Go Young-Mi, Walker Douglas I, Soltow Quinlyn A, Uppal Karan, Wachtman Lynn M, Strobel Fredrick H, Pennell Kurt, Promislow Daniel E L, Jones Dean P
Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University, 205 Whitehead Research Center, Atlanta, GA, 30322, USA.
Amino Acids. 2015 Mar;47(3):589-601. doi: 10.1007/s00726-014-1893-x. Epub 2014 Dec 21.
Little systematic knowledge exists concerning the impacts of cumulative lifelong exposure, termed the exposome, on requirements for nutrients. Phenylalanine (Phe) is an essential dietary amino acid with an aromatic ring structure similar to endogenous metabolites, dietary compounds and environmental agents. Excess plasma Phe in genetic disease or nutritional deficiency of Phe has adverse health consequences. In principle, structurally similar chemicals interfering with Phe utilization could alter Phe requirement at an individual level. As a strategy to identify components of the exposome that could interfere with Phe utilization, we tested for metabolites correlating with Phe concentration in plasma of a non-human primate species, common marmosets (Callithrix jacchus). The results of tests for more than 5,000 chemical features detected by high-resolution metabolomics showed 17 positive correlations with Phe metabolites and other amino acids. Positive and negative correlations were also observed for 33 other chemicals, which included matches to endogenous metabolites and dietary, microbial and environmental chemicals in database searches. Chemical similarity analysis showed many of the matches had high structural similarity to Phe. Together, the results show that chemicals in marmoset plasma could impact Phe utilization. Such chemicals could contribute to early lifecycle developmental disorders when neurological development is vulnerable to Phe levels.
关于累积终生暴露（即暴露组）对营养需求的影响，目前几乎没有系统的知识。苯丙氨酸（Phe）是一种必需的膳食氨基酸，其芳香环结构与内源性代谢物、膳食化合物和环境因子相似。在苯丙酮尿症等遗传疾病或苯丙氨酸营养缺乏症中，血浆苯丙氨酸过量会对健康产生不利影响。原则上，结构相似的化学物质干扰苯丙氨酸的利用可能会在个体水平上改变苯丙氨酸的需求量。作为一种识别可能干扰苯丙氨酸利用的暴露组成分的策略，我们测试了与一种非人类灵长类动物——普通狨猴（Callithrix jacchus）血浆中苯丙氨酸浓度相关的代谢物。通过高分辨率代谢组学检测到的5000多种化学特征的测试结果显示，有17种与苯丙氨酸代谢物和其他氨基酸呈正相关。还观察到另外33种化学物质存在正相关和负相关，在数据库搜索中，这些化学物质包括与内源性代谢物、膳食、微生物和环境化学物质相匹配的物质。化学相似性分析表明，许多匹配物质与苯丙氨酸具有高度的结构相似性。这些结果共同表明，狨猴血浆中的化学物质可能会影响苯丙氨酸的利用。当神经发育易受苯丙氨酸水平影响时，这些化学物质可能会导致生命周期早期发育障碍。
