Vilstrup Hendrik, Eriksen Peter Lykke, Kjærgaard Kristoffer, Sørensen Michael, Thomsen Karen Louise, Ott Peter
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark.
Department of Internal Medicine, Viborg Regional Hospital, Viborg, Denmark.
Metab Brain Dis. 2024 Dec 2;40(1):49. doi: 10.1007/s11011-024-01437-1.
Urea synthesis is an irreversible, essential for maintenance of health and life, and highly regulated liver function with a very high capacity for production of the end-product urea-nitrogen. The set-point of urea synthesis in relation to its overall substrate, the prevailing blood concentration of L-α-amino acids, contributes to determine whole-body nitrogen balance and the size and composition of the plasma free amino acid pool. Ammonia is definitively eliminated from the body by urea synthesis. Ammonia is released by all tissues as part of their nitrogen metabolism and accumulation of ammonia to supranormal levels is toxic, particularly to the brain where it gives rise to the devastating complication to liver diseases, hepatic encephalopathy. The first line ammonia scavenging has an efficiently high clearance several times over hepatic blood flow and close to cardiac output, under normal conditions securing rapid neutralization of ammonia by synthesis of amino acids and glutamine. This scavenging has a much lower capacity than urea synthesis. Maintenance of the scavenging system, therefore, relies on subsequent definitive depletion and elimination of amino- and amide-nitrogen to urea-nitrogen. In liver diseases, the capacity for urea synthesis is deficient due to reduced functional liver mass and dysregulation, which eventually delays the scavenging so that ammonia overflows. Considering the key role of ammonia in hepatic encephalopathy, this indirect relationship implies that deficient urea synthesis is a prerequisite for development of hyperammonemia and hepatic encephalopathy. This is in accordance with the definition of hepatic encephalopathy as being caused by liver insufficiency, where the insufficiency more specifically likely is deficiency of the urea synthesis.
尿素合成是一种不可逆的、对维持健康和生命至关重要且受到高度调节的肝功能，具有极高的终产物尿素氮生成能力。尿素合成与其总体底物（即L-α-氨基酸的当前血浓度）的设定点有助于确定全身氮平衡以及血浆游离氨基酸池的大小和组成。氨通过尿素合成从体内被彻底清除。所有组织在其氮代谢过程中都会释放氨，氨积累至超正常水平是有毒的，尤其是对大脑，会引发肝脏疾病的毁灭性并发症——肝性脑病。在正常情况下，第一线氨清除具有高效的高清除率，其清除率是肝血流量的数倍，接近心输出量，通过氨基酸和谷氨酰胺的合成确保氨的快速中和。这种清除能力比尿素合成低得多。因此，清除系统的维持依赖于随后将氨基氮和酰胺氮最终消耗并清除为尿素氮。在肝脏疾病中，由于功能性肝组织减少和调节异常，尿素合成能力不足，这最终会延迟清除，导致氨溢出。考虑到氨在肝性脑病中的关键作用，这种间接关系意味着尿素合成不足是高氨血症和肝性脑病发生的先决条件。这与肝性脑病的定义相符，即由肝功能不全引起，其中这种功能不全更具体地可能是尿素合成不足。
