Inhibition of hydroxyproline synthesis by palladium ions.
Palladium ions, administered as PdSO4, markedly affect the incorporation of L-[3,4-3H2] proline into non-dialyzable fractions in 10-day chick embryo cartilage explants with a 55-65% reduction in the concentration range 0.06-0.6 mM. Under these conditions the synthesis of [3H]hydroxyproline was nearly completely inhibited. Experiments with prolyl hydroxylase (EC 1.14.11.2) indicated a strong irreversible inhibition of the enzyme with a competition between Fe2+ and Pd2+. The Ki for the inhibition was 0.02 mM. Pd2+-treated enzyme remained inactive after extensive dialysis. These studies suggest that Pd2+ may inhibit collagen synthesis by replacing Fe2+ in the active site of prolyl hydroxylase and forming strong complexes with the enzyme. These studies also point to a potential mechanism of Pd2+ toxicity.
D000818:Animals; D001665:Binding Sites; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism*; D002642:Chick Embryo; D006909:Hydroxyproline / Q000096:biosynthesis*; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D010165:Palladium / Q000494:pharmacology*; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors; D011392:Proline / Q000378:metabolism; D011485:Protein Binding
D010165:Palladium; D011392:Proline; D007501:Iron; D011393:Procollagen-Proline Dioxygenase; D006909:Hydroxyproline