Metabolism of Acylglycerols and Sphingolipids: DR - Qasim AL-Daami

Metabolism of acylglycerols
and sphingolipids
Dr.Qasim AL-Daami
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)
 myelin Sphingosine
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
Lipogenesis - the synthesis of triacylglycerols from glucose (mainly in the liver)
FA (from the diet, synthetized)

 TG
 glycerophospholipides
 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
 proteins synthesized on the rough

ER are packaged with TG in the ER
and GC to form VLDL
VLDL
TG, cholesterol, phospholipids and
proteins
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)
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 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
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)

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Metabolism of acylglycerols

PAF (Platelet-activating factor)

FA (from the diet, synthetized)

in the smooth endoplasmic reticulum

The sources of glycerol 3-phosphate:

Addition of another acyl:

 proteins synthesized on the rough

A nucleus: triacylglycerols, cholesterol esters

In the Golgi complex (membranes of SV)

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