Rieder R F
J Clin Invest. 1971 Feb;50(2):388-400. doi: 10.1172/JCI106506.
Hemoglobin Gun Hill is an unstable mutant hemoglobin associated with mild compensated hemolysis. This abnormal protein has a deletion of five amino acids in the beta-chains. The deletion includes the heme-binding proximal histidine at position 92. The beta-chains of hemoglobin Gun Hill lack heme groups. Approximately 32% of the circulating hemoglobin in heterozygous subjects consists of the mutant hemoglobin. When reticulocytes were incubated with radioactive amino acid the specific activity of hemoglobin Gun Hill was three to six times that of hemoglobin A. Total incorporation of radioactivity into hemoglobin Gun Hill was two to three times that into hemoglobin A. There were 20-50% more total counts in beta-Gun Hill (beta(GH)) than in beta(A). These results indicate that in reticulocytes there was greater synthesis of the abnormal beta-chains than beta(A)-chains. The ratio of the specific activities of the alpha-chains of hemoglobin Gun Hill to the alpha-chains of hemoglobin A was 20: 1. There was evidence of a free pool of alpha-chains in the reticulocytes containing hemoglobin Gun Hill. After 10 min of incubation approximately 40% of the total alpha-chain radioactivity was in the free pool. When protein synthesis was blocked by incubation of reticulocytes with puromycin, the specific activity of the alpha-chains of hemoglobin Gun Hill continued to increase due to direct exchange of alpha-subunits between the free pool and preformed hemoglobin Gun Hill. Studies of the assembly of beta(A) and beta(GH) revealed that the rates of translation of the two polypeptide chains were equal and uniform. No evidence was obtained for the existence of "slow points" in the process of globin chain assembly. The studies also suggest that lack of strong heme-globin binding does not hinder the synthesis of globin chains.
冈希尔血红蛋白是一种与轻度代偿性溶血相关的不稳定突变血红蛋白。这种异常蛋白在β链中有五个氨基酸缺失。缺失包括位于92位的与血红素结合的近端组氨酸。冈希尔血红蛋白的β链缺乏血红素基团。杂合子受试者循环血红蛋白中约32%由突变血红蛋白组成。当网织红细胞与放射性氨基酸一起孵育时，冈希尔血红蛋白的比活性是血红蛋白A的三到六倍。放射性物质掺入冈希尔血红蛋白的总量是掺入血红蛋白A的两到三倍。β-冈希尔（β(GH)）中的总计数比β(A)中的多20 - 50%。这些结果表明，在网织红细胞中，异常β链的合成比β(A)链更多。冈希尔血红蛋白α链与血红蛋白Aα链的比活性之比为20:1。有证据表明含有冈希尔血红蛋白的网织红细胞中有α链的自由池。孵育10分钟后，约40%的总α链放射性存在于自由池中。当用嘌呤霉素孵育网织红细胞来阻断蛋白质合成时，冈希尔血红蛋白α链的比活性由于自由池与预先形成的冈希尔血红蛋白之间α亚基的直接交换而继续增加。对β(A)和β(GH)组装的研究表明，两条多肽链的翻译速率相等且均匀。在珠蛋白链组装过程中未获得存在“慢位点”的证据。这些研究还表明，缺乏强的血红素-珠蛋白结合并不阻碍珠蛋白链的合成。
