Leweling H, Breitkreutz R, Behne F, Staedt U, Striebel J P, Holm E
Department of Pathophysiology, Medical Clinic I Mannheim, University of Heidelberg, Germany.
J Hepatol. 1996 Nov;25(5):756-62. doi: 10.1016/s0168-8278(96)80249-2.
BACKGROUND/AIMS: Exogenous hyperammonemia is known to decrease the plasma levels of branched-chain amino acids (BCAA). To investigate whether changes in intracellular amino acid concentrations of muscle are associated with and may, at least in part, mediate this effect, experiments were carried out on a total of 60 male Wistar rats.
Five groups were formed in a randomized manner. Group A: no treatment; groups B1 and B2: 2-hour and 6-hour continuous central-venous infusions, respectively, of sodium salts; groups C1 and C2: 2-hour and 6-hour infusions of ammonium salts. We obtained venous blood samples and muscle biopsies. Plasma ammonia, whole blood glucose, serum insulin, blood pH, and amino acids in plasma as well as in the intracellular water of muscle were measured.
As compared with control group A, groups C1 and C2 displayed a 3.3- and a 4-fold increase, respectively, in the plasma ammonium concentration. Regarding insulin, the ammonium-infused rats were similar to group A but not to the sodium-infused B groups, which had significantly lower insulin concentrations. Administering ammonium brought about a decline in BCAA concentrations in plasma after 2 hours and in muscle after 6 hours. The ammonium-induced fall in intracellular BCAA values was preceded by an increase of glutamine as well as by a decrease of glutamate and alanine in both plasma and muscle.
It is pointed out that the inter-group differences in serum insulin, although possibly accounting for some of the findings, can by no means explain the entire pattern of amino acid concentrations seen after the ammonium infusions. Instead, our results agree with the hypothesis that hyperammonemia indirectly lowers the plasma levels of BCAA by stimulating glutamine synthesis, thus reducing the intracellular glutamate pool, which is likely to be restored, at least in part, by an intensified BCAA transamination. Clarification is needed as to whether carbon skeletons derived from valine and isoleucine additionally contribute to replenishing the glutamate pool.
背景/目的：已知外源性高氨血症会降低血浆支链氨基酸（BCAA）水平。为研究肌肉细胞内氨基酸浓度的变化是否与这种效应相关且至少部分介导了该效应，我们对总共60只雄性Wistar大鼠进行了实验。
随机分为五组。A组：不做处理；B1组和B2组：分别进行2小时和6小时的钠盐中心静脉持续输注；C1组和C2组：分别进行2小时和6小时的铵盐输注。我们采集了静脉血样本并进行肌肉活检。测量了血浆氨、全血葡萄糖、血清胰岛素、血液pH值以及血浆和肌肉细胞内水中的氨基酸。
与对照组A相比，C1组和C2组的血浆铵浓度分别升高了3.3倍和4倍。关于胰岛素，输注铵盐的大鼠与A组相似，但与输注钠盐的B组不同，B组的胰岛素浓度显著较低。输注铵盐后2小时血浆中BCAA浓度下降，6小时后肌肉中BCAA浓度下降。铵诱导的细胞内BCAA值下降之前，血浆和肌肉中的谷氨酰胺增加，谷氨酸和丙氨酸减少。
指出血清胰岛素的组间差异虽然可能解释部分结果，但绝不能解释输注铵盐后所见的氨基酸浓度的整个模式。相反，我们的结果与以下假设一致，即高氨血症通过刺激谷氨酰胺合成间接降低血浆BCAA水平，从而减少细胞内谷氨酸池，这可能至少部分通过强化BCAA转氨作用得以恢复。关于缬氨酸和异亮氨酸衍生的碳骨架是否额外有助于补充谷氨酸池，还需要进一步阐明。
