Homoarginine and inhibition of human arginase activity: kinetic characterization and biological relevance.
Homoarginine and inhibition of human arginase activity: kinetic characterization and biological relevance.
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DOI：
10.1038/s41598-018-22099-x
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发表时间：
2018-02-27
影响因子：
4.6
通讯作者：
Mangoni AA
中科院分区：
文献类型：
--
作者：
Tommasi S;Elliot DJ;Da Boit M;Gray SR;Lewis BC;Mangoni AA
精氨酸酶的抑制，导致更高的精氨酸（ARG）可用于一氧化氮的合成，可能解释了高精氨酸（homarg）对动脉粥样硬化和心血管疾病的保护作用。然而，关于homarg诱导的精氨酸酶抑制在体内的意义存在不确定性。建立了一种新的UPLC-MS测定ARG转化为鸟氨酸（ORN）的方法，用于测定homarg、赖氨酸（LYS）、脯氨酸（PRO）、精氨酸（AG）、不对称二甲基精氨酸（ADMA）、对称二甲基精氨酸（SDMA）和ng -单甲基- l-精氨酸（L-NMMA）对精氨酸酶1和精氨酸酶2的抑制作用。进一步测定50名年龄在65岁之间的健康老年人（27名男性，23名女性）血浆中HOMOARG、ARG和ORN的浓度。homarg对精氨酸酶1的IC50和Ki值分别为8.14±0.52 mM和6.1±0.50 mM，对精氨酸酶2的IC50和Ki值分别为2.52±0.01 mM和1.73±0.10 mM。当使用生理homarg浓度（1-10µM）时，两种精氨酸酶同工型均保持90%的活性。在偏相关分析中，老年人血浆homarg与ARG （P = 0.38）或ARG/ORN比值（P = 0.73）无关。我们的研究结果表明精氨酸酶抑制不太可能在报道的homarg的心脏保护作用中发挥重要作用。
The inhibition of arginase, resulting in higher arginine (ARG) availability for nitric oxide synthesis, may account for the putative protective effect of homoarginine (HOMOARG) against atherosclerosis and cardiovascular disease. However, uncertainty exists regarding the significance of HOMOARG-induced arginase inhibition in vivo. A novel UPLC-MS method, measuring the conversion of ARG to ornithine (ORN), was developed to determine arginase 1 and arginase 2 inhibition by HOMOARG, lysine (LYS), proline (PRO), agmatine (AG), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and NG-Monomethyl-L-arginine (L-NMMA). Plasma HOMOARG, ARG and ORN concentrations were further measured in 50 healthy older adults >65 years (27 males and 23 females). HOMOARG inhibited arginase 1 with IC50 and Ki values of 8.14 ± 0.52 mM and 6.1 ± 0.50 mM, and arginase 2 with IC50 and Ki values of 2.52 ± 0.01 mM and 1.73 ± 0.10 mM, respectively. Both arginase isoforms retained 90% activity vs. control when physiological HOMOARG concentrations (1–10 µM) were used. In partial correlation analysis, plasma HOMOARG was not associated with ARG (P = 0.38) or ARG/ORN ratio (P = 0.73) in older adults. Our results suggest that arginase inhibition is unlikely to play a significant role in the reported cardio-protective effects of HOMOARG.
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DOI：
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发表时间：
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影响因子：
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发表时间：
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影响因子：
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