Hexacosenoyl-CoA is the most abundant very long-chain acyl-CoA in ATP binding cassette transporter D1-deficient cells
| العنوان: | Hexacosenoyl-CoA is the most abundant very long-chain acyl-CoA in ATP binding cassette transporter D1-deficient cells |
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| المؤلفون: | Nobuyuki Shimozawa, Atsushi Yamashita, Kazuaki Yokoyama, Yuko Fujiwara, Kotaro Hama, Yasuhiro Hayashi, Shigeo Takashima |
| المصدر: | Journal of Lipid Research Journal of Lipid Research, Vol 61, Iss 4, Pp 523-536 (2020) |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Very long chain fatty acid, fatty acid/metabolism, ATP-binding cassette transporter, QD415-436, very long-chain fatty acid, 030204 cardiovascular system & hematology, ATP Binding Cassette Transporter, Subfamily D, Member 1, Biochemistry, lipids, Gene Knockout Techniques, 03 medical and health sciences, chemistry.chemical_compound, Acyl-CoA, 0302 clinical medicine, Endocrinology, medicine, Humans, X-linked adrenoleukodystrophy, adenosine 5′-triphosphate, chemistry.chemical_classification, Fatty acid metabolism, hexacosenoyl (26:1)-coenzyme A, peroxisomes, Fatty acid, inherited metabolic disorder, Cell Biology, Fibroblasts, Peroxisome, medicine.disease, Cytosol, 030104 developmental biology, chemistry, lipidomics, Adrenoleukodystrophy, fatty acid, Acyl Coenzyme A, Patient-Oriented and Epidemiological Research, HeLa Cells |
| الوصف: | X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder caused by deleterious mutations in the ABCD1 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. |
| تدمد: | 0022-2275 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d3668aee037a1139dda8a310a86c67b3Test https://doi.org/10.1194/jlr.p119000325Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d3668aee037a1139dda8a310a86c67b3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00222275 |
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