Roth K S, Medow M S, Moses L C, Spencer P D, Schwarz S M
Department of Pediatrics, Medical College of Virginia, Richmond 23298.
Biochim Biophys Acta. 1989 Dec 11;987(1):38-46. doi: 10.1016/0005-2736(89)90452-5.
Using succinylacetone (SA), a metabolite of tyrosine excreted in excess by infants and children with hereditary tyrosinemia and the renal Fanconi syndrome (FS), we have investigated developmentally-related membrane transport events leading to emergence of the generalized renal tubular dysfunction seen in human FS. SA was found to impair sugar and amino acid uptake by both newborn renal tubules and 7-day renal brush-border membrane vesicles (BBMV). This impairment by SA was due in part to a slowing of substrate cotransport rate of 22Na+-entry into BBMV. Concentration-dependent uptake studies indicated SA inhibited the newborn high-affinity transport systems for sugars and amino acids. SA also caused an increase in membrane fluidity and a shift in the thermotropic transition temperature. The demonstrated dual nature of SA's effect on membrane fluidity and O2 consumption, together with the relative contribution of each component to SA-induced transport impairment helps to provide a basis for an understanding of the age-related increases in glucosuria, aminoaciduria and natriuria seen in infants with FS.
利用琥珀酰丙酮（SA），一种患有遗传性酪氨酸血症和肾范科尼综合征（FS）的婴幼儿过量排泄的酪氨酸代谢产物，我们研究了与发育相关的膜转运事件，这些事件导致了人类FS中出现的全身性肾小管功能障碍。研究发现，SA会损害新生肾小管和7日龄肾刷状缘膜囊泡（BBMV）对糖和氨基酸的摄取。SA造成的这种损害部分是由于22Na+进入BBMV的底物共转运速率减慢。浓度依赖性摄取研究表明，SA抑制了新生肾小管对糖和氨基酸的高亲和力转运系统。SA还导致膜流动性增加以及热致转变温度发生偏移。SA对膜流动性和氧气消耗影响的双重特性，以及各组分对SA诱导的转运损害的相对贡献，有助于为理解FS婴儿中与年龄相关的糖尿、氨基酸尿和钠尿增加提供依据。
