Transcript Complex Lipids - Shifa College of Medicine

Complex Lipids
Vignette 3
• Introduction: A 3 week premature baby boy born to a diabetic
mother by cesarean section.
• Presenting complaints: Bluish discoloration of the skin and
mucus membranes (cyanosis) with apnea.
• Examination: Unusual breathing movement -- drawing back
of chest muscles with breathing. APGAR score less than 5
• Investigations: lecithin/sphingomyelin ratio of amniotic fluid
at 34th week of gestation = 1.2
• Laboratory investigations: Blood gas analysis of baby
indicates low oxygen and excess acid in the body fluids.
Blood culture negative for infection.
• Diagnosis: Acute respiratory distress syndrome (ARDS)/
Infant respiratory distress syndrome (IRDS)
Classification - (Structure)
LIPIDS
SIMPLE
LIPIDS
Fats and
Oils
Waxes
Glycerophospholipids
COMPLEX
LIPIDS
Phospholipids
Sphingophospho
lipids
Cerebrosides
Glycolipids
Globo- Gangliosides
sides
Sulfatides
GLYCEROL
Simple Lipids
FATTY ACID
FATTY ACID
FATTY ACID
Triacylglyceride
Complex lipids:
Phospholipids
Glycerophospholipids Ether Glycerolipids
Sphingophospholipids
Glycerophospholipids
Phosphatidic acid
GLYCEROL
FATTY ACID
FATTY ACID
P
Glycerophospholipids
(16:0, 18:0)
(18:1, 18:2, 18:3)
Phosphatidylcholine
Lung surfactant = 90% lipids (Dipalmitoylphosphatidylcholine, DPPC; Dipalmitoylecithin) + 10% protein
Cardiolipin
Diphosphatidylglycerol
Distribution:
Inner mitochondrial
membrane
Function:
Maintenance of
respiratory
complexes
Ether Glycerolipids
Plasmalogens
Distribution:
Phosphatidalethanolamine
(in nerve tissue)
Phosphatidalcholine (in
heart muscle)
Function:
More resistant to
oxidative stress
therefore provides
protection to tissues
with active aerobic
metabolism
Platelet-activating factor
Distribution
Released by a variety of
cell types, including
platelets, neutrophils,
basophils, and endothelial
cells.
Functions
PAF activates inflammatory
cells and mediates
hypersensitivity, acute
inflammatory, and
anaphylactic reactions.
Phosphatidylinositol (PI)
Stearic acid (18:0)
Arachidonic acid (20:4)
Distribution
present in all tissues
and cell types.
Especially abundant in
brain tissue, (10% of the
phospholipids).
Functions:
Cell signaling,
Reservoir of arachidonic
acid
Protein anchoring
Phosphatidylinositol 4, 5 –
bisphosphate (PIP2)
Protein anchoring
Sphingophospholipids
Sphingophospholipids
Sphingosine
2-amino-4-octadecene-1,3-diol
C-18 alcohol containing two –OH groups, one
amino group and one double bond
Sphingomyelin
Distribution
Constituent of the
myelin sheath of nerve
fibers.
Functions
Building block of myelin
sheath
Primary source of
ceramide
Signal transduction
Phospholipids - Degradation
Niemann-Pick disease
• autosomal recessive
disease
• inability to degrade
sphingomyelin.
• deficiency of
sphingomyelinase - a
type of phospholipase
C.
Glycolipids/glycosphingolipids
SPHING
Glycolipids/glycosphingolipids
SINE
FATTY ACID
CARBOHYDRATE
Glycolipids/glycosphingolipids
CEREBROSIDES
GLOBOSIDES
GANGLIOSIDES
SULFATIDES
Distribution
essential components of all
membranes in the body.
greatest amounts in nerve
tissue
Functions
regulation of cellular
interactions, growth, and
development
Blood group antigens
Cerebrosides
• ceramide monosaccharides -simplest neutral
glycosphingolipids
• Galactocerebroside - the most common
cerebroside found in membranes
• Glucocerebroside - serves primarily as an
intermediate in the synthesis and degradation of the
more complex glycosphingolipids.
• cerebrosides are found predominantly in the brain
and peripheral nervous tissue, with high
concentrations in the myelin sheath
Galactocerebroside
Globosides
• Ceramide oligosaccharides
• Addition of monosaccharides (including
GalNAc) to a glucocerebroside
e.g.
Cer-Glc-Gal (lactosylceramide)
Cer-Glc-Gal-Gal-GalNac-GalNac
(Forssman antigen)
Gangliosides
• Negatively charged at
physiological pH
• Glycolipids containing sialic
acid (N-acetylneuraminic
acid, NANA)
• found primarily in the
ganglion cells of the central
nervous system, particularly
at the nerve endings
Gangliosides
Nomenclature
• is based on the number of sialic acid residues
– 'GM' a single (mono) sialic acid,
– GD, GT and GQ two, three and four sialic acid
residues in the molecule, respectively
• on the sequence of the carbohydrates.
– The number after the GM, e.g. GM1 refers to
the structure of the oligosaccharide.
– These numbers were derived from the relative
mobility of the glycolipids on thin layer
chromatograms; the larger, GM1,
gangliosides migrate the most slowly.
Sulfatides
• cerebrosides that contain
sulfated galactosyl
residues
• negatively charged at
physiologic pH
• found predominantly in
nerve tissue and kidney
Sphingolipidosis
• Defects in sequential degradation of glycolipids
lead to a number of lysosomal storage diseases,
Sphingolipidosis (cerebrosidoses and
gangliosidoses)
• A specific lysosomal hydrolytic enzyme is deficient
in each disorder. Therefore, usually only a single
sphingolipid (the substrate for the deficient
enzyme) accumulates in the involved organs in
each disease
THE END!