Foreman J W, Wald H, Blumberg G, Pepe L M, Segal S
Metabolism. 1982 Jun;31(6):613-9. doi: 10.1016/0026-0495(82)90101-9.
Isolated rat renal cortical tubules were used to study the nature of homocystine entry into the tubule cell and its transport interactions with cystine and the dibasic amino acids. The uptake of homocystine with time was progressive, reaching a steady state after 60 min. of incubation. Analysis of the intracellular pool after 5 and 30 min. of incubation revealed that virtually all of the transported homocystine had been converted to other metabolites of the transsulfuration pathway. The major metabolite was cystathionine with a somewhat lesser, but still significant amount as S-adenosylhomocysteine. A kinetic analysis showed that two systems for cellular entry of homocysteine existed with a Km1 of 0.17 mM and a Km2 of 7.65 mM. Arginine and lysine inhibited homocystine uptake via the low Km, high affinity system, but appeared not to inhibit the high Km, low affinity system. Cystine inhibited the low Km, high affinity system, but had an indeterminate effect on the high Km, low affinity system. Homocystine inhibited the uptake of cystine, lysine and arginine by isolated rat renal cortical tubules. The inhibition of homocystine on cystine uptake appeared to occur on both the high and low Km system for tubule cell entry of cystine. The data suggest that the low Km system for homocystine transport is shared with cystine and the dibasic amino acids. These data extend the knowledge of homocystine metabolism and provide a rational basis for new approaches to the treatment of homocystinuria.
采用分离的大鼠肾皮质肾小管来研究同型胱氨酸进入肾小管细胞的性质及其与胱氨酸和二碱基氨基酸的转运相互作用。同型胱氨酸的摄取随时间逐渐增加，孵育60分钟后达到稳态。孵育5分钟和30分钟后对细胞内池进行分析，结果显示几乎所有转运的同型胱氨酸都已转化为转硫途径的其他代谢产物。主要代谢产物是胱硫醚，作为S-腺苷同型半胱氨酸的量略少，但仍很显著。动力学分析表明，存在两种细胞摄取同型半胱氨酸的系统，Km1为0.17 mM，Km2为7.65 mM。精氨酸和赖氨酸通过低Km、高亲和力系统抑制同型胱氨酸的摄取，但似乎不抑制高Km、低亲和力系统。胱氨酸抑制低Km、高亲和力系统，但对高Km、低亲和力系统的影响不确定。同型胱氨酸抑制分离的大鼠肾皮质肾小管对胱氨酸、赖氨酸和精氨酸的摄取。同型胱氨酸对胱氨酸摄取的抑制似乎发生在肾小管细胞摄取胱氨酸的高Km和低Km系统上。这些数据表明，同型胱氨酸转运的低Km系统与胱氨酸和二碱基氨基酸共用。这些数据扩展了对同型胱氨酸代谢的认识，并为同型胱氨酸尿症的新治疗方法提供了合理依据。
