Post on 01-Apr-2015
transcript
Glycolipids
By
Amr S. Moustafa, M.D.; Ph.D.
Outlines
Overview and Functions
Structure and Types
Synthesis and Degradation
Sphingolipidosis
Overview Essential component of membranes Abundant in nervous tissue Extra-nervous tissue:
e.g., Receptors forCholera toxins Diphtheria toxinsViruses
Regulation of growth & development Very antigenic:
Blood group antigenEmbryonic antigenTumor antigen
Cell transformation
OverviewCONT’D
Sphingolipids: Structure and
TypesCeramide = Sphingosine + fatty acid
Sphingomyelin = Ceramide + Phosphorylcholine
Cerebrosides = Ceramide + Monosaccharides
Gangliosides = Ceramide oligosaccharides + NANA
Globoosides = Ceramide + Oligosaccharides
Neutral Glycosphingolipids
Globosides = Ceramide Oilgosaccharides
Cerebrosides = Ceramide monosaccharides
Galactocerbrosides = Ceramide + Galactose Glucocerbrosides = Ceramide + Glucose
Lactosylceramide = Cer-Glc-GalForssman antigen = Cer-Glc-(Gal)2-(GalNac)2
Galactocerbroside
AcidicAcidic
GlycosphingolipidsNegatively charged at physiological pH
1. Gangliosides:Most complexGanglion cellsCeramide oligosaccharides + NANA
2. Sulfatides:Nerve tissue and kidneysCerbrosides + Sulfated Gal
Gangliosides
GM2
Sulfate donor: PAPS
Sulfatides
Galactocerbroside 3-sulfate
Sphingolipids’ Synthesis
Sphingolipids’ Degradation
Lysosomal hydrolytic enzymes
Last on, First off
Defective: Total or partial Sphingolipidosis
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
Sphingolipidosis
Measure enzyme activityCultured fibroblasts or peripheral leukocytesCultured amniocytes (prenatal)
Histologic examination DNA analysis
Replacement Therapy: Recombinant human enzyme
Bone marrow transplantation: Gaucher disease
Diagnosis:
Treatment:
CONT’D
Sphingolipidosis
CONT’D
Niemann - Pick Disease
Gaucher Disease
ProstaglandinsEicosanoids (20 C):
Prostaglandins (PG)Thromboxanes (TX)Leukotrienes (LT)
PG Vs Hormones:All cellsLocal acting & Not storedShort half-lifePlasma membrane & nuclear receptors
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
Prostaglandin’S Synthesis
CONT’D
COX Isoenzymes
COX-1:ConstitutiveMost tissuesImportant for:
Integrity of gastric mucosaRenal homeostasisPlatelet aggregation
COX Isoenzymes
COX-2InducibleLimited No. of tissuesStimulus:
Products of inflammatory & immune cells
Mediates:Inflammatory response:
Pain, Redness & SwellingFever of infection
CONT’D
COX Inhibitors
Cortisol (Steroid):Selective COX-2 (-)Phospholipase A2 (-)
NSAIDS:Both COX-1 and –2 (-)Side effects: Gastric, Renal & ClottingLow-dose Asprin therapy
Celecoxib: Selective COX-2 (-)
Prostaglandin’S Functions