Glycosphingolipids (GSLs) Flashcards
Glycosphingolipids (GSLs)
Glycogonjugates that are major parts of biological membranes
Each contain a hydrophilic sugar chain linked to a hydrophobic ceramide
The ceramide anchors it to the membrane
Act as signaling molecules to regulate differentiation, proliferation, and apoptosis
Neutral and acidic
Ceramides
Hydrophobic sugar chain in the GSLs
= a sphigosine backbone acylated by a FA
In skin, act as a water permeability barrier
Gangliosides
Major acidic acidic GSLs
= sialic acid-containing GSLs
Galactosylceramide (-cerebroside)
Neutral GSL
Galactose beta linked to ceramide
Found mainly in CNS
Associated with Krabbe Disease
Glucosylceramide (-cerebroside)
neutral GSL
Glucose beta linked to ceramide
Found in visceral organs
Associated with Gaucher disease
Lactosylceramide
GalB1–>4GlcB—>Cer
Notice: glycolipid = lactose
Neutral
Globotriaosylceramide (Gb3)
GalA1–>5GalB1–>4GlcB—>Cer
**adding another Galactose to lactosylceramide
Found in visceral organs
Associated with Fabry Disease
Neutral
Globotetraosylceramide (Gb4)
GalNAcB1–>3GalA1–>4GalB1–>4GlcB—>Cer
**adding GalNAc to Gb3
Visceral organs
Neutral
Catabolism of Gb4
Terminal B-linked GalNAc is removed —> yields Gb3
Beta-hexosaminidase A and B
Blocked in Type O Tay Sachs
Beta-hexosaminidase A & B (HexA and HexB)
both can cleave both beta linked GlcNAc and GalNAc structures
Hex A = 1 alpha and 1 beta
Hex B = 2 betas
Catabolism of Gb3
A1,4 terminal galactose is removed
Enzyme: alpha-galactosidase A
PRODUCT: lactosylceramide
Associated with Fabry Disease
Catabolism of lactosylceramide
Terminal beta1,4 galactose removed
ENZYME: beta-galactosidase
PRODUCT: glucosylceramide
Catabolism of glucosylceramide (GlcCer)
ENZYME: beta-glucosidase
PRODUCT(S): glucose and ceramide
Associated with Gaucher Disease
Catabolism of galactosylceramide (GalCer)
ENZYME: galactocerebrosidase (a beta-galactosidase)
PRODUCTS: galactose and ceramide
Associated with Krabbe disease
What sialic acid do gangliosides contain (acidic GSLs)
N-acettylneuraminic Acid (NeuAc)
The 3 acidic GSLs (gangliosides)
GM3 = shortest sugar chain
GM2
GM1
GM3
NeuAc attached to the terminal Gal of the neutral GSL (lactosylceramide)
Major ganglioside in visceral organs
GM2
Attaching an GalNAc to the galactose of the GM3
Beta-1,4
Associated with Tay-Sachs Disease
GM1
Attaching Gal to the termainl GalNAc of the GM2
Beta-1,3 linkage
Major ganglioside of the CNS
Receptor of the cholera toxin
Nomenclature of gangliosides
GM#
G = ‘ganglioside’
M# = number of sugar cahins (5-n)
—> n= number of sugar units in the main chain
Ex: GM1 because it has 4 sugars in the chain
Catabolism of GM1
Terminal Galactose (beta1,3)
Enzyme: beta-galactosidase
Associated with GM1-gangliosidosis (or generalized gangliosidosis)
Catabolism of GM2
Terminal GalNAc is hydrolyzed (B1,4)
Enzyme: beta-hexoaminidase A (Hex A)
co-factor: GM2-activator
…now have GM3
Associated with Tay Sachs
Catabolism of GM3
terminal NeuAc (alpha2,3)
Enzyme: sialidase (neuraminidase)
…now have lactosylceramide…wich can be converted to glucosylceramide with a beta-galactosidase
Basic unit of the all antigens on RBCs
GalB1–>4GlcNAcB1–>RBC
