Complex LipidsComplex Lipids

• 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)

Vignette 3Vignette 3

LIPIDS

SIMPLELIPIDS

COMPLEXLIPIDS

ClassificationClassification - (Structure) - (Structure)

Fats and Fats and Oils Oils

WaxesWaxes PhospholipidsPhospholipids GlycolipidsGlycolipids

Glycero-Glycero-phospho-phospho-lipidslipids

Sphingo-Sphingo-phosphophospholipidslipids

Cerebro-Cerebro-sidessides

Globo-Globo-sidessides

Ganglio-Ganglio-sidessides

Sulfa-Sulfa-tidestides

Simple LipidsSimple Lipids

Triacylglyceride

FATTY ACID

FATTY ACID

FATTY ACID

Complex lipids: Complex lipids: PhospholipidsPhospholipids

GlycerophospholipidsGlycerophospholipids Ether Glycerolipids Sphingophospholipids

GlycerophospholipidsGlycerophospholipids

Phosphatidic acidPhosphatidic acid

FATTY ACID

FATTY ACID

PP

GlycerophospholipidsGlycerophospholipids

(16:0, 18:0)

(18:1, 18:2, 18:3)

PhosphatidylcholinePhosphatidylcholineLung surfactant = 90% lipids (Dipalmitoylphosphatidyl-choline, DPPC; Dipalmitoylecithin) + 10% protein

CardiolipinCardiolipin

DistributionDistribution::

Inner mitochondrial Inner mitochondrial membranemembrane

FunctionFunction::

Maintenance of Maintenance of respiratory respiratory complexescomplexes

Diphosphatidylglycerol

Ether GlycerolipidsEther Glycerolipids

PlasmalogensPlasmalogens

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 factorPlatelet-activating factor

DistributionReleased by a variety of cell types, including platelets, neutrophils, basophils, and endothelial cells.FunctionsPAF activates inflammatory cells and mediates hypersensitivity, acute inflammatory, and anaphylactic reactions.

Phosphatidylinositol (PI)Phosphatidylinositol (PI)

Distributionpresent in all tissues and cell types. Especially abundant in brain tissue, (10% of the phospholipids).

Functions:Cell signaling,Reservoir of arachidonic acidProtein anchoring

Stearic acid (18:0)

Arachidonic acid (20:4)

Phosphatidylinositol 4, 5 –Phosphatidylinositol 4, 5 –bisphosphate (PIP2)bisphosphate (PIP2)

Protein anchoringProtein anchoring

SphingophospholipidsSphingophospholipids

SphingophospholipidsSphingophospholipids

SphingosineSphingosine

2-amino-4-octadecene-1,3-diolC-18 alcohol containing two –OH groups, one amino group and one double bond

SphingomyelinSphingomyelin

DistributionConstituent of the myelin sheath of nerve fibers.FunctionsBuilding block of myelin sheathPrimary source of ceramideSignal transduction

Phospholipids - Phospholipids - DegradationDegradation

Niemann-Pick diseaseNiemann-Pick disease

• autosomal recessive disease

• inability to degrade sphingomyelin.

• deficiency of sphingomyelinase - a type of phospholipase C.

Glycolipids/Glycolipids/glycosphingolipidsglycosphingolipids

FATTY ACID

O SINE

CARBOHYDRATE

Glycolipids/Glycolipids/glycosphingolipidsglycosphingolipids

Glycolipids/Glycolipids/glycosphingolipidsglycosphingolipids

Distributionessential components of all membranes in the body. greatest amounts in nerve tissue

Functionsregulation of cellular interactions, growth, and developmentBlood group antigens

CEREBROSIDES

GLOBOSIDES

GANGLIOSIDES

SULFATIDES

CerebrosidesCerebrosides

• 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

GalactocerebrosideGalactocerebroside

GlobosidesGlobosides

• Ceramide oligosaccharides

• Addition of monosaccharides (including GalNAc) to a glucocerebroside

e.g.

Cer-Glc-Gal (lactosylceramide)

Cer-Glc-Gal-Gal-GalNac-GalNac (Forssman antigen)

• 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

GangliosidesGangliosides

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.

GangliosidesGangliosides

• cerebrosides that contain sulfated galactosyl residues

• negatively charged at physiologic pH

• found predominantly in nerve tissue and kidney

SulfatidesSulfatides

• 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

SphingolipidosisSphingolipidosis

THE END!THE END!