Gietzen Dorothy W
Department of Anatomy, Physiology and Cell Biology, University of California, Davis, CA 95616, USA.
J Clin Med. 2021 Dec 30;11(1):191. doi: 10.3390/jcm11010191.
Our health requires continual protein synthesis for maintaining and repairing tissues. For protein synthesis to function, all the essential (indispensable) amino acids (IAAs) must be available in the diet, along with those AAs that the cells can synthesize (the dispensable amino acids). Here we review studies that have shown the location of the detector for IAA deficiency in the brain, specifically for recognition of IAA deficient diets (IAAD diets) in the anterior piriform cortex (APC), with subsequent responses in downstream brain areas. The APC is highly excitable, which makes is uniquely suited to serve as an alarm for reductions in IAAs. With a balanced diet, these neurons are kept from over-excitation by GABAergic inhibitory neurons. Because several transporters and receptors on the GABAergic neurons have rapid turnover times, they rely on intact protein synthesis to function. When an IAA is missing, its unique tRNA cannot be charged. This activates the enzyme General Control Nonderepressible 2 (GCN2) that is important in the initiation phase of protein synthesis. Without the inhibitory control supplied by GABAergic neurons, excitation in the circuitry is free to signal an urgent alarm. Studies in rodents have shown rapid recognition of IAA deficiency by quick rejection of the IAAD diet.
我们的健康需要持续的蛋白质合成来维持和修复组织。为使蛋白质合成发挥作用，饮食中必须含有所有必需（不可或缺）氨基酸（IAA），以及细胞能够合成的那些氨基酸（非必需氨基酸）。在此，我们回顾了一些研究，这些研究表明大脑中IAA缺乏检测器的位置，特别是在前梨状皮质（APC）中对IAA缺乏饮食（IAAD饮食）的识别，以及随后在下游脑区的反应。APC高度易兴奋，这使其特别适合作为IAA减少的警报器。在均衡饮食的情况下，这些神经元会被γ-氨基丁酸能抑制性神经元抑制，从而避免过度兴奋。由于γ-氨基丁酸能神经元上的几种转运体和受体周转时间很快，它们依赖完整的蛋白质合成来发挥功能。当一种IAA缺失时，其独特的转运RNA无法被加载。这会激活在蛋白质合成起始阶段起重要作用的一般控制非抑制性2（GCN2）酶。没有γ-氨基丁酸能神经元提供的抑制控制，回路中的兴奋就会自由地发出紧急警报。对啮齿动物的研究表明，通过快速拒绝IAAD饮食，它们能迅速识别IAA缺乏。
