B4 lipids Flashcards
what is the structure of a phospholipid
2 fatty acids joined to a glycerol mol with a phosphate and an alcohol tail
phosphatidylinositol (P1)
precursor of signalling mols
phosphatidylserine (P2)
a key eat me signal in apoptosis
phosphatidylcholine (PC)
structural component of membranes
phosphatidylethanolamine (PE)
donor of functional groups to some membrane anchored proteins; structural roles, regulates curvature
sphingomyelin
parent sphingolipid
a precursor of some signalling mols, involved in lipid rafts
cholesterol
can be as much as % of membrane lipid
key in regulating fluidity and permeability
involved in lipid rafts
each glycerophospholipid is a class with variations in what side chains
fatty acyl
fatty acids can be saturated or saturated
what does this mean
saturated (no double bonds)
unsaturated (double bonds)
how many Cs long is a fatty acid
12-22
lipids are amphipathic
what does this mean
have both hydrophobic and philic regions
in this case a hydrophobic tail and a polar head group
what does it mean for a membrane to be described as fluid
they accommodate protein conformational changes without loss of integrity
certain signals catalyse the breakdwon of Ptdlns (4,5)P2 into what
inositol triphosphate and diacylglycerol
both are key intracellular messengers
GPL biosynthesis is via what pathway and where
phosphatidate and within the ER
what is de novo glycerophospholip synthesis
combination of activated alcohol (headgroup) with diacylglycerol
what cellular lipid is a major component of lung surfactant
PC
what does PC normally maintain
surface tension of fluid to keep alveoli open
what does low PC result in
collapse of alveoli
what is respiratory distress syndrome and who does it affect
often premature babies
laboured breathing blue fingers/toes
how is respiratory distress syndrome treated
ventilation (O2) and artificial surfactant
what is ceramide
precursor for sphingomyelin (the major sphingolipid
what is ceramide synthesised from
synthesised from serine and palmitoyl-CoA
how are sphingolipids further modified
addition of sugars
what are gangliosides
important in cell surface mols
highly prevalent in nervous tissue
what is a disease involving gangliosides
tay sachs disease
what does tay sachs disease involve
an inherited disorder
affects motor function, then vision, fatal by 3 years
can be diagnosed during pregnancy
no treatment available
what causes tay sachs disease
inability to degrade gangliosides
(normally happens in lysosomes)
lysosomes (esp in neurons) fill with gangliosides
what is sphingosine phosphorylated by and what does it produce
by sphingosine kinase
generating sphingosone 1-phosphate
a key signalling mol
what is cholesterol
an essential component of membranes
helps maintain membrane bilayer integrity and regulates permeability
what is cholesterol a precursor of
steriods, vitamins, and bile salts
what is excess cholesterol associated with
cardiovascular disease
what does cholesterol biosynthesis use
acetyl CoA
3 steps of cholesterol biosynthesis
- synthesis of isopentyl pyrophosphate (via mevalonate) the building block of cholesterol
- condensation of 6 mols of isopentyl pyrophosphate to form squalene
- cyclisation of squalene and further processing to cholesterol
how much does the rate of cholesterol synthesis vary and what is it dependent on
700 fold
depending on how much is in the diet
the rate of synthesis is responsive to how much cellular cholesterol is present
what is this mechanism
feedback regulation
what is the major site of cholesterol synthesis
and site of significant synthesis
liver
intestines
what regulates cholesterol synthesis
HMG-CoA reductase
(integral membrane protein in the ER)
how does HMG-CoA reductase regulate cholesterol synthesis
catalyses the committed step of cholesterol synthesis
its amount
its activity
what are the 4 ways in which HMG-CoA reductase is controlled
-rate of synthesis of HMG-CoA reductase mRNA
-rate of translation of HMG-CoA reductase mRNA to protein
-rate of degradation of HMG-CoA reductase protein
-phosphorylation state of HMG-CoA reductase protein
what transcription factor is used in the transcriptional regulation of HMG-CoA reductase
SREBP
sterol regulatory element binding protein
what is SRE (sterol regulatory element) in transcriptional regulation of HMG-CoA reductase
region of HMG-Coa reductase gene to which DNA binding domain of SREBP binds
what is the rate of translation of HMG-CoA reductase mRNA to protein inhibited by
nonsterol metabolites derived from mevalonate
what senses increasing levels of sterols
HMG-CoA reductase membrane domain
after increasing levels of sterols have been detected the membrane domain indirectly acts with what and what is the result
ubiquitinating enzymes
HMG CoA reductase becomes polyubiquitinated
after HMGCoA red becomes polyubiquitinated what happens
is extracted from membrane and degraded by the proteasome
what does phosphorylation do to the catalytic activity of HMGCoA red
decreases
what is phosphorylation carried out by in regulation of HMG CoA reductase
AMP activated protein kinase
what does phosphorylation of HMG-CoA red do to cholesterol synthesis
stops it
how is cholesterol transported throughout the body and their structure
in body fluids in lipoprotein particles
hydrophobic lipid core, surrounded by polar lipids and proteins
what is the good cholesterol
HDL (high density lipoprotein
what is the bad cholesterol
LDL (low density lipoprotein)
what are bile salts, where are they synthesised and stored
-detergents (solubilise dietary lipids)
-synthesised in liver
-stored in gall bladder and released into small intestine
what are the 5 classes of steroid hormones
-progestagens
-glucocorticoids
-mineralcorticoids
-androgens
-oestogens
what are statins
HMG-CoA reductase inhibitors
act as lipid lowering drugs to reduce cholesterol
when are statins prescribed
if patient has at least one risk factor for coronary heart disease
what are the 3 statins regularly prescribed
atorvastatin
fluvastatin
lovastatin
