Stimulation of rat liver AMP-activated protein kinase by AMP analogues
Stimulation of rat liver AMP-activated protein kinase by AMP analogues
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DOI：
10.1016/0304-4165(96)00021-9
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发表时间：
1996-06-04
影响因子：
3
通讯作者：
VandenBerghe, G
中科院分区：
文献类型：
--
作者：
Henin, N;Vincent, MF;VandenBerghe, G
ZMP（5-氨基-4-咪唑甲酰胺核苷，AICAR）刺激 AMP 激活蛋白激酶（AMP-PK），ZMP（5-氨基-4-咪唑甲酰胺核苷，AICAR）是在将 AICA 核苷添加到分离的大鼠肝细胞后由腺苷激酶形成的，通过分别灭活乙酰辅酶 A 羧化酶和 3-羟基-3-甲基戊二酰辅酶 A 还原酶，从而抑制脂肪酸和胆固醇合成（Henin 等人，2015）。 (1995) FASEB J. 9, 541-546)。现在已将 ZMP 和其他 AMP 类似物的影响与 AMP 对从大鼠肝脏纯化的 AMP-PK 的影响进行了比较。 ZMP 刺激 AMP-PK 的最大程度与 AMP 相同（约 10 倍）。 ZMP 对 AMP-PK 的亲和力比 AMP 低，但这种亲和力同样受到 ATP 的影响：在 3 mM ATP 下需要 0.4 mM AMP 或 5 mM ZMP，使用 9 μM AMP 或 0.2 mM ATP 下的 0.4 mM ZMP 可以获得半最大效应。 SAMS 肽和 ATP 的 AMP-PK 动力学参数以相同的方式受到 ZMP 和 AMP 的影响。 ZMP 对 AMP-PK 的刺激与 AMP 相加，直至获得最大刺激。总而言之，这些结果表明 ZMP 与 AMP-PK 上的 AMP 结合到相同的位点。结核菌素 5'-单磷酸、2'-脱氧-AMP 和 Ara-AMP 刺激 AMP-PK，但 N-6-甲基-AMP、1,N-6-乙烯-AMP、6-巯基嘌呤核苷 5'-单磷酸、腺苷酸琥珀酸和琥珀酰-AICAR 无效，表明游离的 6-NH2 基团对于效应子与 AMP-PK 的结合可能很重要。
Stimulation of AMP-activated protein kinase (AMP-PK) by ZMP (5-amino-4-imidazolecarboxamide ribotide, AICAR), formed by adenosine kinase upon addition of AICA riboside to isolated rat hepatocytes, results in inhibition of fatty acid and cholesterol synthesis by inactivation of acetyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase, respectively (Henin et al. (1995) FASEB J. 9, 541-546). The effects of ZMP and other AMP analogues have now been compared with those of AMP on AMP-PK purified from rat liver. ZMP stimulated AMP-PK to the same maximal extent as AMP (about 10-fold). ZMP had less affinity for AMP-PK than AMP, but this affinity was similarly influenced by ATP: half-maximal effects, requiring 0.4 mM AMP or 5 mM ZMP at 3 mM ATP, were obtained with 9 mu M AMP or 0.4 mM ZMP at 0.2 mM ATP. The kinetic parameters of AMP-PK for the SAMS peptide and for ATP were influenced in the same way by ZMP and AMP. Stimulation of AMP-PK by ZMP was additive with AMP, up to when maximal stimulation was obtained. Taken together, these results indicate that ZMP binds to the same site as AMP on AMP-PK. Tubercidin 5'-monophosphate, 2'-deoxy-AMP and Ara-AMP stimulated AMP-PK, but N-6-methyl-AMP, 1,N-6-etheno-AMP, 6-mercaptopurine riboside 5'-monophosphate, adenylosuccinate and succinyl-AICAR were ineffective, suggesting that a free 6-NH2 group may be important for binding of effecters to AMP-PK.