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)