Mucopolysaccharides
Feature | Proteoglycans / GAG | Glycoproteins |
Oligosaccharide Chains | Long, unbranched GAG chains | Short, highly branched oligosaccharide chains |
Components | Amino sugars and uronic acid (except Keratan sulfate) | Amino sugars, no uronic acid |
Structure and Charge | Heavily glycosylated, negatively charged → Can hold water | ㅤ |
Disaccharide Unit | Repeating disaccharide unit (amino sugar + uronic acid) | ㅤ |
Examples | Aggrecans, Syndecans, Chondroitin sulphate, Keratan sulphate, Dermatan sulphate, Heparan sulphate, Heparin, Hyaluronic acid | Collagen, Mucin |
Site/Location | Connective tissue & Extracellular Matrix (ECM); Heparin intracellularly | Cell surface and secretory proteins |
Glycoprotein
Function | Glycoproteins |
Structural component | Collagens |
Lubricant and protective | Mucins |
Transport | Transferrin, ceruloplasmin |
Immunologic | Immunoglobulins, Histocompatibility antigens |
Hormone | Chorionic gonadotropin, TSH |
Enzyme | Alkaline phosphatase |
Antifreeze | Plasma proteins of cold-water fish |
Interact with specific carbohydrates | Lectins, selectins |
Regulate folding of proteins | Calnexin, calreticulin |
Developmental Regulation | NOTCH → T ALL |
Proteoglycan / GAG
- They are long, straight, unbranched chains.
- Normal structure: N Acetyl Glucosamine + Glucuronic acid
Glycosaminoglycans/Proteoglycan | Disaccharide Repeat Units |
Keratan sulfate | • N Acetyl Glucosamine + Galactose • Galactose instead of uronic acid. |
Hyaluronic acid | • N Acetyl Glucosamine + Glucuronic acid |
Chondroitin sulfate | • N Acetyl Galactosamine + Glucuronic acid |
Dermatan sulfate | • N Acetyl Galactosamine + Iduronic acid |
Heparan sulfate | • N Acetyl Glucosamine + Glucuronic acid |
Heparin | • N Sulfated Glucosamine + Iduronic acid |
Components:
- Contain repetitive, alternating units
- Uronic acid,
- Glucuronic acid.
- Amino sugar,
- Glucosamine
- Sulphate.
- Dermatil Harapin Idu (Iduronic acid)
- If “d” in name → N acetyl galactosamine
- D→ Diii → GIrl → Gal
- Rest N Acetyl Glucosamine
- Only one with no uronic acid → Keratan sulfate → Galactose instead
Location
Mucopolysaccharide | Location(s) | Roles |
Hyaluronic acid | • Synovium, Vitreous | • Cell migration, wound repair, Morphogenesis • No protein linkage • No sulphate |
Keratan sulfate type 1 | • Cornea | • Maintain corneal transparency |
Keratan sulfate type 2 | • Cartilage (Loose connective tissue) • Keratan → Ka Ka → Cornea, Cartilage | ㅤ |
Heparin | • Mast cells | • Only intracellular GAG (natural anticoagulant) • Used for the estimation of LPL in ↳ type 1 hyperlipoproteinemia |
Heparan sulfate | • Glomerular basement membrane • Aortic wall | • Negative charge of the GBM • Holds Lipoprotein Lipase to vascular endothelium |
Chondroitin sulfate | • Cartilage, Bone | • Most abundant GAG. • Enables compressibility of cartilage. |
Dermatan sulfate | • Skin, Sclera • ECM of all tissues (widest distribution) | • Atherogenic GAG (attracts LDL) • Maintains structure of sclera |
NOTE:
- NANA (N-acetylneuraminic acid) is not a component.
- It is a component of glycolipid (specifically ganglioside).
Mucopolysaccharidosis (MPS)
Type | Name | Enzyme Deficiency | ㅤ |
1 | Hurler | α-L-Iduronidase | • Visual disturbances + • Mental retardation |
1 | Scheie | α-L-Iduronidase (Partial defect) | • Hirsutism • Normal intelligence |
2 | Hunter | Iduronate sulfatase | • X linked, • No corneal clouding • Intellectual disability • Aggressive behavior I du(Iduronate sulfatase) wanna hunt |
3 | Sanfilippo | Heparin-S-sulfamidase (degrades heparan sulfate) | • M/c MPS • No corneal clouding • Behavioral problems prominent |
4 | Morquio disease | Galactosamine-6-sulphatase, β-galactosidase | • Severe skeletal dysplasia • Normal Intelligence • No Visceromegaly • No Reilly body inclusion More Que → caused Skeletal problem → give β guy some milk (β galactosidase) |
6 | Maroteaux-Lamy | Aryl sulfatase B | • Similar to MPS I • Normal intelligence |
9 | Natowicz syndrome | Hyaluronidase | _ |
Mnemonic:
- All present → Hurler
- Normal intelligence
- Mo () Mo () shie ()
- She → No MR → But Hirsuitism → DS
- Ass → Idurunidase
- Martolamy → Like She → No MR, No Hirsuitism → DS
- Mola (Morattu Lamy) → Arya Stark (Aryl sulfatase)
- Has Nagam (Nagalzyme) around her
- More Que →Four Que
- No visceromegaly
- Only 1 without Visceromegaly
- No Leucocyte inclusions
- Only 1 without Leucocyte inclusions
- Clear vision
- Hunters and Filippines (San filippo) are similar
- Hunters
- aggressively (Aggressive behavious)
- aim for the X (X-linked recessive).
- Hunter ate → Iduronate
- Pebbly skin
- Filippines
- more common
- But not a common answer
- Hydrops fetalis only in
- Sly
Indication | Name | ERT Drug | GAG Type | Rx/Mnemonic |
MPS I - H | Hurler | Aldurazyme (laronidase) | DS + HS | • Stem Cell therapy • Substate Reduction Therapy (Flavinoids) |
MPS I - S | Scheie | Aldurazyme (laronidase) | DS | • 1st → Aldurantham |
MPS 2 | Hunter | Elaprase (idursulfase) | DS + HS | • Best hunterkk Praise kodukkum • (Elaprase) |
MPS 6 | Maroteaux-Lamy | Naglazyme (galsulfase) | DS | • Arya Stark (Aryl sulfatase) • Has Nagam (Nagalzyme) around her |
- HHHH → Hunter, Hurler, Heparan sulphate
Confirmatory Tests
- Enzyme Activity Assay
- In leukocytes or fibroblasts
- Genetic tests
Prenatal Diagnosis
- Amniocentesis/CVS
- For enzyme assay or gene testing
Inheritance:
- All AR
- except Hunter (X-linked)
- Fabry Mnemonic: X-linked
Clinical of Hurler:
- Coarse facies, hepatosplenomegaly
- puffy-looking facies,
- periorbital puffiness,
- depressed nose bridge,
- prominent philtrum,
- protruding tongue
- Intellectual disability/mental retardation
- Dysostosis multiplex
- Thickened skull
- J-shaped sella
- Paddle ribs
- Bullet phalanges
- Vertebral beaking
- Corneal clouding
- Cardiac issues,
- Airway obstruction
Aryl suphatase
- Metachromatic leukodystrophy
- Enzyme: Arylsulfatase A
- CNS involvement present
- Maroteaux-Lamy
- Enzyme: Arylsulfatase B
- No CNS involvement
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