Metabolism of acylglycerols and sphingolipids Alice Skoumalov Types

Metabolism of acylglycerols and sphingolipids Alice Skoumalová

Types of glycerolipids and sphingolipids

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

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

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

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

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

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

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

Dephosphorylation: Addition of another acyl: Formation of TG:

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

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

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

Storage of TG in adipose tissue Insulin Ø glucose transport into cells Ø synthesis and secretion of LPL

Release of FA from adipose TG ↓Insulin, ↑Glucagon Ø intracellular c. AMP 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 Co. A), gluconeogenese (glycerol)

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

Degradation of glycerophospholipids Phospholipases located in cell membranes or in lysosomes Phospholipase A 2 Phospholipase C Arachidonic acid - eicosanoids Hydrolysis of PIP 2 - the second messengers Repair mechanism for membrane DAG and inositol PIP 2 lipids damaged by free radicals

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

Degradation of sphingolipids Ø by lysosomal enzymes (deficienties result in lysosomal storage disease = sphingolipidoses) Sphingolipidoses genetic mutations, mental retardation, death Nemoc Deficit enzymu Kumulující lipid Fucosidosis α-Fucosidase H-Isoantigen Generalized gangliosidosis GM 1 -β-Galactosidase GM 1 -Ganglioside Tay-Sachs disease Hexosaminidase A GM 2 -Ganglioside Tay-Sachs variant Hexosaminid. A and B GM 2 -Ganglioside Fabry disease α-Galactosidase Globotriaosylceramide Ceramide lactoside lipidosis Ceramide lactosidase Ceramide laktoside Metachromatic leukodystrophy Arylsulfatase A 3 -Sulfogalactosylceramide Krabbe disease β-Galactosidase Galactosylceramide Gaucher disease β-Glucosidase Glucosylceramide Niemann-Pick disease Sphingomyelin Farber disease Ceramide

Tay-Sachs disease Ø ganglioside accumulation in neurons

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

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