Loh Y P, Parish D C, Tuteja R
J Biol Chem. 1985 Jun 25;260(12):7194-205.
Pro-opiomelanocortin (adrenocorticotropin/endorphin prohormone) is processed to yield active hormones by cleavages at paired basic amino acid residues. In this study, an enzyme that specifically cleaves at the paired basic residues of this prohormone has been purified from bovine pituitary intermediate lobe secretory vesicles, the intracellular processing site of proopiomelanocortin. This enzyme, named pro-opiomelanocortin converting enzyme, has been characterized as a glycoprotein of Mr approximately 70,000. It has an apparent isoelectric point between 3.5 and 4.0. The pH optimum of the pro-opiomelanocortin converting enzyme is between 4 and 5, but the enzyme is highly active at the intravesicular pH of 5.1-5.6. The enzyme specifically cleaved the Lys-Arg pairs of pro-opiomelanocortin to yield Mr = to 21,000-23,000 ACTH, beta-lipotropin, Mr 13,000 and 4,500 ACTH, beta-endorphin, and a Mr = 16,000 NH2-terminal glycopeptide, the products synthesized by the pituitary intermediate lobe in situ. NH2- and COOH-terminal analysis of the products indicated that the pro-opiomelanocortin converting enzyme cleaves the peptide bond either between the Lys and Arg or on the carboxyl side of the Arg at Lys-Arg pairs of pro-opiomelanocortin. The intracellular localization, pH optimum, and cleavage specificity of the enzyme suggest that it may function as a pro-opiomelanocortin processing enzyme in the pituitary intermediate lobe in vivo.
阿片促黑激素皮质素原（促肾上腺皮质激素/内啡肽前体激素）通过在成对碱性氨基酸残基处的切割加工产生活性激素。在本研究中，一种特异性切割该前体激素成对碱性残基的酶已从牛垂体中间叶分泌囊泡中纯化出来，该囊泡是阿片促黑激素皮质素原的细胞内加工位点。这种酶被命名为阿片促黑激素皮质素原转化酶，其特征是一种分子量约为70,000的糖蛋白。它的表观等电点在3.5至4.0之间。阿片促黑激素皮质素原转化酶的最适pH在4至5之间，但该酶在囊泡内pH为5.1 - 5.6时具有高活性。该酶特异性切割阿片促黑激素皮质素原的Lys - Arg对，产生分子量为21,000 - 23,000的促肾上腺皮质激素、β - 促脂素、分子量为13,000和4,500的促肾上腺皮质激素、β - 内啡肽以及分子量为16,000的NH2 - 末端糖肽，这些都是垂体中间叶原位合成的产物。对产物的NH2 - 和COOH - 末端分析表明，阿片促黑激素皮质素原转化酶在阿片促黑激素皮质素原的Lys - Arg对处，在Lys和Arg之间或Arg的羧基侧切割肽键。该酶的细胞内定位、最适pH和切割特异性表明它可能在体内垂体中间叶中作为阿片促黑激素皮质素原加工酶发挥作用。
