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Metabolism of acylglycerols and sphingolipids

Metabolism of acylglycerols and sphingolipids. Alice Skoumalová. Types of glycerolipids and sphingolipids. Triacylglycerols function as energy reserves adipose tissue (storage of triacylglycerol), lipoproteins. 2. Glycerophospholipids the major lipid components of biological membranes

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Metabolism of acylglycerols and sphingolipids

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  1. Metabolism of acylglycerols and sphingolipids Alice Skoumalová

  2. Types of glycerolipids and sphingolipids

  3. 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 PIP2)

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

  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 CO2 and water in tissues • Prolongedfasting - ketone bodies (from acetyl CoA), gluconeogenese (glycerol)

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

  17. Degradation of glycerophospholipids Phospholipases located in cell membranes or in lysosomes Phospholipase A2 Phospholipase C Arachidonic acid - eicosanoids Hydrolysis of PIP2 - the second messengers Repair mechanism for membrane DAG and inositol PIP2 lipids damaged by free radicals

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

  19. Degradation of sphingolipids • by lysosomal enzymes (deficienties result in lysosomal storage disease = sphingolipidoses) Sphingolipidoses genetic mutations, mental retardation, death

  20. Tay-Sachs disease • ganglioside accumulation in neurons

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

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

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