圣犹大儿童医院的研究人员发现当细胞缺乏辅酶A(CoA)时的动态基因和生物化学变化，辅酶A在代谢中扮演重要的角色。
代谢是维护细胞健康之所有生物化学反应的总和，包括分解及合成各种分子，以制造能量和满足细胞修补及正常运作的需要。辅酶A是生物体内代谢反应中乙酰化酶的辅酶，它的前体是维生素(B3)泛酸。CoA 在细胞的代谢中扮演的关键角色。
这项研究结果发表于3月号的Chemistry and Biology中。圣犹大的研究人员利用小鼠模型研究细胞缺乏CoA时的反应，他们利用hopantenate (HoPan)抑制小鼠的CoA制造。HoPan 是一种会干扰泛酸盐激酶(PanK)的化学物质，而PanK会引起CoA生产的第一步。
当CoA停止制造后，细胞会迅速地回收CoA，使它可以集中于唯一的任务：从粒线体中的营养素萃取维持生命的能量。这项研究结果提供迄今最详细的概观，让科学家们了解细胞面临紧迫时，引起复杂的代谢变化。
部分英文原文：
Chemistry and Biology, Vol 14, 291-302, 23 March 2007
Article
Chemical Knockout of Pantothenate Kinase Reveals the Metabolic and Genetic Program Responsible for Hepatic Coenzyme A Homeostasis
Yong-Mei Zhang,1 Shigeru Chohnan,1,4 Kristopher G. Virga,2 Robert D. Stevens,3 Olga R. Ilkayeva,3 Brett R. Wenner,3 James R. Bain,3 Christopher B. Newgard,3 Richard E. Lee,2 Charles O. Rock,1 and Suzanne Jackowski1,
1 Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
2 Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA
3 Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27704, USA
Corresponding author
Suzanne Jackowski
suzanne.jackowski@stjude.org
Summary
Coenzyme A (CoA) is the major acyl group carrier in intermediary metabolism. Hopantenate (HoPan), a competitive inhibitor of the pantothenate kinases, was used to chemically antagonize CoA biosynthesis. HoPan dramatically reduced liver CoA and mice developed severe hypoglycemia. Insulin was reduced, glucagon and corticosterone were elevated, and fasting accelerated hypoglycemia. Metabolic profiling revealed a large increase in acylcarnitines, illustrating the role of carnitine in buffering acyl groups to maintain the nonesterified CoASH level. HoPan triggered significant changes in hepatic gene expression that substantially increased the thioesterases, which liberate CoASH from acyl-CoA, and increased pyruvate dehydrogenase kinase 1, which prevents the conversion of CoASH to acetyl-CoA. These results identify the metabolic rearrangements that maintain the CoASH pool which is critical to mitochondrial functions, including gluconeogenesis, fatty acid oxidation, and the tricarboxylic acid and urea cycles.
Molecular Cell：研究发现一种代谢酶控制着癌细胞-生物谷生物频道
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