| 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
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| 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
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| 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
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa |
