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 Lipolysis (Lipase) adipose tissue free fatty acids Serum albumin Uptake into tissues Oxidized or reesterified Glycerol Glycerol kinase

Overview of acylglycerol biosynthesis

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

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

SPHINGOLIPIDS Formed from CERAMIDE

Biosynthesis of ceramide.

Biosynthesis of sphingomyelin

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

Biosynthesis of galactosylceramide and its sulfo derivative 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 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

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 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