小柯机器人

利用极性氧代谢组揭示4-羟基扁桃酸CoQ10合成途径，这一成果由纽约大学朗格尼医学中心Pacold, Michael E.研究小组经过不懈努力而取得。该研究成果在线发表在2021年9月1日的《自然》上。

研究人员用¹⁸O₂标记了不同组织来源的细胞系，通过既定情况下不同生理 O₂ 压力下 ¹⁸O₂标记的极性代谢物来识别极性氧代谢组。¹⁸O₂标记最高的产物是4-羟基扁桃酸 (4-HMA)。研究人员证明4-HMA是由类羟苯基丙酮酸双加氧酶(HPDL)产生，HPDL是人细胞中未知功能的一种蛋白质。研究人员发现4-HMA是人体细胞中辅酶 Q10 (CoQ10)头部基团生物合成的中间体。HPDL与CoQ10生物合成之间的关联为最近发现的与HPDL缺陷相关神经系统疾病和HPDL过表达癌症的潜在发病机制提供了见解。

据了解，氧气对于人类生命必不可少因为其对于多种代谢过程至关重要。可以通过用18O2或其他同位素标记气体处理细胞，并通过系统地识别包含标记原子生物分子来区分生物过程。

附：英文原文

Title: The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway

Author: Banh, Robert S., Kim, Esther S., Spillier, Quentin, Biancur, Douglas E., Yamamoto, Keisuke, Sohn, Albert S. W., Shi, Guangbin, Jones, Drew R., Kimmelman, Alec C., Pacold, Michael E.

Issue&Volume: 2021-09-01

Abstract: Oxygen is critical for a multitude of metabolic processes that are essential for human life. Biological processes can be identified by treating cells with 18O2 or other isotopically labelled gases and systematically identifying biomolecules incorporating labeled atoms. Here we labelled cell lines of distinct tissue origins with 18O2 to identify the polar oxy-metabolome, defined as polar metabolites labelled with 18O under different physiological O2 tensions. The most highly 18O-labelled feature was 4-hydroxymandelate (4-HMA). We demonstrate that 4-HMA is produced by hydroxyphenylpyruvate dioxygenase-like (HPDL), a protein of previously unknown function in human cells. We identify 4-HMA as an intermediate involved in the biosynthesis of the coenzyme Q10 (CoQ10) headgroup in human cells. The connection of HPDL to CoQ10 biosynthesis provides crucial insights into the mechanisms underlying recently described neurological diseases related to HPDL deficiencies1,2,3,4 and cancers with HPDL overexpression5.

DOI: 10.1038/s41586-021-03865-w

Source: https://www.nature.com/articles/s41586-021-03865-w

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html