Membrane Lipids Flashcards
Amphipathic
- Hydrophilic head group
- hydrophobic FA tails
- Bilayer forms with tails pointing in and heads out interacting w/ H2O
Major Phospholipids w/ Function
- Phosphatydic Acid: major constituents of cell membranes
- Phosphatidylethanolamine : nervous tissue such as the white matter of brain, nerves, neural tissue, and in spinal cord,
- Phosphatidylcholine: found in the exoplasmic or outer leaflet of a cell membrane.
- Phosphatidylserine: inner-leaflet of cell membranes
- Phosphatidylinositol: Roles in lipid signaling, cell signaling and membrane trafficking
- Cardiolipin: Regulates aggregate structures
- Phosphatidylglycerol: found in pulmonary surfactant
Phosphatidic Acid Synthesis
- Glycerol–>glycerol-3-phosphate
* Mediated by glycerol kinase
* uses ATP- G3P–>phosphatidic acid
- acyl transferase
- Req FA binding protein
- G3P–>phosphatidic acid
Phosphatidylcholine Synthesis
- CTP activates choline head group:
- CTP+choline–>CDP-choline
- cytidyl transferase
- Phosphatidic acid–>diacylglycerol (DAG)
- Phosphatidic acid phosphatase (P cleaved)
- DAG+CDP-choline–>phosphatidylcholine
- Also formed from PE:
- phosphatidylethanolamine methyltransferase (PEMT)
- Converts PE to PC by sequential methylation in liver
- Req S adenocyl methionine
Phosphatidylethanolamine Synthesis
- CTP activates ethanolamine head group:
- CTP+ethanolamine–>CDP-ethanolamine
- cytidyl transferase
- Phosphatidic acid–>diacylglycerol (DAG)
- Phosphatidic acid phosphatase (P cleaved)
- DAG+CDP-ethanolamine–> phosphatidylethanolamine
- Also produced by conversion from Phosphatidylserine
- PS decarboylase
- Releases CO2
Phosphatidylserine Synthesis
- CTP activates serine head group:
- CTP+serine–>CDP-serine
- cytidyl transferase
- Phosphatidic acid–>diacylglycerol (DAG)
- Phosphatidic acid phosphatase (P cleaved)
- DAG+CDP-serine–> phosphatidylserine
- Also produced by conversion from PE:
- PS synthase converts the 2 head groups
Phosphatidylinositol Synthesis
- Phosphatidic acid activated by CTP
- PA+CTP–>CDP-DAG
- transferase
- Releases PPi
- Inositol head group added
- CMP released
- PI synthase
Cardiolipin Synthesis
- Phosphatidic acid activated by CTP
- PA+CTP–>CDP-DAG
- transferase
- Releases PPi
- PG head group added
- nucleophilic attack by PG on PA
Phophatidylglycerol Synthesis
- Phosphatidic acid activated by CTP
- PA+CTP–>CDP-DAG
- transferase
- Releases PPi
- glycerol head group added
- CMP released
- PG synthase
Location of Membrane lipid synthesis
-Cytosolic face of ER
_Except for plasmalogens (ether glycerlipids) they are synthesized in peroxisome
-
6 fumctions of Phospholipids
- Converted to arachidonic acid
- Lung surfactant
- Blood lipoproteins
- Membranes
- Bile
- Platelet activation
Major components of Membranes
- Fxn to sperate cytosol from extacellular space
- Outer leaflet: PC, sphingomyelin
- Inner leaflet: PE, PS, PI
- intracellular compartmentalization
- Affects fluidity
- Saturated FA are very tight and rigid
- Unsaturated FA increase fluidity
- Cholesterol increases fluidity by interfering w. lipid packing
Precursors to signaling Molecules
- Arachidonic Acid: Eicosanoids
- PA: activate kinases
- Sphingosine: angiogenesis
- Isoprostanes: From free radical peroxidation of AA
- inflammatory mediators
Emulsifiers
-Phospholipids promote bile function
-dispersion of tiacylglycerols and cholesterol esters
Solubilize cholesterol in bile
-Critical components of lipoproteins
*Transport cholesterol in circulation
Lung Surfactant
- Type II alveolar cells produce surfactant
- Reduces surface tension and lowers pressure required to inflate alveoli
Ether glycerolipids (2)
- Plamologens
2. Platelet activating factor
Sphingophospholipids (1)
- Sphingomyelin
Glycolipids (4)
- Cerebrosides
- Sulfatides
- Globosides
- Gangliosides
Plasmalogen Syntheseis
- DHAP+FA-CoA–>1-acyl-DHAP
-DHAP acyltransferase
2.Replace FA w/ROH forming ether linkage
_Alkyl DHAP synthase - Reduces C2 ketone to alcohol
- Add fatty acid to the alcohol
- Dephosphorylation
- Reacts w/ activated head groups
-CDP-ethalamine or CDP-choline
7.Desaturation of FA using NADPH and O2
-forms final plasmalogen
Functions of Plasmalogens (3)
- Ethanolamine plasmalogen found in myelin
- Choline plasmalogen in heart muscle
- Platelet activating factor fxn in platelet aggregation and inflammation
- formed from remodeling
Platelet Activating Factor
- Synthesized in response to stimulation
- Glycerphosphocholin releases FA
- Forms Lyso-PAF:
- Acetyltransferase forms final PAF
- Function: kinase activation
- inflammation modulation
Shingolipids
- backbone from serine
- FA and head group
- Ceramide: Backbone+FA amide
Ceramide Synthesis
- Serine+palmitoyl CoA
- Serine decarboylated & displaces CoA
- Reduction of ketone to alcohol
- Uses NADPH
- forms dihydroshingosine
- Addition of FA group
- forms N-FA derivative
- Oxidation of FA using FAD
- Forms ceramide
Sphingomyelin Synthesis
- Ceramide+PC–>Sphengomyelin
- DAG released
- Insulates and protects nerve axons
- Ensures rapid signal transmission
Sulfatide Synthesis
- Ceramide+UDP-galactose–> galactocerbroside
- Sulfate transferase adds sulfate group to glactose
- Major brain sulfolipid
Globoside Synthesis
- Ceramide+UDP-Glucose–> glucocerebroside
2. Galactose added by UDP-Gal
Ganglioside Synthesis
- Ceramide+UDP-Glucose–> glucocerebroside
- Addition of UDP-sugars
- CMP-NANA added to Gal
- Negatively charged ceramide oligosaccharides
Phospholipases
PLA1: hydrolyzes ester at position 1
PLA2: releases FA w/ ester hydrolysis @ FA2
PLC: Hydrolyzes phosphate forming DAG
PLC: hydrolyzes phosphate forming PA
Sphingolipids in V. Cholerae
- toxin effects mediated by interaction w/ GM1 gangliosides on intestinal mucosa cells
- toxin ribosylate G-alpha and increases cAMP causing water loss and diarrhea
Flu Transmission
- Viral nuraminidase cleaves NANA from cell receptor
- allows release of virus particles
- Nuraminidase inhibitors halt spread of infection
Niemann Pick
- accumulation of sphingomyelin in brain & blood cells
- sphingomyelinase deficiency
- MR, spasticity, seizures, ataxia, death by age 2-3
- Autosomal Recessive
Fabry Disease
- accumulation of glycolipids in brain, heart, kidney
- alpha galactosidase A deficiency
- pain in extremities, skin lesions, ischemic infarction of kidney, brain, heart
Krabbe disease
-accumulation of glycolipids destroying oligodendrocytes
-beta galactosidase deficiency
-demyelination: spasiticty & neurodegeneration leading to death
Hypotonia, hyperreflexia, blind, deaf
Gaucher disease
- accumulation of glucocerebrosides in blood, liver, spleen
- glucocerebrosidase deficiency
- hepatosplenomegaly, anemia, thrombocytopenia, bone pain, femur deformity
Tay-Sachs disease
- accumulation of GM2 gangliosides in neurons
- Hexosaminidase A deficiency
- Progressive neurodegeneration, developmental delay, death
