Block 3 PLs and SLs Flashcards
What’s the difference between a glyceroPL and a sphingoPL?
Glycerol or sphingosine as backbone
What are the components of a glyceroPL?
Glycerol backbone, head group (small polar with OH ester linked to PO4), FA 1 (mostly sat), FA 2 (PUFA)
Where are PLs synthesized?
Cytosolic face ER, then transported to final destination
What is phosphatidic acid?
PA; simplest phosphoglyceride (X=H), precursor of all others
What are PLs formed from? Give examples.
PA esterified to alcohol (polar); PS (serine), PE (ethanolamine), PC/lecithin (choline), etc.
What is a lysophosphoglyceride?
If either R1 or R2 is removed (e.g. lysolecithin)
What is cardiolipin? What is the function?
2 molecules esterified PS; has 3 glycerols, 4 FFAs, in IMM; proton trap buffering pH near PM in IMM
What happens when cardiolipin is peroxidated?
Apoptosis triggered; CL oxygenase -> perox unsat acyl chain -> cytC pore -> binds IP3 -> Ca release ER -> more cytC release
What are ether PLs?
FA attached at C1 in ether not ester; sat (alkyl) or unsat (alkenyl) alc in sn-1 position
What type of PLs are plasmalogens? Where are they found?
Alkenyl ether PLs, 20% mammal glyceroPLs; myelin has ethanolamine plasmalogens, heart mm choline plasmalogens
What is platelet activating factor (PAF)?
1-alkyl-2-acetyl-PC; potent platelet agg, degran; mediates acute inflamm & ana shock; neutros, dust cells -> superoxide anion; TM signaling -> act PLipase -> PL degradation
What is surfactant?
DPPC; secreted by type 2 pneumocytes; 2 saturated palmitic acid v risk for ROS oxidation; also contains PtGlycerol, chol, surfactant proteins Sp-A,B,C
What is respiratory distress syndrome?
Hyaline membrane disease in infants, inadequate lung maturation in premies; increased PC/SPH ratio in amniotic fluid indicates lung maturation (>2); 15% neonatal deaths in Western countries
What is respiratory failure?
In adults, damaged/destroyed surfactant-producing pneumocytes b/c immunosuppressive meds or chemo drugs
Why are PA and CTP important in glyceroPL synthesis?
PA is precursor of most, CTP required as activator of polar head groups or hydrophobic tail
How is PA synthesized?
Liver: glycerol -> Gly3P
Liver, adipose: glucose -> DHAP -> Gly3P + 2 FaCoA = PA
PL -> PLase D -> PA
What is the product of CTP activating polar head or hydrophobic tail?
Head: PA -> DAG + CTP-head -> glyceroPL = PC, PE
Tail: PA -> CDP-DAG + head group -> glyceroPL = PI, CL
How are PE and PS interconverted?
Reversible, Ca-activated “base exchange” of free serine for ethanolamine of PE; to make PS for membrane synthesis
How is membrane PS converted to PC?
PS decarboxylated to PE, undergoes 3 methylations (donor SAM) -> PC + SAH
What aa is required to make PC? What is the salvage pathway?
Methionine (essential, often deficient)
CDP-choline pathway for PC synth because activates free choline for reincorporation into membrane lipids
What are the 3 sources of choline?
Liver synth (need Met, Bvit); recycled choline (during turnover PC, SM, ACh reincorporated via salvage); dietary (PC/lecithin in meat, eggs, veg; def = brain dev, memory)
What is a phospholipase? What do the major classes do?
Degrade glyceroPLs
A1/2 remove FA from C1/2
C cleaves PDE bond b/t C3 & P
D cleaves PDE bond b/t P and polar head
What are products of PLA2? Why is this important?
FFA and lysoPL (amphipathic detergents); major mech for cytotoxicity bee/snake venoms; contribute to PL synth (membrane remodel), release AA for eicosanoid synth, major mech removal damaged PUFA
What are the different types of PLA2?
Cytosolic: releases AA for eicosanoid synth, act by ^ [Ca], P by MAPK ^ activity
Ca-ind intracellular: turnover/remodeling cellular PLs
Secretory: extracellular, response to sepsis/inflam, high [ ] in arthritic synovial fluid
Pancreatic: digestive, secreted as zymogen
Describe the structure of a sphingolipid.
Backbone of sphingosine, 1 FA (palmitic 16:0, stearic 18:0, or nerving 24:1), polar head of phosphocholine (SphPL) or carb (glycolipid)
What are the physiological roles of SLs?
ABO, receptors for intercellular comm, SM major in nervous tissue, more sat than PLs = specialized membrane domains, ceramide 2nd mess signals apoptosis/differentiation
How does SM affect chol?
Chol intx with SM in PM bc highly sat LCFA + sphingoid base -> gel phase domains (+ chol -> liquid) caveolae and rafts with PKC, LDL-R, eNOS, etc.
How is SM degraded?
SMase is lysosomal, deficient in Niemann-Pick type 1 (type A most severe)
What are symptoms of Niemann Pick type 1?
SMase def; enlarged liver and spleen due to lipid, severe mental retardation, death in early childhood
What are glycolipids? What’s the difference between cerebrosides and gangliosides?
GL: one or more sugars + ceramide (replace phosphocholine as head)
C: ceramide + 1 sugar
G: ceramide + complex, branched carb chain
