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磷脂酰基转移酶:酶在代谢和癌症疾病中的特性及作用

Phospholipid Acyltransferases: Characterization and Involvement of the Enzymes in Metabolic and Cancer Diseases.

作者信息

Korbecki Jan, Bosiacki Mateusz, Pilarczyk Maciej, Gąssowska-Dobrowolska Magdalena, Jarmużek Paweł, Szućko-Kociuba Izabela, Kulik-Sajewicz Justyna, Chlubek Dariusz, Baranowska-Bosiacka Irena

机构信息

Department of Anatomy and Histology, Collegium Medicum, University of Zielona Góra, Zyty 28, 65-046 Zielona Góra, Poland.

Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.

出版信息

Cancers (Basel). 2024 May 31;16(11):2115. doi: 10.3390/cancers16112115.

Abstract

This review delves into the enzymatic processes governing the initial stages of glycerophospholipid (phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine) and triacylglycerol synthesis. The key enzymes under scrutiny include GPAT and AGPAT. Additionally, as most AGPATs exhibit LPLAT activity, enzymes participating in the Lands cycle with similar functions are also covered. The review begins by discussing the properties of these enzymes, emphasizing their specificity in enzymatic reactions, notably the incorporation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid and docosahexaenoic acid (DHA) into phospholipids. The paper sheds light on the intricate involvement of these enzymes in various diseases, including obesity, insulin resistance, and cancer. To underscore the relevance of these enzymes in cancer processes, a bioinformatics analysis was conducted. The expression levels of the described enzymes were correlated with the overall survival of patients across 33 different types of cancer using the GEPIA portal. This review further explores the potential therapeutic implications of inhibiting these enzymes in the treatment of metabolic diseases and cancer. By elucidating the intricate enzymatic pathways involved in lipid synthesis and their impact on various pathological conditions, this paper contributes to a comprehensive understanding of these processes and their potential as therapeutic targets.

摘要

本综述深入探讨了甘油磷脂(磷脂酰胆碱、磷脂酰乙醇胺和磷脂酰丝氨酸)和三酰甘油合成初始阶段的酶促过程。受到审查的关键酶包括甘油磷酸酰基转移酶(GPAT)和酰基甘油磷酸酰基转移酶(AGPAT)。此外,由于大多数AGPAT具有溶血磷脂酸酰基转移酶(LPLAT)活性,参与兰兹循环且功能相似的酶也在讨论范围内。综述首先讨论了这些酶的特性,强调了它们在酶促反应中的特异性,特别是将花生四烯酸和二十二碳六烯酸(DHA)等多不饱和脂肪酸(PUFA)掺入磷脂中的过程。本文揭示了这些酶在肥胖、胰岛素抵抗和癌症等各种疾病中的复杂作用。为了强调这些酶在癌症过程中的相关性,进行了一项生物信息学分析。使用GEPIA门户将所述酶的表达水平与33种不同类型癌症患者的总生存率相关联。本综述进一步探讨了抑制这些酶在代谢疾病和癌症治疗中的潜在治疗意义。通过阐明参与脂质合成的复杂酶促途径及其对各种病理状况的影响,本文有助于全面了解这些过程及其作为治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1279/11171337/dced45e02787/cancers-16-02115-g001.jpg

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