Production and metabolism of very long-chain fatty acids and pathology due to their abnormal metabolism

2017 Fiscal Year Final Research Report

• Project/Area Number: 26251010
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Hokkaido University
• Principal Investigator: KIHARA Akio 北海道大学, 薬学研究院, 教授 (50333620)
• Co-Investigator(Renkei-kenkyūsha): SASSA Takayuki 北海道大学, 大学院薬学研究院, 准教授 (20342793) ; OHNO Yusuke 北海道大学, 大学院薬学研究院, 助教 (50611498)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 脂質 / 代謝 / 脂肪酸

Outline of Final Research Achievements

In the fatty acid elongation cycle, which produces very long-chain fatty acids, four reactions are catalyzed by ELOVL1-7, KAR, HACD1-4, and TER. In the present study, we elucidated the molecular mechanism of myopathy and the differences in the substrate specificity of HACD1-4, using knockout mice or knockout cells of HACD genes. Analyses using ELOVL mutant mice and biochemical assays revealed the substrate specificity of ELOVLs and the mechanism of activity regulation of ELOVL6 by KAR. We identified fatty acid omega-hydroxylase CYP4F22 as the gene involved in the production of the very long-chain lipid acylceramide, which is important for skin barrier formation, and elucidated the molecular mechanism of ichthyosis. We revealed a new function of TER other than fatty acid elongation.

Free Research Field

脂質生化学