Levene C I, Sharman D F, Callingham B A
Department of Pharmacology, University of Cambridge, UK.
Int J Exp Pathol. 1992 Oct;73(5):613-24.
Lysyl oxidase, which cross-links collagen and elastin, was obtained from chick embryo bone and cartilage and its substrate, elastin, from aorta. The enzyme was studied using an improved assay which enabled the stability of the substrate to be monitored. The enzyme was fully inhibited in vivo by beta-aminopropionitrile, semicarbazide, thiosemicarbazide and isoniazid and in vitro by beta-aminopropionitrile and semicarbazide but only partially by thiosemicarbazide and isoniazid. Penicillamine, which solubilizes collagen by labilizing Schiff base cross-links in vivo and which prevents stable cross-link formation in vitro indirectly by binding to aldehyde groups on collagen, was shown to have no direct inhibitory effect on lysyl oxidase in vivo or in vitro. Homocysteine, which also solubilizes collagen by a mechanism similar to penicillamine does not inhibit lysyl oxidase either in vivo or in vitro. Pyridoxal reversed the inhibition of lysyl oxidase by semicarbazide and isoniazid in vivo but was unable to reverse that produced by either beta-aminopropionitrile or thiosemicarbazide. These results can be explained by the presence of a sulphydryl group near the active site of lysyl oxidase, which can form a complex with the nitrile group on beta-aminopropionitrile or with the thiol group on thiosemicarbazide leading to irreversible inhibition.
赖氨酰氧化酶可使胶原蛋白和弹性蛋白发生交联，它是从鸡胚骨和软骨中提取的，其底物弹性蛋白则取自主动脉。使用一种改进的检测方法对该酶进行了研究，该方法能够监测底物的稳定性。该酶在体内可被β-氨基丙腈、氨基脲、硫代氨基脲和异烟肼完全抑制，在体外可被β-氨基丙腈和氨基脲完全抑制，但仅被硫代氨基脲和异烟肼部分抑制。青霉胺在体内通过破坏席夫碱交联来溶解胶原蛋白，在体外通过与胶原蛋白上的醛基结合间接阻止稳定交联的形成，但研究表明它在体内或体外对赖氨酰氧化酶均无直接抑制作用。同型半胱氨酸也通过与青霉胺类似的机制溶解胶原蛋白，它在体内或体外也不抑制赖氨酰氧化酶。吡哆醛可在体内逆转氨基脲和异烟肼对赖氨酰氧化酶的抑制作用，但无法逆转β-氨基丙腈或硫代氨基脲所产生的抑制作用。这些结果可以通过赖氨酰氧化酶活性位点附近存在一个巯基来解释，该巯基可与β-氨基丙腈上的腈基或硫代氨基脲上的巯基形成复合物，从而导致不可逆抑制。
