The development of diagnostic marker and therapeutic target for inherited metabolic disorders

2019 Fiscal Year Final Research Report

• Project/Area Number: 15K01691
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Teikyo University
• Principal Investigator: Hama Kotaro 帝京大学, 薬学部, 准教授 (20534481)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Keywords: 副腎白質ジストロフィー

Outline of Final Research Achievements

VLCFA are transported by ABCD1 into the peroxisome where they are degraded by β-oxidation. ABCD1 is the causative gene of X-ALD. Fatty acyl-coenzyme A (acyl-CoA) is an active form and serves as metabolic intermediates of fatty acids. Acyl-CoA is composed of both a hydrophobic fatty acyl moiety and a hydrophobic CoA joined with a thioester linkage. The intracellular pool of each acyl-CoA ester has not yet 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 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 wild-type and ABCD1-deficient HeLa cells. The findings of our study provide quantitative and metabolic information of each acyl-CoA species in living cells.

Free Research Field

脂質生物学

Academic Significance and Societal Importance of the Research Achievements

副腎白質ジストロフィーの患者間では、その発症時期、症状の程度に大きな違いが存在し、治療を難しくしている。副腎白質ジストロフィーのすべての亜型では極長鎖脂肪酸が上昇しているものの、その亜型特異的な特徴は見出されていない。現在臨床上用いられている極長鎖脂肪酸の測定方法は、脂肪酸の総量を測定するものであり、生体内の存在様式は反映されない。申請者は今回、活性化状態として存在する脂肪酸、および、生体内に存在する極長鎖脂肪酸含有複合脂質を定量した。極長鎖脂肪酸含有脂質の産生代謝および輸送過程を制御することができれば、新しい創薬対象が見出される可能性があり、本研究はその基礎的な情報として重要である。