Phospholipids

Question 1

Classes of PL

Answer 1

Alcohol attached to phosphate attached to:
Diacylglycerol - based on phasphatidic acid
Sphingosine - no phosphatidic platform but with Pi (sphingomyelin w/o glycerol backbone)

Question 2

Assembly of PL

Answer 2

Macro components already synth, ER they are put together to golgi to destination

Question 3

Glycerol Spine

Answer 3

All PL based on phosphatidic acid posses glycerol spine
Tails (12-16 C) acyl at C2 unsat
Phosphatidic acid = simplest of all phosphoglycerides and precursor to large family

Question 4

Origins of PT acid

Answer 4

With NADPH

DHAP (glycolysis is main supply), glycerol 3P, diacyl glycerol

Question 5

Creating PLs - pos head groups

Answer 5

Draw pathway, CTP provides activating group w/ CMP leaving Pi behind

Question 6

Synth of Phosphatidyl - choline, ethanolamine, serine

Answer 6

Draw pathway, Choline from diet, SAM donates methyl from methionine

Question 7

Synth of Choline requires SAM

Answer 7

Donor of methyl groups

Condensation of methionine and adenosine releases Pi3 for hydrolysis - very costly

Question 8

Choline and surfactant

Answer 8

Dipalmitoyl-phosphatidyl choline (DPPC) reduces alveolar surface tension

Question 9

Surfactant Synth

Answer 9

ER of lung granular pneumocytes, activated by translocation from cytosol to ER via CTP-phosphocholine cytidyl transferase.

Question 10

Surfactant insuff

Answer 10

Hyaline membrane disease (Resp distress syndrome)

Question 11

Phosphatidic Acid to Cardiolipin and phosphatidyl inositol

Answer 11

Makes IM mito impermeable to H

Cardiolipin lends structural stability (2 PTs, 1 mid glycerol and 4 FA tails = strong acid and stable)

Question 12

Plasmologens

Answer 12

Mammalian ether P-glycerolipids.
DHAP and FA CoA form ester leading to FA exchange for fatty alcohol = stable ether leading to C2 reduced and FA added for ester bond. Double bond forms between C1 and C2 of alkyl group at C1 forms stable plasmalogen: Choline-Pl or Ethanolamine PL. Made in peroxisome.

Question 13

Peroxisomal synth

Answer 13

If PS def leads to zellwegers

Question 14

Platelet Adhesion Factor

Answer 14

Is a plasmalogen
Ether glycero PL but with saturated FA at C1 and acetyl group at C2
Role = Defense, triggers thrombotic reactions

Question 15

Sphingomyelin

Answer 15

Sole Pl with no glycerol - sphingosine is linked to FA via ceramide linkage
FA like tails = good conductor

Question 16

Sphingomyelin pathway

Answer 16

draw

Question 17

Membrane PL’s and signaling

Answer 17

Continual resynth necessary

Phosphatidyl Inositol - Dominate PT acid (CDP activated DAG)

Question 18

PLC

Answer 18

Phospholipase C cleaves C1 leading to IP2 (gates Ca entry) and DAG

Question 19

Phosphatidyl Inositol

Answer 19

Also a GPI anchor
Special soluble water sugars create stable tether
Pi gorups also function in EC space

Question 20

PL signal pathway

Answer 20

On paper

Question 21

Degradation of PL

Answer 21

Phospholipases (PLs) - all tissues, panc juice etc

PLA2 - Functions in defense and inflammation, releases eiconosol FA (20C) and Arachidonic Acid. Inhib by glucocorticoids

Lysosomal Phosphodinase - Sphingomyelinase in lysosome

PLC - activated by PIP2 = 2nd msgrs

Question 22

Lysosomal Sphingomyeline

Answer 22

1. Endocytosis and import
2. Phosphatidyl Choline, leaves Ceramide (FA and sphingosine)
3. Ceraminidase releases sphingosine and FA (Sphingosine inhibs PKC, ceramides involved in stress response)

Question 23

Niemann Pick

Answer 23

AR, resist to TB
Defect in sphingomyelin Degrade. Can’t remodel membrane. A (hepatosplenic accumulation; neurodegen leading to death) B(no neural; spleen, liver, marrow affected)

Question 24

Gm1 gangliosidosis

Answer 24

Defect in beta-galactosidase. Accumulation of GM1 and keraten sulfate. Neurodegen, hepatosplenomegaly, skl deform, cherry red macula

Question 25

Tay Sachs

Answer 25

Defect in beta-hexosominidase A. Accumulate GM2. Rapid neuro degen, blind, cherry red macula, muscle weakness, seizures

Question 26

Sadhoff's disease

Answer 26

Defect in B-hexosaminidase A and B. Accum GM2 and globosides. Sym of Tay sachs but with visceral involvement

Question 27

Fabry Disease

Answer 27

Defect in alpha-galactosidase. Accum of globosides. Red purp rash, kid and heart fail, burning in lower extremities

Question 28

Gaucher Disease

Answer 28

Defect in Beta-glucosidase. Accum of glucocerobosides. Most common lysosomal storage disease, hepatosplenomegaly, osteoporosis.

Question 29

Farber Disease

Answer 29

Defect in Ceraminidase. Accum of Ceramide. Joint deform, hoarse cry, granulomas