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

• Published in: Journal of lipid research 2020-04, Vol.61 (4), p.523-536
• Main Authors: Hama, Kotaro, Fujiwara, Yuko, Takashima, Shigeo, Hayashi, Yasuhiro, Yamashita, Atsushi, Shimozawa, Nobuyuki, Yokoyama, Kazuaki
• Format: Article
• Language: English
• Subjects: adenosine 5′-triphosphate; fatty acid; fatty acid/metabolism; hexacosenoyl (26:1)-coenzyme A; inherited metabolic disorder; lipidomics; lipids; Patient-Oriented and Epidemiological Research; peroxisomes; very long-chain fatty acid; X-linked adrenoleukodystrophy
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.P119000325

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.