Page A E, Fuller K, Chambers T J, Warburton M J
Department of Histopathology, St. George's Hospital Medical School, London, United Kingdom.
Arch Biochem Biophys. 1993 Nov 1;306(2):354-9. doi: 10.1006/abbi.1993.1523.
Tripeptidyl peptidase I (EC 3.4.14.9), which cleaves tripeptides from the N-terminus of synthetic substrates, has been purified from human osteoclastomas (a bone tumor containing large numbers of normal osteoclasts). The enzyme has an M(r) of 48 kDa but forms aggregates with an M(r) of about 700 kDa. The tripeptidyl peptidase has an acidic pH optimum (approximately pH 5.0), suggesting that it has a lysosomal localization and prefers substrates with a hydrophobic amino acid in the P1 position. There is an absolute requirement for a nonsubstituted N-terminus. The enzyme is inhibited by reagents which modify serine and histidine residues. Lysosomal tripeptidyl peptidase is known to be capable of cleaving Gly-Pro-X triplets from synthetic collagen-like polypeptides. Ala-Ala-Phe-CH2Cl, a potent inhibitor of osteoclastoma tripeptidyl peptidase, inhibits osteoclastic bone resorption in an in vitro test system. This suggests that tripeptidyl peptidase I, secreted by osteoclasts, is involved at some stage in the degradation of bone collagen.
三肽基肽酶I（EC 3.4.14.9）可从合成底物的N端切割三肽，已从人骨巨细胞瘤（一种含有大量正常破骨细胞的骨肿瘤）中纯化得到。该酶的相对分子质量为48 kDa，但会形成相对分子质量约为700 kDa的聚集体。三肽基肽酶的最适pH呈酸性（约pH 5.0），这表明它定位于溶酶体，且更倾向于作用于P1位带有疏水氨基酸的底物。其对未被取代的N端有绝对需求。该酶会被修饰丝氨酸和组氨酸残基的试剂抑制。已知溶酶体三肽基肽酶能够从合成的胶原样多肽中切割Gly-Pro-X三联体。丙氨酰-丙氨酰-苯丙酰-氯甲烷，一种骨巨细胞瘤三肽基肽酶的强效抑制剂，在体外测试系统中可抑制破骨细胞的骨吸收。这表明破骨细胞分泌的三肽基肽酶I在骨胶原降解的某个阶段发挥作用。
