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30 Cards in this Set

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Where are the enzymes for glycerophospholipid synthesis located?
endoplasmic reticulum
The first steps of glycerophospholipid synthesis are similar to the first steps of what other molecules? What are their common intermediates?
Triglyceride synthesis in liver, adipose, and intestine. Common intermediates: glycerol-3-phosphate; 1,2-Diacylglycerol phosphate; 1,2-Diacylglycerol
In glycerophospholipid syntheis, which molecules condense with 1,2-Diacylglycerol (phosphate) and what is required of the molecules involved in condensation?
ethanolamine, choline, inositol

One of the two condensing molecules must be a cytosine derivative. Ethanolamine and choline are CDP derived head groups. In phosphatidylinositol synthesis, 1,2-Diacylglycerol is a CTP derivative.
How are PE and PC synthesized?
Ethanolamine (choline) is phosphorylated.

Cytidyl transferase then converts Ethanolamine-P to Ethanolamine-CDP by pyrophosphate cleavage of CTP to PPi.

Ethanolamine-CDP condenses with 1,2-Diacylglycerol to form PE.
What is different from PE and PC synthesis in PI synthesis?
In PI synthesis, 1,2-DAG is the CTP-derivative. Also, PI can be phosphorylated one or two additional times (at carbons 4 or 5 of the inositol ring) to form PIP or PIP2.
What is the importance of PIP and PIP2?
Phosphorylated inositols modulate cellular activity via a cascade inititated at the cell membrane. Activation of Phospholipase C by receptor mediated signaling degrades PIP2 to IP3 and DAG, which ultimately function to activate protein kinases that phosphorylate proteins. Results in celluar response.
Decarboxylation of phosphatidylserine yields what molecule?
phosphatidylethanolamine
How is arachidonic acid formed from glycerophospholipids and what is it used for?
Phospholipase A2 cleaves the fatty acid group from the 2 position of the DAG portion of PI. Arachidonic acid is used in prostaglandin synthesis.
How does IP3 work as a second messenger?
Causes an increase in intracellular Ca++ released from the Er. Ca++ binds to calmodulin, which activates enzymes and protein kinases.
How does DAG work as a second messenger?
Activates protein kinase C which phosphorylates proteins.
Reaction of CDP-choline with ceramide produces?
sphingomyelin
What is the function of SAM in glycerophospholipid metabolism?
SAM and N-methyltransferase methylate PE, eventually forming phosphatidylcholine.
What is thre result of PE methylation occuring withing the plasma membrane?
the concentration of PC is highest in the outer leaflet of the membrane
What is the primary function of glycerophospholipids?
structural constituents of membranes
How is the core of sphingolipids synthesized?
Palmitoyl-CoA + Serine: decarboxylation yields 3-dehydrospihinganine. Two more reductions yield sphingosine. Adding a long chain fatty acid finally produces ceramide. **amide bond, not an ester bond**
How are cerebrosides made?
Cerebrosides are synthesized be the addition of UDP-glc (glucocerebroside) or UDP-gal (galactocerebroside)
What modifications can be made to cerbrosides?
Sulfate addition to the glucose or galactose yields a sulfatide. *Requires an active sulfate in the form of phosphoadenosine-phosphosulfate (PAPS)
Successive addition of sugars to cerebrosides produce gangliosides of variable length. Common sugars used: galactose, n-acetyl galactosamine, sialic acid.
Tay-Sachs disease...defect?
hexosaminidase A
Gaucher's disease...defect?
glucocerebrosidase
Niemann-Pick disease...defect?
sphyngomyelinase
a class of diseases characterized by partial degradation of sphingolipids that accumulate in the lysosomes of spleen, liver, brain, etc.
lipidoses
Total lipid content of membranes is mainly made up of what molecules and which is the most abundant?
glycerophoshoplipids, sphingolipid, cholesterol (in that order)
Why are triglycerides completely absent from mitochondrial membranes and almost absent from ER and plasma membranes?
The primary function of TGs are to store energy and are thus found in adipose and cytoplasm. Energy is typically not stored in membranes.
Why is cardiolipin (DPG) absent in ER and plasma membranes but significantly present in the inner mitochondrial membrane?
It is required for cytochrome oxidase activity.
What purpose do lipid rafts serve?
high amounts of cholesterol--limit mobility of membrane proteins
What is an example of a membrane with a high protein content relative to lipid content? With high lipid content relative to protein content?
Inner mitochondrial membrane has high protein content. (75 protein: 25 lipid)
Myelin has high lipid content. (80 lipid: 20 protein)
Why would a membrane protein contain more hydrophobic amino acids in one region?
Membrane bound proteins have regions which are associated with the hydrophobic core of the membrane.
Is there a difference in absolute amino acid composition of membrane bound proteins vs. free cytoplasmic proteins?
No, overall composition is similar, however, there are differences in sequence locations of hydrophobic and hydrophilic amino acides because of associated with the membrane.
How do we know a RBC is old?
The negative charge of the surface of RBCs due to sailic acid prevent RBCs from clumping. Sialic acid is removed from RBC glycoproteins as cells age and cells begin to clump. The reticuloendothelial system sees galactose instead of sialic acid and its negative charge and removes these cells from circulation.
How can you experimentally "age" a RBC?
Treat RBC with neuraminidase, which removes sialic acid. (n-acetyl neuraminic acid=sialic acid)