Differences between proline and lysine hydroxylations in their inhibition by zinc or by ascorbate deficiency during collagen synthesis in various cell types.
The addition of Zn2+ inhibited lysine hydroxylation markedly less effectively than it did proline hydroxylation in chick embryo tendon cells, 3T6 fibroblasts and lysyl hydroxylase-deficient Ehlers-Danlos Syndrome Type VI fibroblasts. With low Zn2+ concentrations, a similar difference was also seen in chick embryo cartilage cells, whereas with high concentrations both hydroxylations were affected to the same extent in this cell type. Ascorbate deficiency likewise had a much less effect on lysine than proline hydroxylation when studied with 3T6 fibroblasts. As these two effectors involve quite different mechanisms, it is suggested that relative insensitivity to inhibition may be a property of lysine hydroxylation seen in many cell types with a number of agents. Studies on the mechanism of the difference in the inhibition indicates that the phenomenon is probably not due to differences in the kinetic constants of Zn2+ and ascorbate for the two enzymes. Neither is it probably to any major extent due to delayed procollagen triple helix formation nor a difference in the location of the two hydroxylases within the cisternae of the rough endoplasmic reticulum. The difference similarly cannot be explained solely by an excess of lysyl hydroxylase in the cell. It may thus be due either to some other intracellular property or to the combined effect of several factors.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001206:Ascorbic Acid Deficiency / Q000201:enzymology; D002356:Cartilage / Q000201:enzymology; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D003094:Collagen / Q000096:biosynthesis*; D004535:Ehlers-Danlos Syndrome / Q000201:enzymology; D005347:Fibroblasts / Q000201:enzymology; D007700:Kinetics; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism*; D012867:Skin / Q000201:enzymology; D013710:Tendons / Q000201:enzymology; D015032:Zinc / Q000494:pharmacology*
D003094:Collagen; D006899:Mixed Function Oxygenases; D011393:Procollagen-Proline Dioxygenase; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; D015032:Zinc; D001205:Ascorbic Acid