1. بسم الله الرحمن الرحيم

2. Glycolipids By
Amr S. Moustafa, M.D.; Ph.D.

3. Outlines Overview and Functions Structure and Types
Synthesis and Degradation
Sphingolipidosis

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

5. Overview Regulation of growth & development Very antigenic:
CONT’D
Regulation of growth & development
Very antigenic:
Blood group antigen
Embryonic antigen
Tumor antigen
Cell transformation

6. Sphingolipids: Structure and Types
Ceramide = Sphingosine + fatty acid
Sphingomyelin = Ceramide + Phosphorylcholine
Cerebrosides = Ceramide + Monosaccharides
Globoosides = Ceramide + Oligosaccharides
Gangliosides = Ceramide oligosaccharides + NANA

7. 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

8. Galactocerbroside

9. Acidic Glycosphingolipids
Negatively charged at physiological pH
Gangliosides:
Most complex
Ganglion cells
Ceramide oligosaccharides + NANA
2. Sulfatides:
Nerve tissue and kidneys
Cerbrosides + Sulfated Gal

10. Gangliosides
GM2

11. Sulfate donor: PAPS

12. Sulfatides
Galactocerbroside 3-sulfate

13. Sphingolipids’ Synthesis

14. Sphingolipids’ Degradation
Lysosomal hydrolytic enzymes
Last on, First off
Defective: Total or partial
Sphingolipidosis

15. 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

16. Sphingolipidosis Diagnosis: Treatment: CONT’D 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

17. CONT’D
Sphingolipidosis

18. Niemann - Pick Disease

19. Gaucher Disease

20. 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

21. Prostaglandin’S Synthesis
Dietary precursor: Linoleic acid 18:2 (9, 12)
Immediate precursor: Arachidonic acid 20:4 (5, 8,11,14)
Prostaglandin endoperoxide synthase:
Microsomal enzyme
Two Catalytic activities:
Fatty acid cyclooxygenase (COX), 2 O2
Peroxidase (GSH)
Parent Prostaglandin : PGH2

22. Prostaglandin’S Synthesis
CONT’D

23. COX Isoenzymes COX-1: Constitutive Most tissues Important for:
Integrity of gastric mucosa
Renal homeostasis
Platelet aggregation

24. COX Isoenzymes CONT’D COX-2 Inducible Limited No. of tissues Stimulus:
Products of inflammatory & immune cells
Mediates:
Inflammatory response:
Pain, Redness & Swelling
Fever of infection

25. 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 (-)

26. Prostaglandin’S Functions