Page last updated: 2024-10-24

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)

ProteinDefinitionTaxonomy
HeparanaseA heparanase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y251]Homo sapiens (human)

Compounds (10)

CompoundDefinitionClassesRoles
astemizoleastemizole : A piperidine compound having a 2-(4-methoxyphenyl)ethyl group at the 1-position and an N-[(4-fluorobenzyl)benzimidazol-2-yl]amino group at the 4-position.

Astemizole: Antihistamine drug now withdrawn from the market in many countries because of rare but potentially fatal side effects.
benzimidazoles;
piperidines
anti-allergic agent;
anticoronaviral agent;
H1-receptor antagonist
cisapridecisapride : The amide resulting from formal condensation of 4-amino-5-chloro-2-methoxybenzoic acid with cis-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-amine. It has been used (as its monohydrate or as its tartrate) for the treatment of gastro-oesophageal reflux disease and for non-ulcer dyspepsia, but its propensity to cause cardiac arrhythmias resulted in its complete withdrawal from many countries, including the U.K., and restrictions on its use elsewhere.

Cisapride: A substituted benzamide used for its prokinetic properties. It is used in the management of gastroesophageal reflux disease, functional dyspepsia, and other disorders associated with impaired gastrointestinal motility. (Martindale The Extra Pharmacopoeia, 31st ed)
benzamides
labetalol2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide : A member of the class of benzamides that is benzamide substituted by a hydroxy group at position 2 and by a 1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl group at position 5.

labetalol : A diastereoisomeric mixture of approximately equal amounts of all four possible stereoisomers ((R,S)-labetolol, (S,R)-labetolol, (S,S)-labetalol and (R,R)-labetalol). It is an adrenergic antagonist used to treat high blood pressure.

Labetalol: A salicylamide derivative that is a non-cardioselective blocker of BETA-ADRENERGIC RECEPTORS and ALPHA-1 ADRENERGIC RECEPTORS.
benzamides;
benzenes;
phenols;
primary carboxamide;
salicylamides;
secondary alcohol;
secondary amino compound
hesperidinhesperidin : A disaccharide derivative that consists of hesperetin substituted by a 6-O-(alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl moiety at position 7 via a glycosidic linkage.

Hesperidin: A flavanone glycoside found in CITRUS fruit peels.
3'-hydroxyflavanones;
4'-methoxyflavanones;
dihydroxyflavanone;
disaccharide derivative;
flavanone glycoside;
monomethoxyflavanone;
rutinoside
mutagen
metergolinemetergoline : An ergoline alkaloid that is the N-benzyloxycarbonyl derivative of lysergamine. A 5-HT2 antagonist. Also 5-HT1 antagonist and 5-HT1D ligand. Has moderate affinity for 5-HT6 and high affinity for 5-HT7.

Metergoline: A dopamine agonist and serotonin antagonist. It has been used similarly to BROMOCRIPTINE as a dopamine agonist and also for MIGRAINE DISORDERS therapy.
carbamate ester;
ergoline alkaloid
dopamine agonist;
geroprotector;
serotonergic antagonist
naringin(2S)-flavan-4-one;
4'-hydroxyflavanones;
dihydroxyflavanone;
disaccharide derivative;
neohesperidoside
anti-inflammatory agent;
antineoplastic agent;
metabolite
amodiaquine hydrochloride
phosphomannopentaose sulfatephosphomannopentaose sulfate: structure in first source
rk 682
pg 545PG 545: an anti-angiogenesis agent with heparanase inhibitory activity; structure in first source