<br>肠道细菌衍生代谢物苯乙酰谷氨酰胺在健康和疾病中的作用,ACS Omega

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肠道细菌衍生代谢物苯乙酰谷氨酰胺在健康和疾病中的作用
ACS Omega ( IF 3.7 ) Pub Date : 2024-01-08 , DOI: 10.1021/acsomega.3c08184
Naveen Kumar Krishnamoorthy _{1,

2} , Manjunath Kalyan _{1,

2} , Tousif Ahmed Hediyal _{1,

2} , Nikhilesh Anand ₃ , Pavan Heggadadevanakote Kendaganna ₂ , Gurudutt Pendyala _{4,

5,

6,

7} , Sowmya V Yelamanchili _{4,

5,

7} , Jian Yang ₈ , Saravana Babu Chidambaram _{1,

2} , Meena Kishore Sakharkar ₈ , Arehally M Mahalakshmi _{1,

2}

Affiliation

在过去的几十年里，已经确定肠道微生物群衍生的代谢物会破坏肠道功能，从而导致一系列疾病。值得注意的是，苯乙酰谷氨酰胺（PAGln）是一种细菌衍生的代谢产物，由于其在心脑血管疾病的发生和发展中的作用，最近受到关注。这种元生物代谢物 PAGln 是其前体苯乙酸（PAA）从鸡蛋、肉类、乳制品等一系列饮食来源中氨基酸乙酰化的副产品。苯丙氨酸的微生物群依赖性代谢产生 PAA，PAA 是由多种微生物催化途径催化的重要中间体。PAA 与肝脏和肾脏中的谷氨酰胺和甘氨酸结合，主要在人类中形成苯乙酰谷氨酰胺，在啮齿动物中形成苯乙酰甘氨酸。PAGln 与血栓形成有关，因为它增强通过 GPCRs 受体 α2A、α2B 和 β2 ADRs 介导的血小板活化，从而加重病理状况。临床证据表明，PAGln 水平升高与心血管、脑血管和神经系统疾病的病理有关。本文进一步巩固了 PAGln 的微生物/生化合成，并讨论了其在上述病理理学中的作用。

"点击查看英文标题和摘要"

Role of the Gut Bacteria-Derived Metabolite Phenylacetylglutamine in Health and Diseases

Over the past few decades, it has been well established that gut microbiota-derived metabolites can disrupt gut function, thus resulting in an array of diseases. Notably, phenylacetylglutamine (PAGln), a bacterial derived metabolite, has recently gained attention due to its role in the initiation and progression of cardiovascular and cerebrovascular diseases. This meta-organismal metabolite PAGln is a byproduct of amino acid acetylation of its precursor phenylacetic acid (PAA) from a range of dietary sources like egg, meat, dairy products, etc. The microbiota-dependent metabolism of phenylalanine produces PAA, which is a crucial intermediate that is catalyzed by diverse microbial catalytic pathways. PAA conjugates with glutamine and glycine in the liver and kidney to predominantly form phenylacetylglutamine in humans and phenylacetylglycine in rodents. PAGln is associated with thrombosis as it enhances platelet activation mediated through the GPCRs receptors α2A, α2B, and β2 ADRs, thereby aggravating the pathological conditions. Clinical evidence suggests that elevated levels of PAGln are associated with pathology of cardiovascular, cerebrovascular, and neurological diseases. This Review further consolidates the microbial/biochemical synthesis of PAGln and discusses its role in the above pathophysiologies.

更新日期：2024-01-08

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