Cholesterol Metabolism Flashcards
cholesterol purpose
maintains cell membrane
makes steroid hormones, bile acids, and vitamin D
cholesterol synthesis aka
mevalonate pathway
cholesterol synthesis location
smooth endoplasmic reticulum
cholesterol synthesis step 1
2 acetyl-CoA to acetoacetyl-Coa
enzyme: thiolase
releases CoASH
cholesterol synthesis step 2
acetoacetyl-Coa to HMG-Coa + free CoA
enzyme: HMG-CoA synthase
acetyl-CoA becomes CoASH
cholesterol synthesis step 3
HMG-CoA to mevalonate
enzyme: HMG-CoA reductase
2 NADPH +2 H+ to 2 NADP+
releases CoA-SH and H2O
rate limiting step of cholesterol synthesis
HMG-CoA reductase step
cholesterol synthesis step 4
mevalonate to 5-pyrophosphomevalonate
enzyme: mevalonate kinase AND phosphomevalonate kinase
Each one turns 1 ATP to 1 ADP
Activation of mevalonate!
cholesterol synthesis step 5
5-pyrophosphomevalonate to isopentenyl pyrophosphate
enzyme: Enzyme: pyrophosphomevalonate decarboxylase
ATP + H2O to ADP + Pi + CO2
After step 5
isopentenyl pyrophosphate eventually becomes 2 farnesyl pyrophosphate (15 Carbons), then squalene (30 Carbons)
What happens to squalene?
squalene is cyclized to cholesterol
oxygen is being reduced, lots of electron carriers being reduced, lots of energy used
where is majority of cholesterol made and used?
the liver!
makes bile acids
where are bile acids stored?
bile acids stored in gallbladder and released into intestine when need during digestion for fat digestion
how does cholesterol move through the bloodstream?
it needs lipoproteins bc it is insoluble in water
lipoproteins
part lipophilic and part hydrophilic
can all cells make cholesterol?
yes, they can all make it for themselves
what other organs use cholesterol?
adrenal glands and gonads use cholesterol to make steroid hormones
where are isoprenes used?
all over: lots of uses
when do we want to turn off the cholesterol pathway?
never!
what type of molecule is farnesyl pyrophosphate?
a polyisoprene
how is farnesyl pyrophosphate used?
lipids links for proteins
tail for ubiquinone
modified nucleotides
methods of cholesterol regulation
1) HMG-CoA reductase
2) allosteric effects by covalent modification
HMG-CoA reductase control
short-term: by energy competitors, allosteric binding and hormone effects
long-term: synthesis and degradation
HMG-CoA reductase kinase aka
AMPK
HMG-CoA reductase is active when
it is not phosphorylated
HMG-CoA reductase is inactive when
it is phosphorylated
Low energy leads to
decreased HMG-CoA reductase and decreased cholesterol synthesis
AMPK is activated by
high AMP aka low ATP and low energy
what enhances effect of energy regulation?
presence of cAMP
what does cAMP do
decreases phosphatase activity which decreasing activating activity of AMPK
in low energy,
liver won’t synthesize cholesterol
in high energy,
liver will synthesize cholesterol
HMG-CoA reductase levels
Cholesterol in LDL and mevalonate control the synthesis and degradation of the enzyme resulting in changes of up to 200-fold
what can we make from cholesterol?
1) steroid hormones
2) vitamin D (in the presence of UV light)
3) bile acids/bile salts
