Prokollagen

Prokollagen, also known as procollagen, is the intracellular and secreted precursor molecule of collagen, the main structural protein of connective tissue. It consists of three parallel alpha chains rich in glycine and proline, with non-helical N- and C-terminal propeptides that regulate assembly. Prokollagen is synthesized by collagen-producing cells such as fibroblasts, osteoblasts, and chondrocytes, encoded by COL genes (for example COL1A1 and COL1A2 for type I; COL3A1 for type III; COL2A1 for type II).

In the endoplasmic reticulum, procollagen alpha chains are translated and undergo post-translational modifications: hydroxylation of proline and lysine residues, glycosylation of hydroxylysine, chain alignment. The three chains assemble into a triple helix starting at the C-terminus and are secreted with intact propeptides.

Outside the cell, N- and C-propeptides are proteolytically removed by procollagen N- and C-proteinases, yielding tropocollagen molecules that spontaneously assemble into collagen fibrils. Lysyl oxidase then forms cross-links, increasing tensile strength.

Different procollagen types correspond to different tissues; type I is abundant in skin, bone, and tendon; type II in cartilage; type III in reticular fibers. Abnormal procollagen processing or mutations in the COL genes can cause connective tissue disorders such as osteogenesis imperfecta and Ehlers-Danlos syndrome. Vitamin C deficiency impairs hydroxylation, reducing collagen stability (scurvy).

Procollagen metabolites, such as PINP and PIIINP, serve as biomarkers of collagen synthesis in bone and connective tissue disorders and during fibrosis. Measurement can aid in diagnosis and monitoring of disease or treatment response.