Expression of two succinyl-CoA synthetases with different nucleotide specificities in mammalian tissues

Expression of two succinyl-CoA synthetases with different nucleotide specificities in mammalian tissues
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DOI:
10.1074/jbc.m406884200
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发表时间:
2004-08-27
影响因子:
4.8
通讯作者:
Milavetz, BI
Milavetz, BI
中科院分区:
生物学2区
文献类型:
--
作者:
Lambeth, DO;Tews, KN;Milavetz, BI

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近50年来,动物体内的琥珀酰辅酶A合成酶被认为是鸟嘌呤核苷酸的专一性酶。最近,我们从鸽子的胸肌和肝脏中提纯并鉴定了形成ADP的琥珀酰辅酶A合成酶(Johnson,J.D.,Muhonen,W.W.和Lambeth,D.O.(1998)J.Biol)。化学。273、27573-27579)。在BLAST搜索中使用鸽子酶的序列作为查询,我们获得了这两种酶在广泛的动物物种(Johnson,J.D.,Mehus,J.G.,Tews,K.,Milavetz,B.I.和Lambeth,D.O.(1998)J.Biol)中表达的遗传证据。化学。273、27580-27586)。在这里,我们通过提供来自Western和Northern blotts和酶分析的数据来扩展这些观察结果,表明这两种蛋白在哺乳动物中广泛表达,其相对数量因组织而异。我们认为,两种琥珀酰辅酶A合成酶都催化柠檬酸循环中的反向反应,其中ADP形成酶增加ATP的产生,而GDP形成酶支持GTP依赖的合成代谢过程。被广泛接受的穿梭机制被用来解释P-烯醇式丙酮酸如何通过线粒体膜运输在细胞质和线粒体基质之间转移高能磷酸盐。
For nearly 50 years, succinyl-CoA synthetase in animals was thought to be specific for guanine nucleotides. Recently, we purified and characterized both an ADP-forming succinyl-CoA synthetase from pigeon breast muscle and the GDP-forming enzyme from liver (Johnson, J. D., Muhonen, W. W., and Lambeth, D. O. (1998) J. Biol. Chem. 273, 27573-27579). Using the sequences of the pigeon enzymes as queries in BLAST searches, we obtained genetic evidence that both enzymes are expressed in a wide range of animal species (Johnson, J. D., Mehus, J. G., Tews, K., Milavetz, B. I., and Lambeth, D. O. (1998) J. Biol. Chem. 273, 27580-27586). Here we extend those observations by presenting data from Western and Northern blots and enzymatic assays showing that both proteins are widely expressed in mammals with the relative amounts varying from tissue to tissue. We suggest that both succinyl-CoA synthetases catalyze the reverse reaction in the citric acid cycle in which the ADP-forming enzyme augments ATP production, whereas the GDP-forming enzyme supports GTP-dependent anabolic processes. Widely accepted shuttle mechanisms are invoked to explain how transport of P-enolpyruvate across mitochondrial membranes can transfer high energy phosphate between the cytosol and mitochondrial matrix.