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Cited by 16Metabolism and Genetic DisordersLipid metabolism and biosynthesisCholesterol and Lipid Metabolism

Hexacosenoyl-CoA is the most abundant very long-chain acyl-CoA in ATP binding cassette transporter D1-deficient cells

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Hama, Kotaro, Fujiwara, Yuko, Takashima, Shigeo, Hayashi, Yasuhiro, Yamashita, Atsushi, Shimozawa, Nobuyuki, Yokoyama, Kazuaki·2020·Journal of Lipid Research
DOI 10.1194/jlr.p119000325PMC PMC7112142
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Abstract

gene. The ABCD1 protein transports very long-chain FAs (VLCFAs) from the cytosol into the peroxisome where the VLCFAs are degraded through β-oxidation. ABCD1 dysfunction leads to VLCFA accumulation in individuals with X-ALD. FAs are activated by esterification to CoA before metabolic utilization. However, the intracellular pools and metabolic profiles of individual acyl-CoA esters have not been fully analyzed. In this study, we profiled the acyl-CoA species in fibroblasts from X-ALD patients and in ABCD1-deficient HeLa cells. We found that hexacosenoyl (26:1)-CoA, but not hexacosanoyl (26:0)-CoA, was the most abundantly concentrated among the VLCFA-CoA species in these cells. We also show that 26:1-CoA is mainly synthesized from oleoyl-CoA, and the metabolic turnover rate of 26:1-CoA was almost identical to that of oleoyl-CoA in both WT and ABCD1-deficient HeLa cells. The findings of our study provide precise quantitative and metabolic information of each acyl-CoA species in living cells. Our results suggest that VLCFA is endogenously synthesized as VLCFA-CoA through a FA elongation pathway and is then efficiently converted to other metabolites, such as phospholipids, in the absence of ABCD1.

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  • ALDP transports VLCFA across the peroxisomal membrane, preferentially as saturated and monounsaturated VLCFAcyl-CoA, notably C22:0-CoA, C24:0-CoA, C26:0-CoA, and C26:1-CoA.

    “ALDP transports VLCFA across the peroxisomal membrane [143], preferentially as saturated and monounsaturated VLCFAcyl-CoA, notably C22:0–CoA, C24:0–CoA, C26:0–CoA, and C26:1–CoA [143,144,145,146].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [145]

    The introductory passage (page unavailable) states that ABCD1 transports VLCFAs into peroxisomes. The Discussion and Results (pages unavailable) examine several VLCFA-CoA species, including 26:1-CoA, but do not establish that ALDP preferentially transports saturated and monounsaturated VLCFA-CoAs or identify the listed four as preferred transport substrates. (LLM, conf=0.84)

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Research works printed but not linked: 27

  1. [2]Kihara A. 2012 Very long-chain fatty acids: elongation, physiology and related disorders. J. Biochem. 152: 387– 395. 22984005
  2. [3]Moser H. W., Smith K. D., Watkins P., Powers J., and Moser A. B. 2002 X-linked adrenoleukodystrophy. In The Metabolic and Molecular Bases of Inherited Disease. 8th edition. McGraw-Hill, New York. 3257–3301.
  3. [4]Mahmood A., Raymond G. V., Dubey P., Peters C., and Moser H. W. 2007 Survival analysis of haematopoietic cell transplantation for childhood cerebral X-linked adrenoleukodystrophy: a comparison study. Lancet Neurol. 6: 687– 692. 17618834
  4. [5]Miller W. P., Rothman S. M., Nascene D., Kivisto T., DeFor T. E., Ziegler R. S., Eisengart J., Leiser K., Raymond G., Lund T. C., 2011 Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood. 118: 1971– 1978. 21586746
  5. [7]López-Erauskin J., Fourcade S., Galino J., Ruiz M., Schluter A., Naudi A., Jove M., Portero-Otin M., Pamplona R., Ferrer I., 2011 Antioxidants halt axonal degeneration in a mouse model of X-adrenoleukodystrophy. Ann. Neurol. 70: 84– 92. 21786300 PMC3229843
  6. [8]Hama K., Fujiwara Y., Morita M., Yamazaki F., Nakashima Y., Takei S., Takashima S., Setou M., Shimozawa N., Imanaka T., 2018 Profiling and imaging of phospholipids in brains of Abcd1-deficient mice. Lipids. 53: 85– 102. 29469952
  7. [10]Takashima S., Toyoshi K., Itoh T., Kajiwara N., Honda A., Ohba A., Takemoto S., Yoshida S., and Shimozawa N. 2017 Detection of unusual very-long-chain fatty acid and ether lipid derivatives in the fibroblasts and plasma of patients with peroxisomal diseases using liquid chromatography-mass spectrometry. Mol. Genet. Metab. 120: 255– 268. 28089346
  8. [11]Abe Y., Honsho M., Nakanishi H., Taguchi R., and Fujiki Y. 2014 Very-long-chain polyunsaturated fatty acids accumulate in phosphatidylcholine of fibroblasts from patients with Zellweger syndrome and acyl-CoA oxidase1 deficiency. Biochim. Biophys. Acta. 1841: 610– 619. 24418004
  9. [12]Herzog K., Pras-Raves M. L., Ferdinandusse S., Vervaart M. A. T., Luyf A. C. M., van Kampen A. H. C., Wanders R. J. A., Waterham H. R., and Vaz F. M. 2018 Functional characterisation of peroxisomal beta-oxidation disorders in fibroblasts using lipidomics. J. Inherit. Metab. Dis. 41: 479– 487. 28849344 PMC5959964
  10. [13]Lee D. K., Long N. P., Jung J., Kim T. J., Na E., Kang Y. P., Kwon S. W., and Jang J. 2019 Integrative lipidomic and transcriptomic analysis of X-linked adrenoleukodystrophy reveals distinct lipidome signatures between adrenomyeloneuropathy and childhood cerebral adrenoleukodystrophy. Biochem. Biophys. Res. Commun. 508: 563– 569. 30509496
  11. [14]Grevengoed T. J., Klett E. L., and Coleman R. A. 2014 Acyl-CoA metabolism and partitioning. Annu. Rev. Nutr. 34: 1– 30. 24819326 PMC5881898
  12. [15]Okuyama H., Lands W. E., Christie W. W., and Gunstone F. D. 1969 Selective transfer of cyclopropane acids by acyl coenzyme A: phospholipid acyltransferases. J. Biol. Chem. 244: 6514– 6519. 5354965
  13. [16]Minkler P. E., Kerner J., Ingalls S. T., and Hoppel C. L. 2008 Novel isolation procedure for short-, medium-, and long-chain acyl-coenzyme A esters from tissue. Anal. Biochem. 376: 275– 276. 18355435 PMC2444051
  14. [17]Hama K., Fujiwara Y., and Yokoyama K. 2018 Quantitative and qualitative method for sphingomyelin by LC-MS using two stable isotopically labeled sphingomyelin species. J. Vis. Exp. doi: 10.3791/57293. PMC6101123 29782002 · DOI
  15. [18]Hama K., Fujiwara Y., Tabata H., Takahashi H., and Yokoyama K. 2017 Comprehensive quantitation using two stable isotopically labeled species and direct detection of N-acyl moiety of sphingomyelin. Lipids. 52: 789– 799. 28770378 PMC5583271
  16. [19]Gu H., Liu G., Wang J., Aubry A. F., and Arnold M. E. 2014 Selecting the correct weighting factors for linear and quadratic calibration curves with least-squares regression algorithm in bioanalytical LC-MS/MS assays and impacts of using incorrect weighting factors on curve stability, data quality, and assay performance. Anal. Chem. 86: 8959– 8966. 25157966
  17. [21]Ran F. A., Hsu P. D., Wright J., Agarwala V., Scott D. A., and Zhang F. 2013 Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8: 2281– 2308. 24157548 PMC3969860
  18. [22]Haynes C. A. 2011 Analysis of mammalian fatty acyl-coenzyme A species by mass spectrometry and tandem mass spectrometry. Biochim. Biophys. Acta. 1811: 663– 668. 21679775
  19. [23]Magnes C., Sinner F. M., Regittnig W., and Pieber T. R. 2005 LC/MS/MS method for quantitative determination of long-chain fatty acyl-CoAs. Anal. Chem. 77: 2889– 2894. 15859607
  20. [24]Burla B., Arita M., Arita M., Bendt A. K., Cazenave-Gassiot A., Dennis E. A., Ekroos K., Han X., Ikeda K., Liebisch G., 2018 MS-based lipidomics of human blood plasma: a community-initiated position paper to develop accepted guidelines. J. Lipid Res. 59: 2001– 2017. 30115755 PMC6168311
  21. [25]Yamashita A., Hayashi Y., Nemoto-Sasaki Y., Ito M., Oka S., Tanikawa T., Waku K., and Sugiura T. 2014 Acyltransferases and transacylases that determine the fatty acid composition of glycerolipids and the metabolism of bioactive lipid mediators in mammalian cells and model organisms. Prog. Lipid Res. 53: 18– 81. 24125941
  22. [27]Sun D., Cree M. G., and Wolfe R. R. 2006 Quantification of the concentration and 13C tracer enrichment of long-chain fatty acyl-coenzyme A in muscle by liquid chromatography/mass spectrometry. Anal. Biochem. 349: 87– 95. 16307720
  23. [28]Zhang G. F., Kombu R. S., Kasumov T., Han Y., Sadhukhan S., Zhang J., Sayre L. M., Ray D., Gibson K. M., Anderson V. A., 2009 Catabolism of 4-hydroxyacids and 4-hydroxynonenal via 4-hydroxy-4-phosphoacyl-CoAs. J. Biol. Chem. 284: 33521– 33534. 19759021 PMC2785196
  24. [29]Yamashita A., Sugiura T., and Waku K. 1997 Acyltransferases and transacylases involved in fatty acid remodeling of phospholipids and metabolism of bioactive lipids in mammalian cells. J. Biochem. 122: 1– 16. 9276665
  25. [30]Pewzner-Jung Y., Ben-Dor S., and Futerman A. H. 2006 When do Lasses (longevity assurance genes) become CerS (ceramide synthases)?: Insights into the regulation of ceramide synthesis. J. Biol. Chem. 281: 25001– 25005. 16793762
  26. [31]Valianpour F., Selhorst J. J., van Lint L. E., van Gennip A. H., Wanders R. J., and Kemp S. 2003 Analysis of very long-chain fatty acids using electrospray ionization mass spectrometry. Mol. Genet. Metab. 79: 189– 196. 12855224
  27. [32]Hama K., Nagai T., Nishizawa C., Ikeda K., Morita M., Satoh N., Nakanishi H., Imanaka T., Shimozawa N., Taguchi R., 2013 Molecular species of phospholipids with very long chain fatty acids in skin fibroblasts of Zellweger syndrome. Lipids. 48: 1253– 1267. 24122089

Cited by

Sorted by citations

Authors
Hama, K., Fujiwara, Y., Takashima, S., Hayashi, Y., Yamashita, A., Shimozawa, N., & Yokoyama, K.
Affiliations
  • Teikyo University (JP)
  • Gifu University (JP)
Corresponding author
Hama, Kotaro
ORCID
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2020-04
Volume
61
Issue
4
Pages
523-536
ISSN
0022-2275 (ISSN-L)
DOI
10.1194/jlr.p119000325
PMC
PMC7112142
OpenAlex
W3008249294
Cited by
16
References
5
Citations by year
2025: 8 · 2022: 5 · 2021: 2 · 2020: 1
FWCI
1.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Lipid Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
Funders
  • Ministry of Education, Culture, Sports, Science, and Technology (15K01691, 19K11777, 15K08625, 17K10062)
  • Promotion and Mutual Aid Corporation for Private Schools of Japan
  • Ichiro Kanehara Foundation
  • Kawano Masanori Memorial Public Interest Incorporated Foundation
  • Fugaku Trust for Medical Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
ABCD1, X-linked adrenoleukodystrophy, very long chain fatty acids, oleoyl-CoA, fatty acid elongation, fatty acid beta-oxidation, phospholipid synthesis
MeSH terms
ATP Binding Cassette Transporter, Subfamily D, Member 1, Acyl Coenzyme A, Fibroblasts, HeLa Cells, Humans, Gene Knockout Techniques

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