Procollagen-proline dioxygenase

Prolyl 4-hydroxylase (4- PH) (also Procollagenprolin dioxygenase, EC 1.14.11.2 ) is a complex enzyme in eukaryotes ( Eucaryota ) which catalyzes the hydroxylation of Prolylresten proteins in animals or in tissue vertebrates. It is a post-translational modification. It is essential for the biosynthesis of collagen.

Catalyzed reaction

Using molecular oxygen (O2) are hydroxylated in some of the physiological substrate Prolylreste collagen. This is in each case an oxygen atom of α -ketoglutarate, which comprises ( by decarboxylation ) is the succinate, the other to the prolyl residue, which is the 4- hydroxyprolyl. It can run simultaneously two different reactions:

• Prolyl hydroxylation without ascorbate:

• The uncoupled decarboxylation of ketoglutarate with ascorbate (with and without the presence of Prolylrests ):

In the first reaction that is not the two atoms of an oxygen molecule to be transferred to the same substrate but in two different.

Structure

Is a tetramer of two α - and two β - subunits. The α - subunit may be encoded in humans by the three possible paralogous genes, wherein there are respective isoforms by alternative splicing. The second subunit is a protein disulfide isomerase, which, on the post-translational modification of proteins taking part, can function at a high concentration as a chaperone. She is also a subunit of the MTTP protein.

Enzyme and coenzymes

The prolyl hydroxylase is a mixed-function or dioxygenase.

In the active site is reduced iron ( Fe2 ), which can donate an electron in the short term.

Cofactors: it needs to activity α -ketoglutarate, for the regeneration of ascorbate (see ascorbic acid # Physiological significance ). Additionally, the substrate and molecular oxygen, and absence of specific inhibitors are required for activity.

Occurrence and expression

Prolylhydroxylasen are in the biosynthesis of collagen necessary, so come in all vertebrate fibroblast cells and connective tissue cells as well as many other cells, but not expressed in all cells of the body.

Stimulation / inhibition

The enzyme activity can be stimulated by bleomycin.

Prolylhydroxylasen can be specifically inhibited by poly (L- proline) by poly (ADP- ribose ) or erythropoietin (EPO, see erythropoietin # inducers of EPO synthesis).