Spry L A, Rubinstein J, Rettke C, Zenser T V, Davis B B
Veterans Administration Medical Center, GRECC, St. Louis, MO 63125.
Am J Physiol. 1988 Jan;254(1 Pt 2):F145-52. doi: 10.1152/ajprenal.1988.254.1.F145.
Renal metabolic/excretory coupling is the enhancement of urinary excretion dependent upon renal metabolism. The nitrofurothiazoles, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) and 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT), are model compounds used to study metabolic/excretory coupling. FANFT is deformylated to ANFT by renal deformylase enhancing ANFT excretion. In the rat, ANFT excretion after oral FANFT administration was 100-fold greater than ANFT excretion when ANFT was administered. FANFT and ANFT uptake into purified proximal tubules achieved equilibrium within 60 s and was demonstrated in nonviable tubules. FANFT partitioned into oil better than ANFT. Albumin inhibited FANFT and ANFT uptake into oil and decreased tubular uptake by 65%. Tubular FANFT uptake was threefold or greater than that of ANFT uptake with or without albumin. Renal deformylase was predominantly cytosolic and yielded apparent Km and Vmax of 6.7 microM and 6.1 nmol ANFT.min-1.mg protein-1, respectively. Deformylase activity was abolished by boiling, was specific for N-formylated compound, and was not altered by dinitrophenol treatment. Renal metabolic/excretory coupling for FANFT/ANFT combines energy-independent uptake with metabolism (deformylation), resulting in enhanced urinary ANFT excretion.
肾代谢/排泄偶联是指尿排泄的增强依赖于肾脏代谢。硝呋噻唑类化合物，N-[4-(5-硝基-2-呋喃基)-2-噻唑基]甲酰胺（FANFT）和2-氨基-4-(5-硝基-2-呋喃基)噻唑（ANFT），是用于研究代谢/排泄偶联的模型化合物。FANFT被肾脏去甲酰化酶去甲酰化为ANFT，从而增强ANFT的排泄。在大鼠中，口服FANFT后ANFT的排泄量比直接给予ANFT时高100倍。FANFT和ANFT被纯化的近端小管摄取在60秒内达到平衡，并且在无活力的小管中也得到证实。FANFT比ANFT更易分配到油相中。白蛋白抑制FANFT和ANFT摄取到油中，并使小管摄取减少65%。无论有无白蛋白，小管对FANFT的摄取量是对ANFT摄取量的三倍或更多。肾脏去甲酰化酶主要存在于胞质中，其表观Km和Vmax分别为6.7 microM和6.1 nmol ANFT·min-1·mg蛋白-1。去甲酰化酶活性经煮沸后消失，对N-甲酰化化合物具有特异性，且不受二硝基苯酚处理的影响。FANFT/ANFT的肾代谢/排泄偶联将能量非依赖性摄取与代谢（去甲酰化）相结合，导致尿中ANFT排泄增加。
