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Metabolism of Acylglycerols
& Sphingolipids
BIOMEDICAL IMPORTANCE
• Acylglycerols constitute the majority of lipids in the
body.
• Obesity, diabetes,and hyperlipoproteinemia
• Cell membranes
• Lung surfactant
• Hormone second messengers
• Platelet-activating factor
• cell adhesion and cell recognition
• as receptors for bacterial toxins
• ABO blood group substances
• Glycolipid storage diseases
TRIACYLGLYCEROLS
• HYDROLYSIS INITIATES CATABOLISM OF
TRIACYLGLYCEROLS
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Lipolysis (Lipase)
adipose tissue
free fatty acids
Serum albumin
Uptake into tissues
• Oxidized or reesterified
– Glycerol
• Glycerol kinase
Overview of acylglycerol biosynthesis
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Phosphatidate Is the Common Precursor
Both glycerol & fatty acids must be activated
Glycerol 3-phosphate
Activation of fatty acids
– acyl-CoA synthetase
• Acyltransferase
• Most of the activity of these enzymes resides in
the endoplasmic reticulum of the cell, but some
is found in mitochondria
• Choline or ethanolamine must first be
activated
• Cardiolipin
Biosynthesis of cardiolipin
GLYCEROL ETHER PHOSPHOLIPIDS
• BIOSYNTHESIS
– in peroxisomes
• Plasmalogens
– 1-alkyl-2-acylglycerol 3-phosphoethanolamine
• Plateletactivating factor (PAF)
– 1-alkyl-2-acetyl-sn-glycerol-3- phosphocholine
• Involved in
– Inflammation, chemotaxis, and protein
phosphorylation.
Biosynthesis of ether lipids
Biosynthesis of ether lipids
• Phospholipases
– allow degradation & remodeling of
phosphoglycerols
Metabolism of phosphatidylcholine
(lecithin)
Sites of the hydrolytic activity of phospholipases
• Long-chain saturated fatty acids are found
predominantly in the 1 position of phospholipids
• the polyunsaturated acids (eg, the precursors of
prostaglandins) are incorporated more into the 2
position
• The incorporation of fatty acids into lecithin; by,
– Complete synthesis of the phospholipid
– Transacylation between cholesteryl ester and
lysolecithin
– Direct acylation of lysolecithin by acyl-CoA
SPHINGOLIPIDS
• Formed from CERAMIDE
Biosynthesis of ceramide.
Biosynthesis of sphingomyelin
Glycosphingolipids
• Simple
– Cerebrosides
• Galactosylceramide (GalCer)
• Glucosylceramide (GlcCer)
• Complex
– Gangliosides
• Contain a sialic acid, usually Nacetylneuraminic acid
• activated sugars
– Glycosyl transferases,Golgi apparatus
• active sulfate
Biosynthesis of galactosylceramide and its sulfo derivative.
(PAPS,“active sulfate,” adenosine 3′-phosphate-5′-phosphosulfate.)
Glycosphingolipids
• Constituents of the outer leaflet of plasma
membranes
– Cell adhesion and cell recognition
– Antigens
– Receptors
Biosynthesis of gangliosides
CLINICAL ASPECTS
• Respiratory Distress Syndrome
– Dipalmitoylphosphatidylcholine
• Multiple Sclerosis
– a demyelinating disease
• Loss of both phospholipids (particularly ethanolamine
plasmalogen) and of sphingolipids from white matter
• Lipidoses
– Sphingolipidoses (lipid storage diseases)
– a Lysosomal disorder
CLINICAL ASPECTS
• Features
– Complex lipids containing ceramide accumulate in
cells, particularly neurons
• The rate of synthesis of the stored lipid is
normal
• The enzymatic defect is in the lysosomal
degradation pathway
Examples of sphingolipidoses
SUMMARY
• Triacylglycerols
– The major energy-storing lipids
• Phosphoglycerols, sphingomyelin, and
glycosphingolipids
– Amphipathic
• Have structural functions in cell membranes
– Specialized roles
• Triacylglycerols and some phosphoglycerols
are synthesized by progressive acylation of
glycerol 3-phosphate.
• ether phospholipids
– Plasmalogens and platelet-activating factor (PAF)
– Formed from dihydroxyacetone phosphate
• Sphingolipids
– formed from ceramide (N-acylsphingosine)
• Gangliosides
– Complex glycosphingolipids
• Containing more sugar residues plus sialic acid
• Disease processes
– Phospholipids and sphingolipids
• Respiratory distress syndrome (lack of lung surfactant)
• Multiple sclerosis
• Sphingolipidoses