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Metabolism of Acylglycerols & Sphingolipids

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Presentation on theme: "Metabolism of Acylglycerols & Sphingolipids"— Presentation transcript:

1 Metabolism of Acylglycerols & Sphingolipids

2 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

3 TRIACYLGLYCEROLS HYDROLYSIS INITIATES CATABOLISM OF TRIACYLGLYCEROLS
Lipolysis (Lipase) adipose tissue free fatty acids Serum albumin Uptake into tissues Oxidized or reesterified Glycerol Glycerol kinase

4 Overview of acylglycerol biosynthesis

5

6

7 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

8 Choline or ethanolamine must first be activated
Cardiolipin

9 Biosynthesis of cardiolipin

10 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.

11 Biosynthesis of ether lipids

12 Biosynthesis of ether lipids

13 Phospholipases allow degradation & remodeling of phosphoglycerols

14 Metabolism of phosphatidylcholine
(lecithin)

15 Sites of the hydrolytic activity of phospholipases

16 The incorporation of fatty acids into lecithin; by,
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

17 SPHINGOLIPIDS Formed from CERAMIDE

18 Biosynthesis of ceramide.

19 Biosynthesis of sphingomyelin

20 Glycosphingolipids Simple Complex activated sugars active sulfate
Cerebrosides Galactosylceramide (GalCer) Glucosylceramide (GlcCer) Complex Gangliosides Contain a sialic acid, usually Nacetylneuraminic acid activated sugars Glycosyl transferases,Golgi apparatus active sulfate

21 Biosynthesis of galactosylceramide and its sulfo derivative
Biosynthesis of galactosylceramide and its sulfo derivative. (PAPS,“active sulfate,” adenosine 3′-phosphate-5′-phosphosulfate.)

22 Glycosphingolipids Constituents of the outer leaflet of plasma membranes Cell adhesion and cell recognition Antigens Receptors

23 Biosynthesis of gangliosides

24 CLINICAL ASPECTS Respiratory Distress Syndrome Multiple Sclerosis
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

25 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

26 Examples of sphingolipidoses

27 SUMMARY Triacylglycerols
The major energy-storing lipids Phosphoglycerols, sphingomyelin, and glycosphingolipids Amphipathic Have structural functions in cell membranes Specialized roles

28 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

29 Sphingolipids Gangliosides Disease processes
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

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