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Review
. 2014 Feb;22(2):83-92.
doi: 10.4062/biomolther.2014.017.

Metabolism of very long-chain Fatty acids: genes and pathophysiology

Takayuki Sassa  1 , Akio Kihara  1
Affiliations
Review

Metabolism of very long-chain Fatty acids: genes and pathophysiology

Takayuki Sassa et al. Biomol Ther (Seoul). 2014 Feb.

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.

Keywords: Ceramide; ELOVL; Glycerophospholipids; Ichthyosis; Leukodystrophy; Sphingolipids.

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Figures

Fig. 1.
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.
Fig. 2.
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.
Fig. 3.
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.
See this image and copyright information in PMC

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