Phospholipids and lipid storage diseases

What is the basic structure of a glycerophospholipid?

Glycerol + 2 fatty acids + phosphate + alcohol

What is the function of glycerophospholipids?

Membrane lipids

What is the hydrophilic part of a phospholipid?

Polar head

What is the hydrophobic part of a phospholipid?

Fatty acid tails

What alcohol forms lecithin?

Choline

What alcohol forms cephalin?

Ethanolamine

What alcohol forms cardiolipin?

Glycerol

Name four common phospholipid alcohols.

Choline, ethanolamine, serine, inositol

What are phospholipids important components of besides membranes?

Lipoproteins, bile, surfactant

Which phospholipid deficiency contributes to neonatal respiratory distress syndrome?

Lung surfactant phospholipids

What enzyme removes a fatty acid from phospholipids at position 1?

Phospholipase A1

What enzyme removes a fatty acid from phospholipids at position 2?

Phospholipase A2

What are the products of phospholipase A action?

Free fatty acid and lysophospholipid

What is another name for phospholipase B?

Lysophospholipase

What are the products of phospholipase C action?

DAG and phosphoryl alcohol

What are the products of phospholipase D action?

Phosphatidic acid and alcohol

Where is phospholipase A2 found?

Pancreatic juice and snake venom

Which phospholipase is a major bacterial toxin?

Phospholipase C

Which phospholipase is involved in signal transduction?

Phospholipase D

What does LCAT stand for?

Lecithin cholesterol acyltransferase

What does LCAT produce from cholesterol?

Cholesterol ester

What is lysolecithin?

Lecithin missing one fatty acid

What is the backbone of ether glycerophospholipids?

Ether-linked glycerol

Name two ether glycerophospholipids.

PAF and plasmalogens

What does PAF stand for?

Platelet-activating factor

Which cells release PAF?

Phagocytes

What effect does PAF have on platelets?

Aggregation

What cardiovascular effect does PAF cause?

Hypotension

PAF is associated with what immune reaction?

Allergic responses

Where are plasmalogens synthesized?

Peroxisomes

Which tissues contain abundant plasmalogens?

Heart and nervous tissue

Which organ has low plasmalogen levels?

Liver

What syndrome causes decreased plasmalogens?

Zellweger syndrome

What is the prognosis of Zellweger syndrome?

Early death

Which phospholipid is a major component of the inner mitochondrial membrane?

Cardiolipin

What is the function of cardiolipin?

Mitochondrial enzyme function

Cardiolipin stabilizes which mitochondrial complex?

TOM complex

What does TOM stand for?

Translocase of outer membrane

What is the most abundant phospholipid?

Phosphatidylcholine

What is another name for phosphatidylcholine?

Lecithin

What is the main role of phosphatidylcholine?

Bilayer formation

Which phospholipid is important in signal transduction?

Phosphatidylinositol

Which phospholipid acts as a pro-inflammatory lipid?

Phosphatidic acid

Which disease shows decreased phospholipids and sphingolipids in white matter?

Multiple sclerosis

What happens to CSF phospholipids in multiple sclerosis?

Increased

What is the backbone of sphingolipids?

Sphingosine

How does sphingosine differ from glycerol?

Amino alcohol

What are two functions of sphingolipids?

Cell communication and blood group antigens

What are the precursors of sphingosine?

Palmitate and serine

What is the most common sphingophospholipid?

Sphingomyelin

What is the phosphoryl alcohol in sphingomyelin?

Phosphorylcholine

What is the precursor of sphingomyelin?

Ceramide

Where is sphingomyelin synthesized?

Golgi apparatus

What is the simplest glycosphingolipid?

Cerebroside

Which sugar is present in extraneural cerebrosides?

Glucose

Which sugar is present in myelin cerebrosides?

Galactose

What are sulfatides?

Sulfated galactocerebrosides

Where are sulfatides abundant?

Myelin

What is the usual fatty acid length in glycosphingolipids?

22–26 carbons

Are cerebrosides neutral or charged?

Neutral

What are gangliosides?

Complex glycosphingolipids

What sugar component makes gangliosides complex?

Oligosaccharides with sialic acid

What is the charge of gangliosides at physiologic pH?

Negative

What percentage of brain lipids are gangliosides?

5–8%

What is ceramide?

Sphingosine + fatty acid

Where are sphingolipids degraded?

Lysosomes

What causes lipid storage diseases?

Lysosomal enzyme deficiencies

What accumulates in lipid storage diseases?

Sphingolipids

Which enzyme is deficient in Krabbe disease?

β-Galactosidase

What is the hallmark cell of Krabbe disease?

Globoid cells

What happens to myelin in Krabbe disease?

Nearly absent

What neurologic feature occurs in Krabbe disease?

Psychomotor retardation

Which enzyme is deficient in Gaucher disease?

β-Glucosidase

What accumulates in Gaucher disease?

Glucocerebrosides

What is the characteristic macrophage appearance in Gaucher disease?

Crinkled paper

What organs enlarge in Gaucher disease?

Liver and spleen

What bone finding occurs in Gaucher disease?

Long bone erosion

Which enzyme is deficient in Niemann-Pick disease?

Sphingomyelinase

What accumulates in Niemann-Pick disease?

Sphingomyelin

What organs enlarge in Niemann-Pick disease?

Liver and spleen

What is the characteristic macrophage appearance in Niemann-Pick disease?

Foamy macrophages

What is the prognosis of Niemann-Pick disease?

Fatal early in life

Which enzyme is deficient in Fabry disease?

α-Galactosidase

Which enzyme is deficient in metachromatic leukodystrophy?

Arylsulfatase A

What accumulates in metachromatic leukodystrophy?

Sulfatides

What is a key neurologic feature of metachromatic leukodystrophy?

Demyelination

What peripheral nervous system feature occurs in metachromatic leukodystrophy?

Peripheral neuropathy

What is the usual outcome of metachromatic leukodystrophy?

Death in first decade

Which enzyme is deficient in Tay-Sachs disease?

Hexosaminidase A

What accumulates in Tay-Sachs disease?

GM2 ganglioside

What retinal finding is classic for Tay-Sachs disease?

Cherry-red macula

What visual symptom occurs in Tay-Sachs disease?

Blindness

What ethnic group is commonly affected by Tay-Sachs disease?

Ashkenazi Jews

What is the prognosis of Tay-Sachs disease?

Fatal in childhood

Which lipid storage disease has cherry-red macula and no hepatosplenomegaly?

Tay-Sachs disease

Which lipid storage disease has crinkled paper macrophages?

Gaucher disease

Which lipid storage disease has foamy macrophages?

Niemann-Pick disease

Which lipid storage disease has globoid cells?

Krabbe disease

Which lipid storage disease is caused by arylsulfatase A deficiency?

Metachromatic leukodystrophy

Which lipid storage disease is caused by α-galactosidase deficiency?

Fabry disease