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Metabolism of acylglycerols and sphingolipids
Alice Skoumalová
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Types of glycerolipids and sphingolipids
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1. Triacylglycerols function as energy reserves
adipose tissue (storage of triacylglycerol), lipoproteins
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2. Glycerophospholipids the major lipid components of biological membranes
lipoproteins, bile, lung surfactant
source of PUFA (eicosanoids)
signal transmission (hydrolysis of PIP2)
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3. Plasmalogens myelin, heart muscle
PAF (Platelet-activating factor)
released from phagocytic blood cells in respons to varios stimuli (platelet aggregation, edema, hypotension)
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4. Sphingomyelins (sphingophospholipids) membrane components (make up 10-20% of plasma membrane lipids)
myelinSphingosine
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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
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FA (from the diet, synthetized) TG glycerophospholipides sphingolipides
Lipogenesis - the synthesis of triacylglycerols from glucose (mainly in the liver)
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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
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Dephosphorylation:
Addition of another acyl:
Formation of TG:
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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
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Lipoproteins
Function: Lipid transport (cholesterol, cholesterol esters, triacylglycerols, phospholipids)
Structure:
A nucleus: triacylglycerols, cholesterol esters
A shell: phospholipids, apoproteins, cholesterol
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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
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Storage of TG in adipose tissue
Insulin
glucose transport into cells
synthesis and secretion of LPL
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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
Prolonged fasting - ketone bodies (from acetyl CoA), gluconeogenese (glycerol)
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2. Phospholipid interconversions:
Synthesis of glycerophospholipids
1. Phosphatidic acid - addition of a head group to the molecule
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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
Degradation of glycerophospholipids
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Synthesis of sphingolipids
In the Golgi complex (membranes of SV)
Formation of ceramide:
Precursors:
Serine + Palmitoyl CoA condense
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Degradation of sphingolipids
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 GM1-β-Galactosidase GM1-Ganglioside
Tay-Sachs disease Hexosaminidase A GM2-Ganglioside
Tay-Sachs variant Hexosaminid. A and B GM2-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 Sphingomyelinase Sphingomyelin
Farber disease Ceramidase Ceramide
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Tay-Sachs disease
ganglioside accumulation in neurons
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Summary
• Triacylglycerols (synthesis)
• Storage of TG in adipose tissue
• Release of FA from adipose tissue
• Glycerophospholipids (synthesis, degradation)
• Sphingolipids (synthesis, degradation)
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Pictures used in the presentation:
Marks´ Basic Medical Biochemistry, A Clinical Approach, third edition, 2009 (M. Lieberman, A.D. Marks)