1. Metabolism of acylglycerols and sphingolipids Alice Skoumalová

2. Types of glycerolipids and sphingolipids

3. 1.Triacylglycerols  function as energy reserves  adipose tissue (storage of triacylglycerol), lipoproteins

4. 2. Glycerophospholipids  the major lipid components of biological membranes  lipoproteins, bile, lung surfactant  source of PUFA (eicosanoids)  signal transmission (hydrolysis of PIP 2 )

5. 3. Plasmalogens  myelin, heart muscle PAF (Platelet-activating factor)  released from phagocytic blood cells in respons to varios stimuli (platelet aggregation, edema, hypotension)

6. 4. Sphingomyelins (sphingophospholipids)  membrane components (make up 10-20% of plasma membrane lipids)  myelin Sphingosine

7. 4. Glycolipids  the surfaces of cell membranes, receptors (hormons, cholera toxin), specific determinats of cell-cell recognition, the antigenic determinants of the ABO blood groups  cerebrosides, sulfatides, gangliosides

8. FA (from the diet, synthetized)  TG  glycerophospholipides  sphingolipides Lipogenesis - the synthesis of triacylglycerols from glucose (mainly in the liver)

9. Synthesis of TG in the smooth endoplasmic reticulum The sources of glycerol 3-phosphate: 1. the phosphorylation of glycerol (glycerol kinase) liver 2. the reduction of dihydroxyacetone phosphate (from glycolysis) liver, adipose tissue Phosphatidic acid - the precursor for: 1. TG 2. glycerophospholipids

10. Dephosphorylation: Addition of another acyl: Formation of TG:

11. Synthesis, processing and secretion of VLDL  proteins synthesized on the rough ER are packaged with TG in the ER and GC to form VLDL TG, cholesterol, phospholipids and proteins VLDL

12. Lipoproteins Function:  Lipid transport (cholesterol, cholesterol esters, triacylglycerols, phospholipids) Structure: A nucleus: triacylglycerols, cholesterol esters A shell: phospholipids, apoproteins, cholesterol

13. Fate of VLDL TG Lipoprotein lipase  present on the lining cells of the capillaries (in adipose and sceletal muscle tissue)  coenzyme Apo C-II (from HDL)  hydrolyses TG from VLDL and chylomicrons

14. Storage of TG in adipose tissue Insulin  glucose transport into cells  synthesis and secretion of LPL

15. Release of FA from adipose TG ↓Insulin, ↑Glucagon  intracellular cAMP increases - activates protein kinase A - phosphorylates hormone-sensitive lipase FA - complexes with albumin, oxidized to CO 2 and water in tissues Prolonged fasting - ketone bodies (from acetyl CoA), gluconeogenese (glycerol)

16. 2. Phospholipid interconversions: Synthesis of glycerophospholipids 1. Phosphatidic acid - addition of a head group to the molecule

17. Phospholipases located in cell membranes or in lysosomes Phospholipase A2Phospholipase C Arachidonic acid - eicosanoidsHydrolysis of PIP 2 - the second messengers Repair mechanism for membraneDAG and inositol PIP 2 lipids damaged by free radicals Degradation of glycerophospholipids

18. Synthesis of sphingolipids In the Golgi complex (membranes of SV) Formation of ceramide: Precursors: Serine + Palmitoyl CoA condense

20. Degradation of sphingolipids  by lysosomal enzymes (deficienties result in lysosomal storage disease = sphingolipidoses) Sphingolipidoses genetic mutations, mental retardation, death NemocDeficit enzymuKumulující lipid Fucosidosisα-FucosidaseH-Isoantigen Generalized gangliosidosisG M1 -β-GalactosidaseG M1 -Ganglioside Tay-Sachs diseaseHexosaminidase AG M2 -Ganglioside Tay-Sachs variantHexosaminid. A and BG M2 -Ganglioside Fabry diseaseα-GalactosidaseGlobotriaosylceramide Ceramide lactoside lipidosisCeramide lactosidaseCeramide laktoside Metachromatic leukodystrophyArylsulfatase A3-Sulfogalactosylceramide Krabbe diseaseβ-GalactosidaseGalactosylceramide Gaucher diseaseβ-GlucosidaseGlucosylceramide Niemann-Pick diseaseSphingomyelinaseSphingomyelin Farber diseaseCeramidaseCeramide

21. Tay-Sachs disease  ganglioside accumulation in neurons

22. Summary Triacylglycerols (synthesis) Storage of TG in adipose tissue Release of FA from adipose tissue Glycerophospholipids (synthesis, degradation) Sphingolipids (synthesis, degradation)

23. Pictures used in the presentation: Marks´ Basic Medical Biochemistry, A Clinical Approach, third edition, 2009 (M. Lieberman, A.D. Marks)