Metabolism of acylglycerols and sphingolipids
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Transcript of Metabolism of acylglycerols and sphingolipids
Metabolism of acylglycerols and sphingolipids
Alice Skoumalová
Types of glycerolipids and sphingolipids
1. Triacylglycerols function as energy reserves
adipose tissue (storage of triacylglycerol), lipoproteins
2. Glycerophospholipids the major lipid components of biological membranes
lipoproteins, bile, lung surfactant
source of PUFA (eicosanoids)
signal transmission (hydrolysis of PIP2)
3. Plasmalogens myelin, heart muscle
PAF (Platelet-activating factor)
released from phagocytic blood cells in respons to varios stimuli (platelet aggregation, edema, hypotension)
4. Sphingomyelins (sphingophospholipids) membrane components (make up 10-20% of plasma membrane lipids)
myelinSphingosine
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
FA (from the diet, synthetized) TG glycerophospholipides sphingolipides
Lipogenesis - the synthesis of triacylglycerols from glucose (mainly in the liver)
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
proteins synthesized on the rough ER are packaged with TG in the ER and GC to form VLDL
TG, cholesterol, phospholipids and proteins
VLDL
Lipoproteins
Function: Lipid transport (cholesterol, cholesterol esters, triacylglycerols, phospholipids)
Structure:
A nucleus: triacylglycerols, cholesterol esters
A shell: phospholipids, apoproteins, cholesterol
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
Storage of TG in adipose tissue
Insulin
glucose transport into cells
synthesis and secretion of LPL
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)
2. Phospholipid interconversions:
Synthesis of glycerophospholipids
1. Phosphatidic acid - addition of a head group to the molecule
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
Synthesis of sphingolipids
In the Golgi complex (membranes of SV)
Formation of ceramide:
Precursors:
Serine + Palmitoyl CoA condense
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
Tay-Sachs disease
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)