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辅酶A生物合成:调控、功能和疾病机制

Coenzyme A biosynthesis: mechanisms of regulation, function and disease

Nature 等信源发布 2024-06-13 23:53

可切换为仅中文


AbstractThe tricarboxylic acid cycle, nutrient oxidation, histone acetylation and synthesis of lipids, glycans and haem all require the cofactor coenzyme A (CoA). Although the sources and regulation of the acyl groups carried by CoA for these processes are heavily studied, a key underlying question is less often considered: how is production of CoA itself controlled? Here, we discuss the many cellular roles of CoA and the regulatory mechanisms that govern its biosynthesis from cysteine, ATP and the essential nutrient pantothenate (vitamin B5), or from salvaged precursors in mammals.

摘要三羧酸循环,营养氧化,组蛋白乙酰化以及脂质,聚糖和血红素的合成都需要辅因子辅酶A(CoA)。尽管对CoA在这些过程中携带的酰基的来源和调节进行了大量研究,但很少考虑一个关键的潜在问题:如何控制CoA本身的生产?在这里,我们讨论了辅酶A的许多细胞作用以及控制其从半胱氨酸,ATP和必需营养素泛酸盐(维生素B5)或哺乳动物中回收的前体生物合成的调节机制。

Metabolite feedback and signalling mechanisms involving acetyl-CoA, other acyl-CoAs, acyl-carnitines, MYC, p53, PPARα, PINK1 and insulin- and growth factor-stimulated PI3K–AKT signalling regulate the vitamin B5 transporter SLC5A6/SMVT and CoA biosynthesis enzymes PANK1, PANK2, PANK3, PANK4 and COASY.

涉及乙酰辅酶A,其他酰基辅酶A,酰基肉碱,MYC,p53,PPARα,PINK1以及胰岛素和生长因子刺激的PI3K-AKT信号传导的代谢物反馈和信号传导机制调节维生素B5转运蛋白SLC5A6/SMVT和CoA生物合成酶PANK1,PANK2,PANK3,PANK4和COASY。

We also discuss methods for measuring CoA-related metabolites, compounds that target CoA biosynthesis and diseases caused by mutations in pathway enzymes including types of cataracts, cardiomyopathy and neurodegeneration (PKAN and COPAN)..

我们还讨论了测量CoA相关代谢物,靶向CoA生物合成的化合物以及由途径酶突变引起的疾病(包括白内障,心肌病和神经退行性疾病(PKAN和COPAN))的方法。。

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Fig. 1: Functions of CoA.Fig. 2: The de novo CoA biosynthesis pathway.Fig. 3: CoA degradation and salvage pathways.Fig. 4: Metabolite-based regulation of CoA biosynthesis.Fig. 5: Signalling-mediated regulation of CoA biosynthesis.

图1:CoA的功能。图2:从头CoA生物合成途径。图3:CoA降解和挽救途径。图4:CoA生物合成的基于代谢物的调节。图5:信号传导介导的CoA生物合成调节。

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Cole in support of S.E.D.-C.). We thank K.E. Wellen and N.W. Snyder for the helpful discussion of their data, our peer reviewers for their expert feedback, and our primary editor for his guidance and patience. We express our appreciation and respect for Charles O. Rock, a pioneer in the fields of CoA and lipid metabolism who passed away in 2023.Author informationAuthors and AffiliationsDepartment of Pathology, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USASamuel A.

科尔支持S.E.D.-C.)。我们感谢K.E.Wellen和N.W.Snyder对他们的数据进行了有益的讨论,感谢我们的同行评论者的专家反馈,感谢我们的主要编辑的指导和耐心。我们对Charles O.Rock表示赞赏和敬意,他是辅酶a和脂质代谢领域的先驱,于2023年去世。作者信息作者和附属机构美国马萨诸塞州波士顿哈佛医学院贝斯以色列女执事医学中心病理学系Samuel a。

Barritt & Christian C. DibbleDepartment of Medicine, Department of Biological Chemistry and Molecular Pharmacology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USASarah E. DuBois-CoyneAuthorsSamuel A. BarrittView author publicationsYou can also search for this author in.

Barritt&Christian C.DibbleDepartment of Medicine,Department of Biological Chemistry and Molecular Pharmacology,Brigham and Women's Hospital,Harvard Medical School,Boston,MA,USA Sarah E.DuBois CoyneAuthorsSamuel A.BarrittView author Publications您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsConceptualization: S.A.B. and C.C.D. Writing, figure construction and editing: S.A.B., S.E.D.-C. and C.C.D.Corresponding authorCorrespondence to

PubMed谷歌学术贡献概念:S.A.B.和C.C.D.写作,图形构建和编辑:S.A.B.,S.E.D.-C.和C.C.D.对应作者

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Nature Metabolism thanks Charles Rock and Ivan Gout for their contribution to the peer review of this work. Primary Handling Editor: Alfredo Gimenez-Cassina, in collaboration with the Nature Metabolism team.

《自然代谢》感谢查尔斯·洛克(CharlesRock)和伊凡·痛风(IvanGout)为这项工作的同行评审所做的贡献。主要处理编辑:阿尔弗雷多·吉梅内斯·卡西纳(AlfredoGimenezCassina),与《自然代谢》团队合作。

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& Dibble, C.C. Coenzyme A biosynthesis: mechanisms of regulation, function and disease..

&Dibble,C.C.辅酶A生物合成:调节,功能和疾病的机制。。

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