論文 - 詳細
| RRC ID | 58776 |
|---|---|
| 著者 | Hama K, Fujiwara Y, Takashima S, Hayashi Y, Yamashita A, Shimozawa N, Yokoyama K. |
| タイトル | Hexacosenoyl-CoA is the most abundant very long-chain acyl-CoA in ATP binding cassette transporter D1-deficient cells. |
| ジャーナル | J Lipid Res |
| Abstract |
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. |
| 巻・号 | 61(4) |
| ページ | 523-536 |
| 公開日 | 2020-4-1 |
| DOI | 10.1194/jlr.P119000325 |
| PII | S0022-2275(20)43502-3 |
| PMID | 32075856 |
| PMC | PMC7112142 |
| MeSH | ATP Binding Cassette Transporter, Subfamily D, Member 1 / deficiency* ATP Binding Cassette Transporter, Subfamily D, Member 1 / genetics Acyl Coenzyme A / metabolism* Fibroblasts / metabolism Gene Knockout Techniques HeLa Cells Humans |
| IF | 4.483 |
| 引用数 | 0 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa |