多酶催化合成烟酰胺单核苷酸任务书

 2021-10-23 20:17:00

1. 毕业设计(论文)的内容和要求

一、论文内容: 烟酰胺单核苷酸是烟酰胺磷酸核糖转移酶(Nicotinamide phosphate ribose transferase,Nampt)反应的产物,是NAD 的关键前体之一。

在哺乳动物体内,烟酰胺单核苷酸由烟酰胺(Nicotinamide,Nam)在Nampt的催化下生成,随后烟酰胺单核苷酸在烟酰胺单核苷酸腺苷转移酶(Nicotinamide mononucleotide adenosine transferase)的催化下生成NAD 。

细胞外烟酰胺单核苷酸需要去磷酸转化为烟酰胺核苷(Nicotinamide riboside,NR)才能进入肝细胞内部,进入胞内后,NR在烟酰胺核苷激酶1(Nicotinamide riboside kinase,NRK1)的作用下磷酸化生成烟酰胺单核苷酸,随后烟酰胺单核苷酸和ATP结合生成NAD 。

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2. 参考文献

[1] Karson S. Putta and Paul J. Hergenrothera, An enzymatic assay for poly(ADP-ribose) polymerase-1 (PARP-1) via the chemical quantitation of NAD : application to the high-throughput screening of small molecules as potential inhibitors. Elsevier, 2003. 9(3): p. 1646-1652.[2] Laura Formentini, Flavio Moroni, Alberto Chiarugi, Detection and pharmacological modulation of nicotinamide mononucleotide in vitro and in vivo. Elsevier, 2009.2(19): 16121620.[3] Hazel B. Leung, Kalla L. Kvalnes-Krick, et al, Structure and Regulation of the AMP Nucleosidase Gene (amn) from Escherichia coli. Biochemistry, 1989,6(26): 8726-8733 .[4] Kathryn F. Mills, Shohei Yoshida, et al, Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. CellPress, 2012.12(23): 795-806.[5] Thomas Penfound and John W. Foster, NAD-Dependent DNA-Binding Activity of the Bifunctional NadR Regulator of Salmonella typhimurium. Journal Of Bacteriology,JAN.1999: p. 648-655.[6] Pei Wang and Chao-Yu Miao, NAMPT as a Therapeutic Target against Stroke.Trends in Pharmacological Sciences, December 2015, Vol. 36, No. 12 : 31146.[7] Ruo-Yu Zhang, Ye Qin, et al, A flfluorometric assay for high-throughput screening targeting nicotinamide phosphoribosyltransferase, E lsevier,2010.12(28): p. 412.[8] Martin Willemos, Bjarne Hove-Jensen and Sine Larsen, Steady State Kinetic Model for the Binding of Substrates and Allosteric Effectors to Escherichia coli Phosphoribosyl-diphosphate Synthase. The American Society for Biochemistry and Molecular Biology. 2000. 9(10): 3540835412.[9] George Ctlin Marinescu, et al, β-nicotinamide mononucleotide production in Escherichia coli. Scientific Reports, 2018. 4(12): p. 169-177.[10] Francesco Martino Carpi, Manuela Cortese, et al, Simultaneous quantifification of nicotinamide mononucleotide and related pyridine compounds in mouse tissues by UHPLCMS/MS.SSC PLUS. 2017, 12(28): 21375517.

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