proteoglycan metabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways involving proteoglycans, any glycoprotein in which the carbohydrate units are glycosaminoglycans. [GOC:mah, ISBN:0198506732]

Proteoglycan metabolism is a complex and dynamic process that involves the synthesis, modification, assembly, and degradation of proteoglycans, which are macromolecules composed of a core protein attached to one or more glycosaminoglycan (GAG) chains. These molecules play crucial roles in various biological processes, including cell signaling, cell adhesion, tissue morphogenesis, and extracellular matrix (ECM) organization.

**1. Synthesis:**

- **Core Protein Synthesis:** The core protein, the protein backbone of a proteoglycan, is synthesized on ribosomes and transported to the endoplasmic reticulum (ER), where it undergoes initial modifications, such as glycosylation.
- **GAG Synthesis:** GAGs are long, unbranched polysaccharide chains composed of repeating disaccharide units. They are synthesized in the Golgi apparatus, where specific enzymes attach sugar residues to the core protein.
- **GAG Modification:** After synthesis, GAG chains undergo further modifications, such as sulfation and epimerization, which influence their structure and function.

**2. Assembly:**

- **GAG Attachment:** The synthesized GAG chains are attached to the core protein, usually in the Golgi apparatus, to form the complete proteoglycan molecule.
- **Self-Assembly:** Proteoglycans can interact with each other and with other ECM components, such as collagen and elastin, forming complex structures that provide support and organization to tissues.

**3. Function:**

- **Cell Signaling:** Proteoglycans can bind to growth factors, cytokines, and other signaling molecules, influencing their activity and availability.
- **Cell Adhesion:** They can act as adhesion molecules, mediating cell-cell and cell-ECM interactions.
- **ECM Organization:** Proteoglycans play a critical role in the structural integrity and organization of the ECM, providing hydration, tensile strength, and flexibility.

**4. Degradation:**

- **Enzymatic Degradation:** Proteoglycans are degraded by specific enzymes called proteoglycanases and glycosidases, which cleave the core protein and GAG chains, respectively.
- **Lysosomal Degradation:** Degraded proteoglycans are taken up by cells through endocytosis and delivered to lysosomes for further breakdown.

**5. Regulation:**

- **Gene Expression:** The expression of proteoglycan genes is tightly regulated by various factors, including growth factors, hormones, and cytokines.
- **Post-Translational Modifications:** The modification of proteoglycans, such as sulfation and epimerization, is also regulated, influencing their functional properties.

**Disruption of proteoglycan metabolism is linked to various diseases, including:**

- **Arthritis:** Altered proteoglycan composition and degradation contribute to cartilage breakdown in osteoarthritis.
- **Cancer:** Proteoglycans can promote tumor growth and metastasis by providing a favorable microenvironment for cancer cells.
- **Developmental Disorders:** Mutations in genes involved in proteoglycan biosynthesis can lead to skeletal and connective tissue defects.

**Overall, proteoglycan metabolism is a fundamental process that plays a vital role in maintaining tissue homeostasis, cell signaling, and developmental processes. Understanding this intricate pathway is essential for unraveling the pathogenesis of various diseases and for developing targeted therapeutic strategies.'
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Proteins (1)

Compounds (10)