10/19 Synthesis of Cholesterol Flashcards
cholesterol in chylomicrons
regular cholesterol in membrane, cholesterol esters inside
cholesterol is an obligate precursor for (3)
bile salts
hormones
vitamin D
which cells synthesize the most cholesterol
hepatocytes
which 5 tissues make more than avg cholesterol
liver adrenal glands gonads enterocytes glial cells (oligodendrocytes and astrocytes)
sources of acetyl CoA
Brain: pyruvate from glycolysis
Other tissues: FA B-oxidation and pyruvate from glycolysis
how does Acetyl CoA get from mitochondria to cytosol
citrate-malate-pyruvate shuttle
name of the transporter of citrate across inner mitochondrial membrane
SLC25A1
passive diffusion across outer membrane
how does pyruvate become citrate in the matrix
2 pyruvate –> oxaloacetate –(plus Acetyl CoA)–> citrate
what enzyme ligates 2 pyruvate into oxaloacetate, location
matrix
pyruvate dehydrogenase
what cytosolic enzyme makes Acetyl CoA from citrate
ATP-citrate lyase (makes oxaloacetate, byproduct is Acetly CoA)
rate limiting enzyme of cholesterol synthesis
HMG-CoA reductase
three ways to regulate HMG-CoA reductase
statins (comp inhibition)
feedback inhibition (cholesterol is allosteric inhibitor)
transcription (when cytostolic cholesterol is low, SREBP enters nucleus and ^ transcription)
what drug targets bone degredation diseases
bisphosphonates
target the farnesyl pyrophosphate synthase enzyme, lower cytosolic farnesyl-PP and geranyl-PP
rebalances osteoblasts and osteoclasts
consequence of a 3 B hydroxysteroid dehydrogenase deficiency
inhibits all downstream pathways, so almost no glucocorticoids, mineralocorticoids, testosterone, progesterone, or estrogen
consequences of a 17 a-hydroxylase deficiency
no cortisol or sex hormones produced (no estradiol or testosterone in F). progesterone is diverted to produce mineralocorticoids so you get excess aldosterone –> HTN
what two molecules can be added to primary bile acids to make them conjugated bile acids
taurine and glycine
what are the two primary bile acids
cholic acid and chenodeoxycholic acid
what happens to conjugated bile acids
bile canaliculi
bile duct system
major duodenal papilla (or gall bladder)
2nd pt of duodenum [gut flora makes them secondary bile acids]
how are bile salts recycled
hepatic portal veing takes them up from the ileum and returns them to the liver, saves E req’d for de novo synthesis
what causes gall stones
imbalance of cholesterol and bile salts, can be caused by fibrates
CF: pain in ULQ after fatty meal
three steps of steroid hormone synthesis
- transport of cholesterol into mitochondria
- cholesterol —> pregnenolone (to SER)
- in SER, special processing depending on tissue location
what enzyme transports cholesterol across the outer mitochondrial membrane
StAR
steroid acute regulatory protein
what enzyme turns cholesterol into pregnenolone
P450scc
side chain cleaving
layers of the adrenal glands, from outer to inner
zona glomerulosa
zona fasiculata
zona reticularis
adrenal medulla
