Glycolipids

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Glycolipids
By
Amr S. Moustafa, M.D. Ph.D.
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Outlines
Overview and Functions Structure and
Types Synthesis and Degradation Sphingolipidosis
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Overview

• Essential component of membranes
• Abundant in nervous tissue
• Extra-nervous tissue
• e.g., Receptors for
• Cholera toxins
• Diphtheria toxins
• Viruses

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Overview
CONTD

• Regulation of growth development
• Very antigenic
• Blood group antigen
• Embryonic antigen
• Tumor antigen
• Cell transformation

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Sphingolipids Structure and Types
Ceramide Sphingosine fatty acid
Sphingomyelin Ceramide Phosphorylcholine
Cerebrosides Ceramide Monosaccharides
Globoosides Ceramide Oligosaccharides
Gangliosides Ceramide oligosaccharides NANA
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Neutral Glycosphingolipids
Cerebrosides Ceramide monosaccharides
Galactocerbrosides Ceramide Galactose
Glucocerbrosides Ceramide Glucose
Globosides Ceramide Oilgosaccharides
Lactosylceramide Cer-Glc-Gal Forssman antigen
Cer-Glc-(Gal)2-(GalNac)2
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Galactocerbroside
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Acidic
Acidic Glycosphingolipids
Negatively charged at physiological pH

• Gangliosides
• Most complex
• Ganglion cells
• Ceramide oligosaccharides NANA

2. Sulfatides Nerve tissue and
kidneys Cerbrosides Sulfated Gal
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Gangliosides
GM2
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Sulfate donor PAPS
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Sulfatides
Galactocerbroside 3-sulfate
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Sphingolipids Synthesis
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Sphingolipids Degradation
Lysosomal hydrolytic enzymes Last on, First
off Defective Total or partial
Sphingolipidosis
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Sphingolipidosis

• Synthesis (Normal) Degradation (Defective)
• Substrate accumulates in organs
• Progressive, early death
• Phenotypic and genotypic variability
• Autosomal recessive, Except Fabry (X-linked)
• Rare, Except Ashkenazi Jewish

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Sphingolipidosis
CONTD
Diagnosis

• Measure enzyme activity
• Cultured fibroblasts or peripheral leukocytes
• Cultured amniocytes (prenatal)
• Histologic examination
• DNA analysis

Treatment

• Replacement Therapy
• Recombinant human enzyme
• Bone marrow transplantation Gaucher disease

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Sphingolipidosis
CONTD
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Niemann - Pick Disease
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Gaucher Disease
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Prostaglandins
Eicosanoids (20 C) Prostaglandins
(PG) Thromboxanes (TX) Leukotrienes (LT)
PG Vs Hormones All cells Local acting Not
stored Short half-life Plasma membrane
nuclear receptors
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ProstaglandinS Synthesis
Dietary precursor Linoleic acid 182 (9, 12)
Immediate precursor Arachidonic acid 204 (5,
8,11,14)
Prostaglandin endoperoxide synthase Microsomal
enzyme Two Catalytic activities Fatty acid
cyclooxygenase (COX), 2 O2 Peroxidase (GSH)
Parent Prostaglandin PGH2
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ProstaglandinS Synthesis
CONTD
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COX Isoenzymes
COX-1 Constitutive Most tissues Important
for Integrity of gastric mucosa Renal
homeostasis Platelet aggregation
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COX Isoenzymes
CONTD
COX-2 Inducible Limited No. of
tissues Stimulus Products of inflammatory
immune cells Mediates Inflammatory
response Pain, Redness Swelling Fever of
infection
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COX Inhibitors
Cortisol (Steroid) Selective COX-2
(-) Phospholipase A2 (-)
NSAIDS Both COX-1 and 2 (-) Side effects
Gastric, Renal Clotting Low-dose Asprin therapy
Celecoxib Selective COX-2 (-)
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ProstaglandinS Functions