Department of Medicinal Chemistry, Science for Life Laboratory, Uppsala University, Box 574, SE-75123 Uppsala, Sweden.
Analyst. 2020 Jun 7;145(11):3822-3831. doi: 10.1039/d0an00150c. Epub 2020 May 12.
Metabolites with ketone or aldehyde functionalities comprise a large proportion of the human metabolome, most notably in the form of sugars. However, these reactive molecules are also generated through oxidative stress or gut microbiota metabolism and have been linked to disease development. The discovery and structural validation of this class of metabolites over the large concentration range found in human samples is crucial to identify their links to pathogenesis. Herein, we have utilized an advanced chemoselective probe methodology alongside bioinformatic analysis to identify carbonyl-metabolites in urine and fecal samples. In total, 99 metabolites were identified in urine samples and the chemical structure for 40 metabolites were unambiguously validated using a co-injection procedure. We also describe the preparation of a metabolite-conjugate library of 94 compounds utilized to efficiently validate these ketones and aldehydes. This method was used to validate 33 metabolites in a pooled fecal sample extract to demonstrate the potential for rapid and efficient metabolite detection over a wide metabolite concentration range. This analysis revealed the presence of six metabolites that have not previously been detected in either sample type. The constructed library can be utilized for straightforward, large-scale, and expeditious analysis of carbonyls in any sample type.
含酮或醛官能团的代谢物构成了人类代谢组的很大一部分，其中最显著的形式是糖。然而，这些反应性分子也通过氧化应激或肠道微生物群代谢产生，并与疾病的发展有关。在人类样本中发现和结构验证这一类代谢物对于确定它们与发病机制的联系至关重要。在这里，我们结合生物信息学分析，利用先进的化学选择性探针方法来鉴定尿液和粪便样本中的羰基代谢物。总共在尿液样本中鉴定出 99 种代谢物，通过共注射程序明确验证了 40 种代谢物的化学结构。我们还描述了 94 种化合物的代谢物缀合物文库的制备，用于有效地验证这些酮和醛。该方法用于验证混合粪便样本提取物中的 33 种代谢物，以证明在广泛的代谢物浓度范围内快速高效地检测代谢物的潜力。该分析揭示了六种以前在这两种样本类型中都没有检测到的代谢物的存在。所构建的文库可用于任何样本类型中羰基的简单、大规模和快速分析。
