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Biochemistry 309: Sphingo-Reality

What is a sphingosine?
-an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phospholipid.
-made of palmitate and serine combined.
-it is aliphatic

Membrane rafts = areas in a membrane with less fluidity, or near-crystalline consistence. The rafts contain tightly packed cholesterol and sphingolipids. Ceramide-based lipids self-aggregate in cell membranes and form separate phases less fluid than the bulk phospholipids. These sphingolipid-based microdomains, or "lipid rafts" were originally proposed to sort membrane proteins along the cellular pathways of membrane transport.

What is a sphingolipid?
--constitute a 20-35 molar fraction of plasma membrane lipids
--often found in neural tissue (fx: signal transmission and cell recognition)
--commonly believed to protect the cell surface against harmful environmental factors by forming a mechanically stable and chemically resistant outer leaflet of the plasma membrane lipid bilayer.
--some glycosphingolipids are involved in cell recognition and signaling.
--ceramide and sphingosine-1-phosphate, have been shown to be important mediators in the signaling cascades involved in apoptosis, proliferation, and stress responses
--synthesized in the ER and Golgi apparatus
--enriched in the plasma membrane and in endosomes, where they perform many of their functions, thus travelling and evolving between organelles
--transported via vesicles and monomeric transport in the cytosol
--virtually absent from mitochondria and the ER

Three main types of sphingolipids:
1. ceramides, the simplest type, a fatty acid chain attached through an amide linkage to sphingosine.
2. sphingomyelins have a phosphorylcholine or phosphoroethanolamine molecule esterified to the 1-hydroxy group of a ceramide
3. glycosphingolipids, which have different head groups, are ceramides with one or more sugar residues joined in a β-glycosidic linkage at the 1-hydroxyl position. Two kinds of these are cerebrosides and gangliosides which have carbohydrate headgroups, ie they are glycolipids.

A disease caused by a disorder in sphingolipid metabolism: Gaucher's disease, most common of the lipid storage diseases. It is caused by a defect in a housekeeping gene which results in an enzyme deficiency. The lack of enzyme leads to an accumulation of its substrate, a fatty substance called glucocerebroside, which is a component of the membranes of red and white blood cells. Glucocerebroside gunks up the spleen, liver, kidneys, lungs, brain and bone marrow. Symptoms: enlarged spleen and liver, liver malfunction, skeletal disorders and painful bone lesions, severe neurologic complications, swelling of lymph nodes and (occasionally) adjacent joints, distended abdomen, a brownish tint to the skin, anemia, low blood platelets and yellow fatty deposits on the sclera. Affects males and females equally. It is the most common lysosomal storage disease. It is named after the French doctor who originally described it in 1882. There are 3 types and type 1 occurs mostly among the Ashkenazi Jews and Norrbottnian Swedes. Treatment for types 1 and 3 is enzyme replacement.

What are N-linked phospholipids?

What are O-linked phospholipids?
--sphingosine is one: The sphingosine backbone is O-linked to a (usually) charged head group such as ethanolamine, serine, or choline.

pp240, 241, 247

CHOLESTEROL is not a sphingolipid but rather a steroid
--a planar molecule w/ 4 rings
--gets sandwiched between phospholipids in membrane
--120g in average human body
--CNS is 10% cholesterol by weight
--LDL = low density lipoprotein (the "bad" kind) transports cholesterol from the liver to tissue, and too much can precipitate as plaque and cause athlerosclerosis
--HDL = high density lipoprotein (the "good" kind) takes excess cholesterol to the liver where bile acids break it down for excretion
--vitamins D2, D3, look a lot like it

--PC = phsophatidyle choline = lecithin - in egg stabilizes the emulsion - has no double bonds (16:0)

emulsion = mixture of two+ things in the same phase, such as oil and water

The packing density of lipids is partly a function of temperature, and for any one lipid there's a distinct point at which it melts. Because membranes have a variety of lipids in them, they have a broader range of temperature at which they stay liquid. Cholesterol broadens that range even more.

isoprene is not part of membrane but is subunit of ubiquinone from which vitamin A (retinol) and vitamin K (phylloquinone) are synthesized??



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