Membrane Lipids Flashcards
lipids and cancer
- cancerous cells need to make a lot of membrane lipid in order to divide rapidly
- upregulate citratelyase and down regulate FA oxidation
sphingosine 1 phosphate
contributes to cancer and inflammation
-crohns, ulcerative colitis
lysosomal storage diseases
-can not break down sphingolipids due to genetic disorders of metabolism
different scaffolds
- glycerol
- sphingosine
glycerophospholipids
- 2 FAs in ester linkages as positions 1 and 2
- head group in a phosphodiester linkage at position 3
head groups
- serine
- choline
- ethanolamine
- glycerol
- inositol
cardiolipin
- double phospholipid
- exclusive to the inner membrane of the mitochondria
what do fatt acid salts form
- micelles
- individual units are wedge shpaed with a carboxylic head and an aliphatic tail
phospholipids form
- membrane bilayers
- individual units are cylindrical
- glycerophospholipids will spontaneously form bilayers in awueous solution
flip flopping of membrane lipids
- very unlikely to happen spontaneously
- the enzyme flippase is required
- this has implications in membrane properties such as in RBC’s (PC on outer and PE and PS on inner)
common lecithin
- 1 stearoyl, 2 oleoyl-phosphatidyl choline
- most abundant human membrane lipid
- unsaturated FA on C2 lowers melting point creating a fluid membrane
lung sufractant
- 1,2 palmytoil-phosphatidyl choline
- reduced fluidity important for coating air-water interface, preventing alveolar collapse
- deficiency can lead to respiratory distress syndrome in premature infants
what does the formation of glycerophospholipids start with?
PA or DAG
general mechanism for head group addition
- CDP activation of one hydroxyl by adding phosphate via kinase then CTP via cytidyltransferase
- second hydroxyl displaces CMP to give phosphodiester
starting reactants to make ethanolamine or choline
-start with a head group activated with CDP then add diacylglycerol
starting reactants for making inositol (PI), glycerol, or PGC3 (cardiolipin)
-start with diacylglycerol activated with CDP then add a head group
glycerophospholipid interconversion
- SAM (S-adenosyl methionine) is used as a methyl donor in several processes
- only way to form PS is to convert it from PE
plasmalogens
- glycerophospholipids with fatty alcohol in ether linkage at C1
- activated platelet secretion and alters membrane permeability
- abundant plasmalogens in mitochondrial inner membrane may resist oxidative damage that would hydrolyze the ester bonds in normal PL’s
phospholipases
- PLA2 release PUFAs acted upon by oxygenases to make intracellular signaling molecules
- PLAs rearrange FA’s
- PLA’s are found in many venoms
modified FA’s as intracellular signals
- certain stresses induce phospholipase A to release long chin PUFAs from membrane phopholipids
- eicosanoids
cyclooxygenase
phospholipase
- gives rise to prostaglandins and thromboxanes which act as short range intracellular signals
- removes 2 double bonds, subscript shows number remaining
lipoxygenases (phospholipase)
- generate leukotrienes
- important for the immune response
- number of double bonds is unchanged
- modulate cellular chemotaxis, cytokine release
- mediate vascular permeability and bronchioconstriction
DAG
- second messenger
- activates PKC
IP3
- causes release of Ca2+
- activates calmodulin kinase
- promotes growth and development
what are DAG and IP3 released from
- PIP
- extracellular signal binds membrane spanning receptor to activate PLC which cleaves PIP into IP3 and DAG
sphingolipids
- membrane lipids not based on glycerol
- based on sphingosine
- common membrane component in myelin sheath, sphingolyelin with C24 FA’s provides electrical insulation
multiple myeloma
-auto immune disease where you lose myelination in the CNS
types of glycolipid, what is theur classification
- sulfatides
- globosides
- gangliosides (charged, neuraminic acid)
- these are a type of sphingolipid
- glucose added as UDP glucose or UDP galactose
blood grouping antigens
- these are gangliosides and globosides
- they are markers in cellular recognition
normal sphingolipid breakdown pathways
- membrane lipids are constantly pulled from the surface into endosomes
- some are reused others are broken down in lysosomes and their components recylcled
- each sugar linkage in the glycosphingolipids (cerebrosides, globosides, and gangliosides) requires a seperate enzyems for removal
