Inhibition of chick embryo lysyl oxidase by various lathyrogens and the antagonistic effect of pyridoxal.
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.
Department of Pharmacology, University of Cambridge, UK.
C I
CI
Levene
D F
DF
Sharman
B A
BA
Callingham
D000629:Aminopropionitrile / Q000494:pharmacology*; D000818:Animals; D002642:Chick Embryo; D003432:Cross-Linking Reagents; D006710:Homocysteine / Q000494:pharmacology; D007538:Isoniazid / Q000494:pharmacology*; D010396:Penicillamine / Q000494:pharmacology; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors*; D011730:Pyridoxal / Q000494:pharmacology*; D012663:Semicarbazides / Q000494:pharmacology*
D003432:Cross-Linking Reagents; D012663:Semicarbazides; D006710:Homocysteine; D000629:Aminopropionitrile; D011730:Pyridoxal; C005151:thiosemicarbazide; D008249:Protein-Lysine 6-Oxidase; D010396:Penicillamine; D007538:Isoniazid