phospholipids Flashcards
2 main classes of phospholipids
- glycerophospholipids (glycerol backbone)
- sphingolipids (sphingosine backbone)
4 components of glycerophospholipid
backbone- glycerol
Head group- variable, esterified via OH to PO4
FA1- saturated (palpitate or stearate)
FA2- unsaturated (arachidonic acid)
where is the site of glycerophospholipid synthesis? how distributed in cell?
cytosolic face of ER, following synthesis will travel to golgi for distribution
what is the simplest glycerophospholipid?
phosphatidic acid (head group = H)
what results when FA1 or FA2 are removed from a glycerophospholipid?
lysophosphoglyceride
what are the functions of lysophosphoglyceride in the cell?
signaling or pro-inflammatory
what are the sources of glycerol-3-p?
- from DHAP (liver and adipose)
- free glycerol phosphorylated by glycerol kinase (liver only)
in the synthesis of phosphatidic acid, what is the required activator of the polar head group and hydrophobic tail?
CTP (cytidylyl triphosphate)
phosphatidic acid is the precursor for the synthesis of what 2 things?
- glycerophospholipids
- triglycerides
what is the only antigenic human phospholipid?
cardiolipin
what is the structure of cardiolipin?
2 molecules of esterified phosphatidic acid
where is cardiolipin found?
inner mito membrane
bacterial membranes
what is the physiologic role of cardolipin in the mitochondria?
cardiolipin contains an ionized “bridge” that acts as a buffer to trap H+ in the inner mito membrane and maintain electron flux in the ETC
what is the action of cardiolipin oxygenate? consequences?
cardiolipin oxygenase causes per oxidation of unsaturated acyl chains on cardiolipin, triggers apoptosis
describe apoptosis caused by cardiolipin peroxidation
when cardiolipin in peroxidized, a large pore forms in the inner mito membrane that allows for the passage of cytochome C into the cytosol, while in the cytosol, cytochome C binds IP3 to trigger Ca release from SER that induces more cytochrome c movement into cytosol
2 types of ether phospholipids
- alkyl (saturated)
- alkenyl (unsaturated)
2 biologically important alkenyl ether phospholipids
- ethanolamine plasmogen (in myelin)
- choline plasmogen (in heart mm)
main phospholipid component of PAF?
phosphatidylcholine
2 reactions mediated by PAF
1- acute inflammation
2- anaphylactic shock
what cells are acted on by PAF to produce inflammation/anaphylaxis?
- neutrophils/macrophages = superoxide anions
- platelets = aggregation and degranulation
how does PAF affect the cell membrane?
will bind to external PAF receptor, activate transmembrane signaling domain that will trigger phospholipases = phospholipid degradation
main phospholipid component of surfactant
dipalmitoylphosphatidylcholine
cells that produce surfactant
type II granular pneumocytes
purposes of surfactant (3)
- decrease alveolar surface tension
- prevent alveolar collapse
- reduce susceptibility for free radial oxidation
RDS/hyaline membrane disease
in premature infants due to inadequate lung maturity at birth, assess risk with phos-choline:sphingomyelin ratio
respiratory failure related to surfactant
in adults, caused by damage to type II pneumocytes, commonly asdic with immunosuppressive medication or chemotherapy
how is phosphatidylserine synthesized?
from phosphatidylethanolamine: serine is exchanged for free serine
how is phosphatidylcholine synthesized from phosphatidylserine in the membrane?
- Phos-serine is decarboxylated to phos-ethanolamine
- PE undergoes 3 successive methylations (donor = SAM)
- Phos-choline formed
after SAM donates methyl group, what is formed?
SAH (s-adenosylhomocysteine)
what is SAM?
s-adenosylmethionine
what limits the ability to perform de novo synthesis of phos-choline?
availability of methionine
essential aa, often deficient in diet
besides de novo synthesis, what is another way that cells can make phis-choline?
using the salvage pathway (CDP-choline pathway) that will activate free choline for reincorporation into lipid membranes
choline sources (3)
- synthesis in the liver
- dietary intake (meats, eggs, some veggies)
- recycling (Phos-choline, sphingomyelin, ACH)- using salvage pathway
what can result from deficiency of choline?
impairment of brain development and memory
general type of enzyme that degrades glycerophospholipids
phospholipases
phospholipase A1
removes FA from sn1 position
phospholipase A2
removes FA from sn2 position to yield free FA + lysophospholipid; release arachidonic acid that is used for eicosanoid synthesis and removes damaged PUFA from membrane
phospholipase C
cleaves phosphodiester bond between C3 and phosphate
phospholipase D
cleaves phosphodiester bond between phosphate and polar head group
4 types of phospholipase A2
1- cytosolic
2- Ca-independent intracellular
3- secretory
4- pancreatin
cytosolic phospholipase A2
activated by increased Ca and by phosphorylation by MAP kinase, will release arachidonic acid for eicosanoid synthesis
calcium independent intracellular A2
involved in turnover and remodeling of phospholipids
secretory A2
active extracellularly, role in sepsis and inflammation
pancreatic A2
digestive enzyme, released as zymogen
3 components of sphingolipids
- backbone= sphingosine
- one fatty acid- usually saturated
- polar head group
what is the polar head group in sphingomyelin?
choline
ABO group determinants are:
sphingolipids (specifically glycolipids)
what is ceramide?
a sphingolipids that is a 2nd messenger and is important for cell differentiation or apoptosis
what is the result of interaction between cholesterol and sphingomyelin in the cell membrane?
assoc with cholesterol promotes the transition from gel phase to liquid state
what are the membrane domains assoc with sphingolipids?
caveolae and lipid rafts
what enzyme will degrade sphingolipids?
sphingomyelinase
what disease has a deficiency of sphingomyelinase?
Niemann-Pick type 1
what are the sx of niemann-pick type 1?
enlarged liver and spleen due to accumulation of lipids, mental retardation, death in childhood
what are glycolipids?
sphingolipids with sugar as the polar head group
2 types of glycolipids
- cerebroside- ceramide + one sugar
- ganglioside- ceramide + branched sugar
