DIET, AROMATIC AMINO ACIDS, AND CNS NEUROTRANSMITTERS

这一竞争性更新应用程序将检查生化/代谢 食物对两个大脑合成影响的机制 神经递质、5-羟色胺(5-HT)和多巴胺(DA)。5羟色胺和多巴胺 合成速率反映了它们各自底物的大脑水平， 色氨酸(Trp)和酪氨酸(TYR)，因为限速酶 Trp和TYR羟基酶与底物不饱和。脑内色氨酸和 酪氨酸水平又受血液中酪氨酸摄取的影响。 由所有大的中性氨基酸共享的竞争性运输系统 [LNAA]，包括Trp和TYR。大脑对色氨酸的摄取也可能受到影响 通过色氨酸与血清白蛋白结合。我们对色氨酸和5-羟色胺的拟议研究将 研究食物摄入改变大脑色氨酸摄取的机制(和 5-羟色胺合成)，特别是研究膳食的重要性 蛋白质含量，通过血清LNAA水平的变化起作用，及其脂肪 含量，通过色氨酸白蛋白结合的变化起作用(餐后变化 血清中非酯化脂肪酸[NEFA]水平改变色氨酸结合 白蛋白)。我们还将研究锻炼的效果，以及它的 膳食相互作用对血清色氨酸结合、脑内色氨酸水平和5-羟色胺的影响 综合：运动提高血清NEFA水平，减少Trp结合，以及 从而提高脑内色氨酸和5-羟色胺的含量。对于TYR-&>DA，我们将把Phe作为 DA合成的底物以及Phe和TYR在生物合成中的作用 总的DA[儿茶酚胺(CAM)]合成，体外和体内。我们 还将研究苯丙氨酸和酪氨酸受体是否被大脑和肾上腺摄取 延髓，一个外周CAN神经元的模型，是相似的，以及是否 食物摄入对Phe和TYR水平(和CAM)产生类似的影响 合成)在每个站点。对于活体研究，我们将使用大鼠； 体外研究，我们将使用PC12细胞和牛肾上腺髓质 细胞。色氨酸、酪氨酸和苯丙氨酸水平，以及5-羟色胺和多巴胺合成 高效液相色谱法测定急、慢性脑和肾上腺髓质中的含量 食物摄入，或氨基酸注射，或在细胞培养中孵化 与TYR、Phe或两者同时使用。结果应该会提供一个更明确的 了解饮食似乎通知大脑的一种机制 关于最近单独消费的东西，可能是在 其他代谢事件的背景(这里指的是那些被运动刺激的事件)。 我们的数据还将增加重要的新信息，说明 酪氨酸和苯丙氨酸作为细胞间黏附分子合成的底物及饮食对细胞黏附分子合成的影响 合成，通过它在每个神经元池中产生的变化而起作用 底物。

This competing renewal application will examine biochemical/metabolic mechanisms underlying the effects of food on the synthesis of two brain neurotransmitters, serotonin (5HT) and dopamine (DA). 5HT and DA synthesis rates reflect brain levels of their respective substrates, tryptophan (TRP) and tyrosine (TYR), because the rate-limiting enzymes TRP and TYR hydroxylase are unsaturated with substrate. Brain TRP and TYR levels, in turn, are influenced by their uptake from blood, mediated by a competitive transport system shared by all large neutral amino acids [LNAA], including TRP and TYR. Brain TRP uptake may also be influenced by TRP binding to serum albumin. Our proposed studies for TRP->5HT will examine mechanisms by which food ingestion modifies brain TRP uptake (and 5HT synthesis), studying in particular the importance of the meal's protein content, acting via changes in serum LNAA levels, and its fat content, acting via changes in albumin binding of TRP (post-meal changes in serum non-esterified fatty acid [NEFA] levels alter TRP binding to albumin). We will also examine the effects of exercise, and its interaction with meals on serum TRP binding, brain TRP levels and 5HT synthesis: Exercise elevates serum NEFA levels, reduces TRP binding, and may thus raise brain TRP and 5HT. For TYR->DA, we will examine PHE as a substrate for DA synthesis, and the relative roles of PHE and TYR in overall DA [catecholamine (CAM)] synthesis, in vitro and in vivo. We will also study whether PHE and TYR uptake into brain and adrenal medulla, a model for peripheral CAN neurons, are similar, and whether food ingestion produces similar effects on PHE and TYR levels, (and CAM synthesis) at each site. For studies in vivo, we will employ rats; for studies in vitro, we will employ PC12 cells and bovine adrenal medullary cells. TRP, TYR and PHE levels, and 5HT and DA synthesis will be measured by HPLC in brain and adrenal medulla following acute or chronic food ingestion, or amino acid injection, or in cell cultures incubated with TYR, PHE or both together. Results should provide a more definitive understanding of one mechanism by which diet appears to inform the brain regarding what has recently been consumed, alone and possibly within the context of other metabolic events (here, those stimulated by exercise). Our data will also add important new information on the relative roles of TYR and PHE as substrates in CAM synthesis, and the impact of diet on CAM synthesis, acting via changes it produces in the neuronal pools of each substrate.