Glycosaminoglycans,proteoglycans&glycoproteinsDENS

Overview:
- Structure: Long, unbranched heteropolysaccharide chains composed of repeating disaccharide units (acidic sugar + amino sugar).
- Function: Provide structural support, hydration, and lubrication in the extracellular matrix (ECM). They act as molecular sieves, influencing the movement of materials through the ECM.
- Location: Found in connective tissues, cartilage, synovial fluid, and other extracellular spaces.
Classification:
- Chondroitin Sulfate: Most abundant; found in cartilage, tendons, and ligaments.
- Keratan Sulfate: Found in the cornea and loose connective tissue.
- Hyaluronic Acid: Acts as a lubricant and shock absorber in synovial fluid and the vitreous humor of the eye.
- Dermatan Sulfate: Contributes to skin elasticity and resilience.
- Heparin: Acts as an anticoagulant; found in mast cells.
- Heparan Sulfate: Plays a role in cell signaling and interactions with growth factors.
Synthesis:
- GAGs are synthesized in the Golgi apparatus by sequential addition of acidic and amino sugars from UDP-derivatives.
- Sulfation occurs after monosaccharides are incorporated into the growing GAG chain.
Degradation:
- GAGs are degraded in lysosomes by acid hydrolases. Deficiencies in these enzymes lead to mucopolysaccharidoses (MPS), a group of hereditary diseases characterized by the accumulation of partially degraded GAGs.

Overview:
- Structure: GAGs covalently attached to a core protein, forming a "bottle brush" structure.
- Function: Provide structural integrity to the ECM, act as signaling molecules, and regulate cell behavior.
Proteoglycan Monomers:
- GAGs (except hyaluronic acid) are attached to core proteins via a trihexoside linker (galactose-galactose-xylose) bound to a serine residue.
Proteoglycan Aggregates:
- Proteoglycan monomers associate with hyaluronic acid to form large aggregates, stabilized by link proteins.
Synthesis:
- Core proteins are synthesized in the rough endoplasmic reticulum (RER) and glycosylated in the Golgi apparatus.
- GAG chains are elongated by glycosyltransferases, and sulfate groups are added post-translationally.

Overview:
- Structure: Proteins with short, branched oligosaccharide chains attached via N-glycosidic (asparagine) or O-glycosidic (serine/threonine) linkages.
- Function: Involved in cell surface recognition, antigenicity, and as protective biologic lubricants.
Synthesis:
- Glycoproteins are synthesized in the RER and Golgi apparatus.
- N-linked glycoproteins: Oligosaccharides are synthesized on dolichol pyrophosphate and transferred to asparagine residues.
- O-linked glycoproteins: Oligosaccharides are added directly to serine or threonine residues.
Degradation:
- Glycoproteins are degraded in lysosomes by acid hydrolases. Deficiencies in these enzymes lead to oligosaccharidoses, rare genetic diseases characterized by the accumulation of partially degraded glycoproteins.

Mucopolysaccharidoses (MPS):
- Hereditary diseases caused by deficiencies in lysosomal enzymes that degrade GAGs.
- Examples: Hurler syndrome (α-L-iduronidase deficiency), Hunter syndrome (iduronate sulfatase deficiency), Sanfilippo syndrome (heparan sulfate degradation defects).
- Symptoms: Skeletal abnormalities, mental retardation, and early death.
- Treatment: Enzyme replacement therapy and bone marrow transplantation.
I-Cell Disease:
- A rare lysosomal storage disorder caused by the inability to phosphorylate mannose residues, leading to incorrect targeting of lysosomal enzymes.
- Symptoms: Skeletal abnormalities, restricted joint movement, and severe psychomotor impairment.
Oligosaccharidoses:
- Rare genetic diseases caused by deficiencies in glycoprotein degradation enzymes.
- Example: α-Mannosidosis (α-mannosidase deficiency), leading to the accumulation of mannose-rich oligosaccharides.