Type IX Ehlers-Danlos syndrome and Menkes syndrome: the decrease in lysyl oxidase activity is associated with a corresponding deficiency in the enzyme protein.
Type IX of the Ehlers-Danlos syndrome (E-D IX) and the Menkes syndrome are X-linked recessively inherited disorders characterized by abnormalities in copper metabolism. These abnormalities are associated with a severe reduction in the activity of lysyl oxidase, the extracellular copper enzyme that initiates crosslinking of collagens and elastin. No increase in this deficient enzyme activity was obtained when culture media from fibroblasts of patients with E-D IX or the Menkes syndrome were incubated with copper under various conditions in vitro. A distinct, although small, increase in lysyl oxidase activity was obtained, however, when copper-supplemented media were used during culturing of the fibroblasts, although even under these conditions, the enzyme activity in the media from the affected cells remained markedly below that of the controls. Immunoprecipitation, dot-blotting, and immunoperoxidase staining experiments with antisera to human lysyl oxidase indicated that fibroblasts from patients with E-D IX or the Menkes syndrome do not secrete into their medium, or contain inside the cell, any significant amounts of a copper-deficient, catalytically inactive lysyl oxidase protein. These findings appear to be consistent with the hypothesis that synthesis of the lysyl oxidase protein itself is impaired. The possibility is not excluded, however, that a copper-deficient enzyme protein may be synthesized in normal amounts but become degraded very rapidly inside the cell. The failure to obtain any large increase in the deficient lysyl oxidase activity upon various forms of copper administration suggests that it may not be possible to obtain any significant improvement in the connective tissue manifestations of these disorders by copper therapy.
Kuivaniemi
H
H
University of Oulu, Department of Medical Biochemistry, Finland.
Peltonen
L
L
Kivirikko
K I
KI
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology; D003470:Culture Media; D004535:Ehlers-Danlos Syndrome / Q000201:enzymology*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000201:enzymology*; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism
D003470:Culture Media; D003300:Copper; D008249:Protein-Lysine 6-Oxidase