Department of Anatomy and Structural Biology, University of Otago, Dunedin, New Zealand.
Neuroscience. 2009 Dec 1;164(2):611-28. doi: 10.1016/j.neuroscience.2009.08.029. Epub 2009 Aug 20.
L-arginine is metabolised by nitric oxide synthase (NOS) and arginase to form L-citrulline and nitric oxide, and L-ornithine and urea, respectively. The present study investigated NOS and arginase activities, and the levels of L-arginine, L-citrulline and L-ornithine, as well as glutamate and gamma-aminobutyric acid (GABA), in memory-related brain structures in 4, 12 and 24 months old rats. Significantly increased NOS and arginase activities with age were found across the CA1, CA2/3 and dentate gyrus (DG) sub-regions of the hippocampus and the prefrontal, entorhinal, perirhinal, postrhinal and temporal cortices in a region-specific manner. For L-arginine, there were age-related increases in CA1 and the perirhinal and temporal cortices, and decreases in the entorhinal and postrhinal cortices. L-citrulline levels were decreased with age in the prefrontal, postrhinal and temporal cortices. There were age-related decreases in L-citrulline/L-arginine molar ratio in CA1 and CA2/3 and the prefrontal and temporal cortices, but an increase in the entorhinal cortex (EC). Increased L-ornithine levels and L-ornithine/L-arginine molar ratios with age were found in most of the brain regions examined. Glutamate levels were significantly decreased with age in the prefrontal, entorhinal, perirhinal and temporal cortices, whereas GABA level was largely unchanged except for age-related increase in CA1. There were significantly decreased glutamate/GABA molar ratios with age in six brain regions. Correlational analyses revealed no inverse relationship between NOS and arginase activities, and no positive correlations between the activities of the two enzymes and the tissue concentrations of their products. Interestingly, there were significant positive correlations between glutamate and GABA, and L-arginine and its metabolites in many brain regions. These results demonstrate that the aging process has dramatic effects on the NOS and arginase metabolic pathways of L-arginine and the glutamatergic neurotransmitter system. Since L-arginine metabolism is complex, there is a need to determine its metabolomic profile in vivo in the future.
精氨酸可被一氧化氮合酶（NOS）和精氨酸酶代谢为 L-瓜氨酸和一氧化氮，以及 L-鸟氨酸和尿素。本研究调查了相关脑结构中 NOS 和精氨酸酶的活性，以及 L-精氨酸、L-瓜氨酸和 L-鸟氨酸的水平，以及谷氨酸和γ-氨基丁酸（GABA）在 4、12 和 24 个月大的大鼠中的水平。研究发现，在海马 CA1、CA2/3 和齿状回（DG）亚区以及前额叶、内嗅皮层、旁嗅皮层、后嗅皮层和颞叶皮层中，NOS 和精氨酸酶的活性随着年龄的增长呈区域特异性显著增加。L-精氨酸在 CA1 和旁嗅皮层和颞叶皮层中随年龄增长而增加，而在内嗅皮层和后嗅皮层中减少。L-瓜氨酸水平随年龄增长在前额叶、后嗅皮层和颞叶皮层中降低。L-瓜氨酸/L-精氨酸摩尔比在 CA1 和 CA2/3 以及前额叶和颞叶皮层中随年龄相关下降，但在内嗅皮层中增加。在大多数检查的脑区中，L-鸟氨酸水平和 L-鸟氨酸/L-精氨酸摩尔比随年龄增长而增加。谷氨酸水平在前额叶、内嗅皮层、旁嗅皮层和颞叶皮层中随年龄显著降低，而 GABA 水平基本不变，除 CA1 中与年龄相关的增加外。六个脑区的谷氨酸/GABA 摩尔比随年龄下降。相关分析显示，NOS 和精氨酸酶的活性之间没有反比关系，两种酶的活性与它们的产物的组织浓度之间没有正相关。有趣的是，在许多脑区中，谷氨酸和 GABA 以及 L-精氨酸及其代谢物之间存在显著的正相关关系。这些结果表明，衰老过程对 L-精氨酸的 NOS 和精氨酸酶代谢途径以及谷氨酸能神经递质系统有显著影响。由于 L-精氨酸代谢复杂，未来需要确定其在体内的代谢组学图谱。
