatty Acid Research and Health

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Metabolism of Very Long-Chain Fatty Acids: Genes and Pathophysiology

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Sassa, Takayuki, Kihara, Akio·2014·Biomolecules & Therapeutics

DOI 10.4062/biomolther.2014.017PMC PMC3975470

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Abstract

Fatty acids (FAs) are highly diverse in terms of carbon (C) chain-length and number of double bonds. FAs with C>20 are called very long-chain fatty acids (VLCFAs). VLCFAs are found not only as constituents of cellular lipids such as sphingolipids and glycerophospholipids but also as precursors of lipid mediators. Our understanding on the function of VLCFAs is growing in parallel with the identification of enzymes involved in VLCFA synthesis or degradation. A variety of inherited diseases, such as ichthyosis, macular degeneration, myopathy, mental retardation, and demyelination, are caused by mutations in the genes encoding VLCFA metabolizing enzymes. In this review, we describe mammalian VLCFAs by highlighting their tissue distribution and metabolic pathways, and we discuss responsible genes and enzymes with reference to their roles in pathophysiology.

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Fig. 1. Human FA elongation pathways. The FA elongation pathways of SFAs, MUFAs and PUFAs are illustrated. ELOVL isozymes (E1-E7) responsible for each elongation step are indicated. Parentheses denote ELOVLs that exhibit weak activity toward the indicated substrates. Δ5, Δ6 and Δ9 represent Δ5-, Δ6- and Δ9-desaturase, respectively. FA: fatty acid; SFA: saturated FA; MUFA: monounsaturated FA; PUFA: polyunsaturated FA.CC BY-NC · PubMed Central

Fig. 2. Mammalian FA elongation cycle. The FA elongation cycle and enzymes involved in each step are illustrated. In each cycle, acyl-CoA incorporates two carbon units from malonyl-CoA.CC BY-NC · PubMed Central

Fig. 3. FA compositions of SM. FA compositions of SM in indicated mouse tissues determined by liquid chromatography-mass spectrometry analysis are illustrated. SM: sphingomyelin; BAT: brown adipose tissue; WAT: white adipose tissue.CC BY-NC · PubMed Central

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Hou, Z., Shi, F., Ge, S., Tao, J., Ren, L., Wu, H., & Zong, S. (2021) · Figshare · doi:10.6084/m9.figshare.14227909
Additional file 3 of Comparative transcriptome analysis of the newly discovered insect vector of the pine wood nematode in China, revealing putative genes related to host plant adaptation
Hou, Z., Shi, F., Ge, S., Tao, J., Ren, L., Wu, H., & Zong, S. (2021) · Figshare · doi:10.6084/m9.figshare.14227891
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Additional file 1 of Comparative transcriptome analysis of the newly discovered insect vector of the pine wood nematode in China, revealing putative genes related to host plant adaptation
Hou, Z., Shi, F., Sixun, G., Tao, J., Ren, L., Wu, H., & Zong, S. (2021) · Figshare · doi:10.6084/m9.figshare.14227885
Additional file 6 of Comparative transcriptome analysis of the newly discovered insect vector of the pine wood nematode in China, revealing putative genes related to host plant adaptation
Hou, Z., Shi, F., Sixun, G., Tao, J., Ren, L., Wu, H., & Zong, S. (2021) · Figshare · doi:10.6084/m9.figshare.14227900
Additional file 11 of Comparative transcriptome analysis of the newly discovered insect vector of the pine wood nematode in China, revealing putative genes related to host plant adaptation
Hou, Z., Shi, F., Sixun, G., Tao, J., Ren, L., Wu, H., & Zong, S. (2021) · Figshare · doi:10.6084/m9.figshare.14227876
Additional file 2 of Comparative transcriptome analysis of the newly discovered insect vector of the pine wood nematode in China, revealing putative genes related to host plant adaptation
Hou, Z., Shi, F., Sixun, G., Tao, J., Ren, L., Wu, H., & Zong, S. (2021) · Figshare · doi:10.6084/m9.figshare.14227888
Additional file 5 of Comparative transcriptome analysis of the newly discovered insect vector of the pine wood nematode in China, revealing putative genes related to host plant adaptation
Hou, Z., Shi, F., Sixun, G., Tao, J., Ren, L., Wu, H., & Zong, S. (2021) · Figshare · doi:10.6084/m9.figshare.14227897
Additional file 13 of Comparative transcriptome analysis of the newly discovered insect vector of the pine wood nematode in China, revealing putative genes related to host plant adaptation
Hou, Z., Shi, F., Sixun, G., Tao, J., Ren, L., Wu, H., & Zong, S. (2021) · Figshare · doi:10.6084/m9.figshare.14227882
Additional file 8 of Comparative transcriptome analysis of the newly discovered insect vector of the pine wood nematode in China, revealing putative genes related to host plant adaptation
Hou, Z., Shi, F., Sixun, G., Tao, J., Ren, L., Wu, H., & Zong, S. (2021) · Figshare · doi:10.6084/m9.figshare.14227906
Additional file 4 of Comparative transcriptome analysis of the newly discovered insect vector of the pine wood nematode in China, revealing putative genes related to host plant adaptation
Hou, Z., Shi, F., Sixun, G., Tao, J., Ren, L., Wu, H., & Zong, S. (2021) · Figshare · doi:10.6084/m9.figshare.14227894
Additional file 10 of Comparative transcriptome analysis of the newly discovered insect vector of the pine wood nematode in China, revealing putative genes related to host plant adaptation
Hou, Z., Shi, F., Sixun, G., Tao, J., Ren, L., Wu, H., & Zong, S. (2021) · Figshare · doi:10.6084/m9.figshare.14227873
Additional file 7 of Comparative transcriptome analysis of the newly discovered insect vector of the pine wood nematode in China, revealing putative genes related to host plant adaptation
Hou, Z., Shi, F., Sixun, G., Tao, J., Ren, L., Wu, H., & Zong, S. (2021) · Figshare · doi:10.6084/m9.figshare.14227903
Additional file 12 of Comparative transcriptome analysis of the newly discovered insect vector of the pine wood nematode in China, revealing putative genes related to host plant adaptation
Hou, Z., Shi, F., Sixun, G., Tao, J., Ren, L., Wu, H., & Zong, S. (2021) · Figshare · doi:10.6084/m9.figshare.14227879
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Autosomal recessive ELOVL1-related disorder presenting with severe neonatal cholestasis: A novel clinical feature?
Tsai, A. C., Lee, H.-T., Sanchez, B., Huang, Y.-R., Krysinski, S., Zalan, A., & Falsey, E. (2026) · Molecular Genetics and Metabolism Reports · doi:10.1016/j.ymgmr.2026.101305
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Chehimi, M. (2018) · theses.fr (ABES) · doi:10.70675/2320b59az87a8z4993zac3dz9d7027404d96
Effets des acides gras ω-3 sur l'inflammation cérébro-vasculaire associée à la maladie d'Alzheimer et aux angiopathies amyloïdes cérébrales
Hur, J. (2017) · theses.fr (ABES) · doi:10.70675/74388921za6fcz4e1ez8033z6d776311f983
Altérations lipidiques et homéostatiques dans les tissus nerveux associées au vieillissement et à des dérégulations métaboliques : implication du microbiote intestinal et de l’autophagie
Albouery, M. (2020) · theses.fr (ABES) · doi:10.70675/3e190ceczf22dz44b0z936cz6c92f9f5309f
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Authors: Sassa, T., & Kihara, A.
Affiliations: Hokkaido University (JP)
Corresponding author: Kihara, Akio
ORCID: Sassa, Takayuki
Kihara, Akio
Venue: Biomolecules & Therapeutics
Publisher: The Korean Society of Applied Pharmacology
Published: 2014-03-31
Volume: 22
Issue: 2
Pages: 83-92
ISSN: 1976-9148 (ISSN-L)
2005-4483
DOI: 10.4062/biomolther.2014.017
PMC: PMC3975470
OpenAlex: W2009332633
Cited by: 302
References: 95
Citations by year: 2026: 18 · 2025: 27 · 2024: 34 · 2023: 35 · 2022: 22 · 2021: 46 · 2020: 32 · 2019: 23 · 2018: 28 · 2017: 17 · 2016: 11 · 2015: 4 · 2014: 4
FWCI: 1.03
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: other-oa
creativecommons.org/licenses/by-nc/3.0 (tdm)
Locations: Biomolecules & Therapeutics (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Funders: Japan Society for the Promotion of Science (23370057, 24590073)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords: very long chain fatty acids, fatty acid synthesis, fatty acid degradation, ichthyosis, macular degeneration, myopathy, demyelination, lipid mediators, sphingolipids, tissue distribution

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Metabolism of Very Long-Chain Fatty Acids: Genes and Pathophysiology

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