Collagen is the body's most abundant protein, providing structural support and integrity to extracellular tissue. Collagen Synthesis involves an complex series of intracellular and extracellular processes, and occurs in a variety of cells, most commonly fibroblasts.
1. Translation of collagen alpha chains at the ribosome forms preprocollagen. Alpha chains are composed of 1⁄3 glycine, with Gly-X-Y polypeptide sequences (where X and Y are proline or lysine).
2. Hydroxylation of proline and lysine residues occurs, requiring Vitamin C (Ascorbic Acid) as a cofactor. Defects in hydroxylation can be seen in Vitamin C Deficiency (Scurvy).
3. Glycosylation of hydroxylysine residues occurs by adding glucose and galactose monomers. Afterwards, hydrogen and disulfide bonds cause three collagen glycosylated polypeptide chains to twist into a triple helix, also called procollagen. Defects in triple helix formation are seen in Osteogenesis Imperfecta.
4. Procollagen undergoes exocytosis to reach the extracellular space.
5. Cleavage of disulfide-rich terminal regions of procollagen create insoluble tropocollagen. Problems in procollagen cleavage can lead to Ehlers-Danlos Syndrome.
6. Cross-linking of adjacent tropocollagen fibrils occurs between lysine and hydroxylysine residues, forming a collagen fibril. This cross-linking requires lysyl oxidase, a copper-dependent enzyme. Defects in cross-linking can cause Ehlers-Danlos Syndrome, and may also be caused by copper deficiency, such as in Menkes Disease.
Find this Collagen Synthesis mnemonic and other mnemonics for Collagen Related Disorders among Pixorize's visual mnemonics for the USMLE Step 1 and NBME Shelf Exams.