Formation and Composition of Collagen

Like members of most families, the collagens share certain similarities but also possess characteristic differences. To date, 28 types of collagen macromolecules have been identified. The most abundant, type I collagen, is found in skin, fasciae, tendons, ligaments, and bones. Type II collagen is found in all forms of hyaline cartilage (including growth plate and articular cartilage) and in the nucleus pulposus of the intervertebral disc. Type III collagen is less abundant but is generally found with type I collagen. Type IV collagen, the most abundant nonfibrillar type, is a major constituent of the basement membrane. Type V collagen, the least abundant fibrillar collagen, is found in the placenta and blood vessels. In addition, there is a variety of minor collagens whose distribution and function are still being investigated.

All collagen molecules are composed of three polypeptide α chains wrapped around one another like a three-stranded rope.

Although each collagen type is a unique combination of three α chains (in the form of either a homotrimer or a heterotrimer) and although each α chain is encoded by a unique gene and possesses a unique amino acid sequence, there are many similarities among the various types. Each α chain has a primary structure that is relatively simple and highly repetitive; a good example is glycine-X-Y334. Glycine, the amino acid having the smallest side-chain, occupies every third amino acid position, and X and Y are often proline and hydroxyproline, respectively. This repeating triplet allows the α chains to form a tight helix.

Despite the relatively simple structure of collagen, its biosynthetic pathway is complex and can be divided into intracellular and extracellular events. The intracellular assembly begins with the transcription of messenger ribonucleic acid (mRNA) from collagen genes. The pro-α chains of procollagen are synthesized on the rough endoplasmic reticulum by translation of the corresponding mRNA. Subsequently, many post-translational modifications occur. Hydroxylation of specific proline and lysine residues takes place in the lumen of the rough endoplasmic reticulum while the still-growing α chains are attached to ribosomes. This process requires the presence of vitamin C, oxygen, ferrous iron, α-ketoglutarate, and the appropriate hydroxylation enzymes—prolyl 4-hydroxylase, prolyl 3-hydroxylase, and lysyl hydroxylase. Deficiencies in cofactors or enzymes can lead to deficits in secretion. Other post-translational modifications involve glycosylation of hydroxylysine residues, glycosylation of the carboxyl (C)-terminal propeptide, and formation of disulfide bonds among the C-terminal propeptides of the three α chains. The last process initiates the formation of the triple helix in the lumen of the rough endoplasmic reticulum. Once the triple helix is formed, procollagen is transported from the rough endoplasmic reticulum to the Golgi apparatus and packaged for secretion by exocytosis.

Once outside the cell, the C-terminal and N-terminal propeptides of some collagens are cleaved by procollagen peptidase C and procollagen peptidase N, respectively. Following cleavage of the terminal propeptides, these collagen molecules spontaneously precipitate as fibrils under physiologic conditions. The 68-nm periodic staining of fibrillar collagen results from the staggered structure of the fibrils. Collagen structures are stabilized by intermolecular crosslinking between lysine or hydroxylysine residues in adjacent collagen molecules.

As the major component of the connective tissue matrix, collagen determines the tensile strength of tissues, provides the framework for tissues, limits the movement of other components of tissue and matrix, induces platelet aggregation and clot formation, regulates the deposition of hydroxyapatite crystals in bone, and plays an important role in the regulation and differentiation of various cells and tissues.

Heritable disorders of collagen metabolism include Ehlers-Danlos syndrome, Marfan syndrome, and osteogenesis imperfecta. Acquired disorders include scurvy, keloid formation, proliferative scar formation, atherosclerosis, pulmonary fibrosis, and cirrhosis.

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Jul 3, 2016 | Posted by in MUSCULOSKELETAL MEDICINE | Comments Off on Formation and Composition of Collagen

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