Karl P I, Tkaczevski H, Fisher S E
Department of Pediatrics and Research, North Shore University Hospital, Manhasset, New York.
Pediatr Res. 1989 Jan;25(1):19-26. doi: 10.1203/00006450-198901000-00005.
L-histidine is an essential amino acid. Its fetal-to-maternal blood concentration ratio is high, suggesting active placental transport. In this study, human placental microvillous membrane vesicles were used to characterize L-histidine transport, heretofore not evaluated in human tissue. L-Histidine uptake by microvillous membrane vesicles was stimulated by an inward sodium gradient, leading to an "overshoot," followed by apparent equilibration. Linear uptake at 22 degrees C was limited to the 1st min. The initial sodium-dependent uptake rate was proportional to the sodium concentration in the medium. The sodium-dependent uptake was markedly diminished or lost when potassium, cesium, or choline was substituted for sodium but not lithium. Replacement of chloride with sulfate or gluconate had little effect. Sodium-stimulated L-histidine uptake was further stimulated by an outward potassium gradient (inside-negative) in the presence of valinomycin. Sodium-dependent uptake kinetic constants for L-histidine were: Km = 0.44 +/- 0.18 mM: Vmax = 536 +/- 94 nmol/mg/30 s (mean +/- SD). 2-(methylamino)isobutyric acid did not inhibit L-histidine uptake. Conversely, L-histidine noncompetitively inhibited sodium-dependent uptake of 2-(methylamino)isobutyric acid and L-cysteine. L-glutamine competitively inhibited sodium-dependent L-histidine uptake. L-histidine uptake was stimulated by preloading the vesicles with either L-histidine or L-glutamine (transstimulation). L-histidine uptake was not sensitive to N-ethylmaleimide treatment but was strongly inhibited by low pH. These findings suggest that L-histidine is transported in the human placenta by a specific sodium-dependent system similar to the "N" system described in rodent hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
L-组氨酸是一种必需氨基酸。其从胎儿到母体血液的浓度比很高，表明胎盘存在活跃转运。在本研究中，使用人胎盘微绒毛膜囊泡来表征L-组氨酸的转运，此前在人体组织中尚未对其进行评估。微绒毛膜囊泡对L-组氨酸的摄取受到内向钠梯度的刺激，导致“过冲”，随后出现明显平衡。22℃时的线性摄取仅限于第1分钟。初始钠依赖性摄取速率与培养基中的钠浓度成正比。当用钾、铯或胆碱替代钠而非锂时，钠依赖性摄取明显减少或消失。用硫酸盐或葡萄糖酸盐替代氯化物影响不大。在缬氨霉素存在的情况下，外向钾梯度（内膜为负）进一步刺激了钠刺激的L-组氨酸摄取。L-组氨酸的钠依赖性摄取动力学常数为：Km = 0.44±0.18 mM；Vmax = 536±94 nmol/mg/30 s（平均值±标准差）。2-（甲氨基）异丁酸不抑制L-组氨酸摄取。相反，L-组氨酸非竞争性抑制2-（甲氨基）异丁酸和L-半胱氨酸的钠依赖性摄取。L-谷氨酰胺竞争性抑制钠依赖性L-组氨酸摄取。通过用L-组氨酸或L-谷氨酰胺预加载囊泡（转刺激）可刺激L-组氨酸摄取。L-组氨酸摄取对N-乙基马来酰亚胺处理不敏感，但受到低pH的强烈抑制。这些发现表明，L-组氨酸在人胎盘中通过一种类似于啮齿动物肝细胞中描述的“N”系统的特定钠依赖性系统进行转运。（摘要截短于250字）
