Brosnan Margaret E, Brosnan John T
Department of Biochemistry, Memorial University of Newfoundland, St John's, Canada.
Am J Clin Nutr. 2009 Sep;90(3):857S-861S. doi: 10.3945/ajcn.2009.27462Z. Epub 2009 Jul 22.
Glutamate plays a central role in hepatic amino acid metabolism, both because of its role in the transdeamination of most amino acids and because the catabolism of arginine, ornithine, proline, histidine, and glutamine gives rise to glutamate. It is now appreciated that different hepatic functions are restricted to hepatocyte subpopulations within different acinar zones. This is also a feature of glutamate metabolism. Glutamine catabolism and synthesis are physically separated by zonation, with glutamine synthetase restricted to a narrow band of hepatocytes in zone 3 of the hepatic acinus, whereas glutaminase occurs in zone 1. Arginine and ornithine metabolism is also restricted to particular hepatocyte subpopulations. Ornithine aminotransferase, the regulated enzyme of arginine and ornithine catabolism, is restricted to the same zone 3 cells as glutamine synthetase, whereas the urea cycle is found in the remaining hepatocytes. This separation facilitates the independent regulation of these 2 different metabolic processes. We know the acinar localization of only a small fraction of the approximately 15,000 genes expressed in the liver. Knowledge of the acinar localization of metabolic processes is essential for an appreciation of their relation to other hepatic functions and their regulation.
谷氨酸在肝脏氨基酸代谢中起着核心作用,这既是因为它在大多数氨基酸的转氨脱氨基过程中发挥作用,也是因为精氨酸、鸟氨酸、脯氨酸、组氨酸和谷氨酰胺的分解代谢会产生谷氨酸。现在人们认识到,不同的肝脏功能局限于不同腺泡区内的肝细胞亚群。这也是谷氨酸代谢的一个特点。谷氨酰胺的分解代谢和合成在区域上是分开的,谷氨酰胺合成酶局限于肝腺泡3区的一小条带肝细胞中,而谷氨酰胺酶则出现在1区。精氨酸和鸟氨酸的代谢也局限于特定的肝细胞亚群。鸟氨酸转氨酶是精氨酸和鸟氨酸分解代谢的调节酶,与谷氨酰胺合成酶一样局限于3区的同一批细胞中,而尿素循环则存在于其余的肝细胞中。这种分隔有助于对这两个不同代谢过程进行独立调节。我们仅了解肝脏中大约15000个表达基因中一小部分的腺泡定位。了解代谢过程的腺泡定位对于理解它们与其他肝脏功能及其调节之间的关系至关重要。