The Novel Type II Prolyl 4-Hydroxylase Is the Main Enzyme Form in Chondrocytes and Capillary Endothelial Cells, whereas the Type I Enzyme Predominates in Most Cells

Procollagen-proline dioxygenase (EC 1.14.11.2), an alpha2beta2 tetramer in vertebrates, plays a central role in the synthesis of all collagens. Recently an isoform of the alpha subunit, the alpha(II) subunit, was characterized in man and mouse and found to form a tetramer with the same beta subunit as the previously known alpha(I) subunit. We report here that the (alpha(I))2beta2 type I tetramer is the main enzyme form in most cell types and tissues and that its contribution to total prolyl 4-hydroxylase activity in cultured cells increases in confluence. Surprisingly, however, the (alpha(II))2beta2 type II enzyme was found to represent at least about 70% of the total prolyl 4-hydroxylase activity in cultured mouse chondrocytes and about 80% in mouse cartilage, the corresponding percentage in mouse bone being about 45% and that in many other mouse tissues about 10% or less. Immunofluorescence studies on samples from a fetal human foot confirmed these data and additionally indicated that the type II enzyme represents the main or only enzyme form in capillary endothelial cells. Thus the type II prolyl 4-hydroxylase is likely to play a major role in the development of cartilages and cartilaginous bones and also of capillaries.