Prolyl 4-hydroxylase (EC 1.14.11.2 ) plays a central role in collagen synthesis. It catalyzes the formation of
4-hydroxyproline in collagens by hydroxylation of proline residues in peptide linkages. The 4-hydroxyproline residues are
essential for the folding of the newly synthesized procollagen polypeptide chain into triple helical molecules. The active
enzyme is a tetramer of 2 alpha and 2 beta subunits with a molecular weight of about 240,000. The beta subunit (P4HB;
) is identical to the enzyme disulfide isomerase (EC 5.3.4.1 ) and a major cellular thyroid-binding protein. The alpha
subunit probably contributes a major part of the catalytic site of the enzyme. Helaakoski et al. (1989) isolated cDNA clones
for the alpha subunit. They found that the clones encode a polypeptide of 517 amino acid residues and a signal peptide of 17
amino acids.
General function
Enzyme, Oxidoreductase
Comment
Cellular localization
Extracellular Matrix, Secreted
Comment
Ovarian function
Ovulation
Comment
Nagai R et al 1998 reported spatio-temporal changes of prolyl 4-hydroxylase in granulosa cells during
ovulation in eCG-hCG-treated immature rat ovaries. The immunolocalization of prolyl 4-hydroxylase (PHase), a key enzyme of collagen synthesis, and the
effects of anti-progesterone RU486 on PHase during the ovulatory process in eCG-hCG-treated
immature rat ovaries were studied to investigate the mechanisms of tissue repair in follicle walls after
follicular rupture. No obvious immunolocalization of PHase was observed in theca cells
throughout the ovulatory process except just after follicular rupture. In contrast, in granulosa cells,
PHase was first observed at 9 h after the hCG injection, and the staining intensity apparently increased
from 9 to 15 h, especially around the apex of preovulatory follicles and the orifice of ruptured
follicles. Consistent with these observations, PHase concentration in granulosa cells isolated from the
ovaries significantly increased by 9 h (0.45 +/- 0.03 pg per cell), and reached a peak at 15 h (0.66 +/-
0.06 pg per cell) after the hCG injection. This peak was inhibited when 20 mg RU486 kg-1 was
administered at 8 h. The results suggest that PHase expressed in granulosa cells may play an important role in the repair of
ruptured follicle walls, via progesterone-dependent PHase production.
Expression regulated by
LH, Steroids
Comment
Ovarian localization
Granulosa, Theca, Surface epithelium
Comment
Auersperg N, reported that prolyl 4-hydroxylase is present in cultured human ovarian surface epithelial cells.