Lecture 21: Synthesis of Membrane Lipids and Sphingolipidoses

Lipid

A group of organic compounds that are insoluble in water and soluble in organic solvents, important for energy storage and cell membrane structure.

Sphingosine

A backbone structure for certain lipids, formed from serine and a fatty acid.

Ceramide

A type of sphingolipid formed when a fatty acid is added to sphingosine.

Glycolipid

A lipid containing a carbohydrate group; lacks phosphate groups.

Myelin

A fatty substance that surrounds nerve fibers, enhancing the speed of signal transmission.

Choline

A nutrient important for the synthesis of phospholipids and myelin.

Galactocerebroside

A type of glycolipid formed by adding galactose to ceramide.

Ganglioside

A type of glycolipid that contains sialic acid, important in cell recognition.

Lysosomes

Organelles that contain digestive enzymes to degrade cellular waste and lipids.

Tay-Sachs Disease

A genetic disorder caused by the deficiency of a specific enzyme leading to the accumulation of GM2 gangliosides in nerve cells.

Niemann-Pick Disease

A genetic disorder resulting from the inability to metabolize sphingomyelin, leading to its accumulation in cells.

Fabry Disease

An X-linked genetic disorder where an enzyme deficiency leads to the accumulation of certain lipids, causing various symptoms.

Gaucher Disease

A genetic disorder characterized by the accumulation of glucocerebrosides due to enzyme deficiency.

Krabbe Disease

A rare genetic disorder caused by a deficiency of the enzyme galactocerebrosidase, leading to neurological damage.

Sphingomyelin

A type of phospholipid involved in the formation of cell membranes, particularly in myelin sheaths.

Lysosomal enzyme deficiency

A condition where specific enzymes required to break down certain lipids are absent or nonfunctional, leading to storage disorders.

Hepatosplenomegaly

Enlargement of the liver and spleen, often seen in lysosomal storage diseases.

Cherry-red spot

A classic clinical sign found in some lysosomal storage diseases, seen in the macula of the eye.

Inborn error of metabolism

A genetic condition resulting from a deficiency of an enzyme critical for metabolism.

Are lipids water-soluble?

No.

Are lipids organic solvent-soluble?

Yes.

Lipids are for what storage?

Energy.

Lipids form which structure?

Cell membrane.

Sphingosine is backbone for what?

Lipids.

What forms sphingosine?

Serine and fatty acid.

Ceramide is what type of lipid?

Sphingolipid.

Ceramide: sphingosine + what?

Fatty acid.

Glycolipids contain what group?

Carbohydrate.

Glycolipids lack what group?

Phosphate.

Myelin surrounds what fibers?

Nerve.

Myelin enhances what transmission?

Signal speed.

Choline synthesizes phospholipids and?

Myelin.

Galactocerebroside: galactose + what?

Ceramide.

Galactocerebroside is what type?

Glycolipid.

Gangliosides contain which acid?

Sialic.

Gangliosides aid in cell…?

Recognition.

Lysosomes contain what enzymes?

Digestive.

Lysosomes degrade cellular waste and?

Lipids.

Tay-Sachs: deficiency of what?

Enzyme.

Tay-Sachs: accumulation of what?

GM2 gangliosides.

Tay-Sachs: accumulation in what cells?

Nerve.

Niemann-Pick: cannot metabolize what?

Sphingomyelin.

Niemann-Pick: accumulation where?

Cells.

Fabry Disease inheritance?

X-linked.

Fabry Disease: enzyme deficiency + what?

Lipid accumulation.

Gaucher Disease: accumulation of what?

Glucocerebrosides.

Gaucher Disease caused by?

Enzyme deficiency.

Krabbe Disease: deficient enzyme?

Galactocerebrosidase.

Krabbe Disease leads to what damage?

Neurological.

Sphingomyelin is what type?

Phospholipid.

Sphingomyelin forms what membranes?

Cell.

Sphingomyelin in what sheaths?

Myelin.

Enzyme deficiency leads to what?

Storage disorders.

Hepatosplenomegaly: enlargement of?

Liver and spleen.

Hepatosplenomegaly seen in what diseases?

Lysosomal storage.

Cherry-red spot is a sign for?

Lysosomal storage diseases.

Cherry-red spot seen in what eye part?

Macula.

Inborn error of metabolism: what condition?

Genetic.

Inborn error of metabolism: due to what?

Enzyme deficiency.

What are glycerophospholipids?

Abundant membrane phospholipids

Glycerophospholipid components?

Glycerol, 2 FA, phosphate

FA at sn-1 position?

Saturated

FA at sn-2 position?

Unsaturated

Phospholipid synthesis site?

Cytosolic face of ER

Glycerophospholipid precursor?

Phosphatidic acid

Phosphatidic acid starts from?

Glycerol 3-phosphate

Most abundant body phospholipid?

Phosphatidylcholine

Phosphatidylcholine made from?

Phosphatidylethanolamine methylation

What is lung surfactant?

Mixture reducing surface tension

Surfactant prevents what?

Alveoli collapse

Surfactant secreted by?

Type II pneumocytes

Main lung surfactant phospholipid?

Dipalmitoylphosphatidylcholine (DPPC)

DPPC characteristic?

Two palmitoyl fatty acids

Surfactant spreading proteins?

SP-B, SP-C

Surfactant immune defense proteins?

SP-A, SP-D

Surfactant deficiency causes?

Neonatal respiratory distress syndrome

Fetal lung maturity measured by?

Lecithin/sphingomyelin ratio

Mature L/S ratio?

$$>2$$

What insulates nerve axons?

Myelin sheath

Myelinating cells?

Oligodendrocytes (CNS), Schwann (PNS)

CNS demyelination disease?

Multiple sclerosis

Phospholipase cleaves FA at C1?

PLA1

Phospholipase cleaves FA at C2?

PLA2

Phospholipase cleaves phosphate group?

PLC

Phospholipase cleaves head group?

PLD

Enzyme producing arachidonic acid?

PLA2

Arachidonic acid precursor to?

Eicosanoids

PLC second messengers?

DAG, IP3

PLD product?

Phosphatidic acid

Sphingolipid precursor?

Ceramide

Sphingosine formed from?

Serine + palmitoyl-CoA

Sphingosine synthesis enzyme?

Serine palmitoyltransferase

Ceramide + phosphatidylcholine forms?

Sphingomyelin

Ceramide + UDP-glucose forms?

Glucocerebroside

Ceramide + sugars forms?

Glycosphingolipids

Sphingolipid synthesis location?

ER & Golgi

Simplest glycosphingolipids?

Cerebrosides

Cerebroside with glucose?

Glucocerebroside

Cerebroside with galactose?

Galactocerebroside

Sulfated cerebrosides?

Sulfatides