FAMINは,ピューリン核酸循環を可能にする多機能ピューリン酵素である
M Zaeem Cader1, Rodrigo Pereira de Almeida Rodrigues1, James A West2
1Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Cell
|January 25, 2020
まとめ
FAMIN酵素はアデノシンを分解し,以前は真核生物では知られていませんでした. この発見は,FAMINを明らかにします.
科学分野:
- 生物化学
- 分子生物学
- 遺伝学
背景:
- FAMINの変異は早期発症の関節炎と炎症性腸疾患に関連しています.
- FAMINの一般的な遺伝的変異は,クローン病と麻痺の感受性を高めます.
研究 の 目的:
- 偏見のないスクリーニングアプローチを用いて孤児タンパク質FAMINの酵素活性を特定する.
- ユーカリオット細胞,特にマクロファージにおけるFAMINの代謝作用を解明する.
主な方法:
- 酵素活性を検出するための偏らない液体染色体質スペクトロメトリースクリーンの開発.
- FAMINによるアデノシン分裂を特徴付けるための生化学的測定.
- FAMINを含むマクロファージにおけるピューリンヌクレオチドサイクル (PNC) の分析.
主要な成果:
- FAMINはアデノシンをアデニンとリボス-1-リン酸に分解し,以前はユーカリ生物で特徴づけられていなかった.
- FAMINおよびそのプロカリオティック・オートロゴはアデノシン・デアミナーゼ,ピューリン・ヌクレオシド・フォスフォリラーゼ,およびS-メチル-5'-チオアデノシン・フォスフォリラーゼの活性を示す.
- FAMINは,脂肪酸の酸化とATP-シトラートライアースの活動をリンクして,ミトコンドリアの呼吸と糖分分解を同期させ,マクロファージのピューリンヌクレオチドサイクルを促進します.
結論:
- FAMINは,真核生物の purin 代謝に不可欠な新しい酵素活性を持っています.
- FAMINによって調節されるマクロファージのピューリン核酸循環は,細胞のエネルギー代謝のバランスをとる上で重要な役割を果たします.
- この発見は,FAMINに関連した炎症性疾患を理解し,潜在的に治療するための新しい道を開きます.
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