Sphingolipids - UTSW
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| What are the 3 major classes of membrane lipids? | Phospholipids (65%), Cholesterol (25%), & Sphingolipids (10%)
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| What are the 2 types of sphingolipid? | Sphingomyelin & Glycosphingolipids
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| How do sphingomyelin & glycosphingolipids differ structurally? | Both have choline & Glycosphingolipids have sugars (glucose & hexose)
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| How are glycosphingolipids unique? | They are amphipathic (hydro philic& phobic)
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| What is the structure of sphingolipids? | sphingosine (18C palmitate) connected by amide (serine) linkage to long chain fatty acid
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| What are the 3 classes of glycosphingolipids? | cerebrosides (1 sugar: galactose (neurons) or glucose (non-neurons)), globosides (linear), gangliosides (branched)
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| What are first 4 steps of sphingolipid synthesis? | 1. Serine + Palmitoyl CoA via Serine palmitoyl transferase *rate limiting*2. 3-ketosphinganine + NADPH via 3-ketosphinganine reductase3. Dihydrosphingosine + RCSCoA via Ceramide synthase4. Dihydroceramide + FAD via Dihydroceramide desaturase
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| What is the 5th step of sphingolipid synthesis? | Branch point: 1. Ceramide + Phosphatidyl Choline via Sphigomyelin synthase leads to sphingomyelin2. Ceramide + UDP Glucose (glycosylation) via glucosylceramide synthase leads to cerebrosides & gangliosides
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| Where does the 5th step of sphingolipid synthesis occur? | Golgi
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| Where do steps 1-4 of sphingolipid synthesis occur? | ER
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| How does the ceramide in sphingolipid synthesis get from the ER to the Golgi? | The ceramide transport protein (CERT)
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| What biological function do sphingolipids perform in the CNS? | They form myelin sheaths (Negatively charged gangliosides in Glial cell membranes)
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| What are the most abundant gangliosides in myelin? | cerebrosides
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| What biological function do sphingolipids perform in the in non-neuronal cells? | Establish asymmetry in lipid composition of membrane & organelles
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| Why is lipid asymetry useful? | Allows the formation of rafts of lipids that have lower phase transition temperature & are stiffer. Membrane proteins associate with rafts
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| What function of sphingolipids is related to hematology? | Glycosphingolipids on the surface of plasma cells form the ABO blood group antigen series
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| How is a person's blood type determined? | The presence or absence of specific sugars attached to gangliosides
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| Where are sphingolipids destroyed? | lysosomes
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| What are lipid storage diseases? | Inherited disorder due to the deficiency/absence of sphingolipid catabolic enzymes causing sphingolipid accumulation
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| What lipid disease involves the lipid gal-gal-glucosylceramide (ganglioside) due to deficient enzyme alpha-galactosidase? | Fabry's
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| What lipid disease involves the lipid glucosylceramide (cerebroside) due to deficient enzyme beta-glucosidase? | Gaucher's
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| What lipid disease involves the lipid sphingomyelin (sphingolipid) due to deficient enzyme sphingomyelinase? | Niemann-Pick
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| What lipid disease involves the lipid GM2 ganglioside (ganglioside) due to deficient enzyme hexosaminidase A? | Tay-Sachs
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| What are the symptoms of Fabry's? | Peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease
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| What are the symptoms of Gaucher's? | Hepatosplenomegaly, aseptic neccrosis of femur, bone crises, Gaucher's cells (macrophages that look like crumpled tissue paper)
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| What are the symptoms of Niemann-Pick? | Progressive neurodegeneration,hepatosplenomegaly, cherry-red spot on macula, foam cells
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| What are the symptoms of Tay-Sachs? | Progressive neurodegeneration,developmental delay, cherry-red spot on macula, lysosomes with onion skin
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| Which lipodoses is the most common? | Gaucher's
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| Which lipodoses are X-linked recessive? | Fabry's & Hunter's
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| Are lipodoses dominant or recessive? | recessive
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| Which lipodoses have hepatosplenomegaly as a symptom? | Gaucher's & Niemann-Pick
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| Which lipodoses have cherry red spot on macula as a symptom? | Tay-Sachs & Niemann-Pick
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| Which lipodoses have progressive neurodegeneration as a symptom? | Tay-Sachs & Niemann-Pick
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