collagen metabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways involving collagen, any of a group of fibrous proteins of very high tensile strength that form the main component of connective tissue in animals. Collagen is highly enriched in glycine (some regions are 33% glycine) and proline, occurring predominantly as 3-hydroxyproline (about 20%). [GOC:mah, ISBN:0198506732]

Collagen metabolism is a complex and vital biological process responsible for the synthesis, assembly, and degradation of collagen, a fibrous protein that provides structural support and integrity to tissues throughout the body. This process involves numerous steps and several key players, including:

**1. Transcription and Translation:**
* The process begins with the transcription of collagen genes into messenger RNA (mRNA) in the nucleus.
* mRNA then travels to ribosomes in the cytoplasm, where it is translated into collagen polypeptide chains.
* These chains are called pro-alpha chains, which are precursor molecules to mature collagen.

**2. Modification and Assembly:**
* Pro-alpha chains undergo several post-translational modifications, including hydroxylation of proline and lysine residues, and glycosylation.
* These modifications are crucial for proper folding and assembly of collagen molecules.
* Hydroxylation involves the addition of hydroxyl groups to specific amino acids, requiring the presence of enzymes like prolyl hydroxylase and lysyl hydroxylase.
* Glycosylation involves the addition of sugar molecules to hydroxylysine residues, facilitated by glycosyltransferases.
* The modified pro-alpha chains associate with each other to form procollagen molecules, which consist of three polypeptide chains arranged in a triple helix structure.

**3. Exocytosis and Extracellular Assembly:**
* Procollagen molecules are transported to the Golgi apparatus, where they undergo further processing and packaging into secretory vesicles.
* These vesicles migrate to the cell membrane and release procollagen into the extracellular space.
* Once outside the cell, procollagen molecules undergo further modifications, including the removal of terminal propeptides by specific enzymes called procollagen peptidases.
* These peptidases cleave the propeptides, resulting in the formation of mature collagen fibrils.

**4. Fibril Formation and Crosslinking:**
* Collagen molecules spontaneously self-assemble into fibrils, which are long, thin, and highly organized structures.
* The assembly is driven by hydrophobic interactions and hydrogen bonding between collagen molecules.
* Mature collagen fibrils are stabilized by crosslinks, covalent bonds that form between lysine and hydroxylysine residues.
* These crosslinks provide strength and resilience to collagen fibrils, contributing to their structural integrity.

**5. Degradation:**
* Collagen is constantly being synthesized and degraded, maintaining tissue homeostasis and allowing for repair and remodeling.
* Degradation is initiated by enzymes called matrix metalloproteinases (MMPs), which break down collagen fibrils into smaller fragments.
* MMPs are regulated by various factors, including cytokines, growth factors, and mechanical forces.
* Degradation products are then further processed and recycled or excreted from the body.

Collagen metabolism is a highly regulated process, and dysregulation can contribute to various diseases, including:
* **Osteogenesis imperfecta:** A genetic disorder characterized by weak bones due to mutations in collagen genes.
* **Ehlers-Danlos syndrome:** A group of inherited disorders that affect connective tissues due to mutations in collagen or related enzymes.
* **Scurvy:** A deficiency in vitamin C, which is required for collagen synthesis, leading to weakened connective tissues and impaired wound healing.
* **Cancer:** Abnormal collagen metabolism can promote tumor growth and metastasis.

Overall, collagen metabolism is essential for maintaining tissue structure, function, and repair. Understanding this complex process is crucial for developing therapies to treat diseases related to collagen dysfunction.
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Proteins (3)

Compounds (61)