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Block 4 MBOD > 10/19 Synthesis of Cholesterol > Flashcards

10/19 Synthesis of Cholesterol Flashcards

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1
Q

cholesterol in chylomicrons

A

regular cholesterol in membrane, cholesterol esters inside

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2
Q

cholesterol is an obligate precursor for (3)

A

bile salts
hormones
vitamin D

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3
Q

which cells synthesize the most cholesterol

A

hepatocytes

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4
Q

which 5 tissues make more than avg cholesterol

A 
liver
adrenal glands
gonads
enterocytes
glial cells (oligodendrocytes and astrocytes)
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5
Q

sources of acetyl CoA

A

Brain: pyruvate from glycolysis

Other tissues: FA B-oxidation and pyruvate from glycolysis

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6
Q

how does Acetyl CoA get from mitochondria to cytosol

A

citrate-malate-pyruvate shuttle

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7
Q

name of the transporter of citrate across inner mitochondrial membrane

A

SLC25A1

passive diffusion across outer membrane

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8
Q

how does pyruvate become citrate in the matrix

A

2 pyruvate –> oxaloacetate –(plus Acetyl CoA)–> citrate

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9
Q

what enzyme ligates 2 pyruvate into oxaloacetate, location

A

matrix

pyruvate dehydrogenase

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10
Q

what cytosolic enzyme makes Acetyl CoA from citrate

A

ATP-citrate lyase (makes oxaloacetate, byproduct is Acetly CoA)

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11
Q

rate limiting enzyme of cholesterol synthesis

A

HMG-CoA reductase

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12
Q

three ways to regulate HMG-CoA reductase

A

statins (comp inhibition)
feedback inhibition (cholesterol is allosteric inhibitor)
transcription (when cytostolic cholesterol is low, SREBP enters nucleus and ^ transcription)

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13
Q

what drug targets bone degredation diseases

A

bisphosphonates
target the farnesyl pyrophosphate synthase enzyme, lower cytosolic farnesyl-PP and geranyl-PP
rebalances osteoblasts and osteoclasts

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14
Q

consequence of a 3 B hydroxysteroid dehydrogenase deficiency

A

inhibits all downstream pathways, so almost no glucocorticoids, mineralocorticoids, testosterone, progesterone, or estrogen

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15
Q

consequences of a 17 a-hydroxylase deficiency

A

no cortisol or sex hormones produced (no estradiol or testosterone in F). progesterone is diverted to produce mineralocorticoids so you get excess aldosterone –> HTN

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16
Q

what two molecules can be added to primary bile acids to make them conjugated bile acids

A

taurine and glycine

17
Q

what are the two primary bile acids

A

cholic acid and chenodeoxycholic acid

18
Q

what happens to conjugated bile acids

A

bile canaliculi
bile duct system
major duodenal papilla (or gall bladder)
2nd pt of duodenum [gut flora makes them secondary bile acids]

19
Q

how are bile salts recycled

A

hepatic portal veing takes them up from the ileum and returns them to the liver, saves E req’d for de novo synthesis

20
Q

what causes gall stones

A

imbalance of cholesterol and bile salts, can be caused by fibrates
CF: pain in ULQ after fatty meal

21
Q

three steps of steroid hormone synthesis

A
  1. transport of cholesterol into mitochondria
  2. cholesterol —> pregnenolone (to SER)
  3. in SER, special processing depending on tissue location
22
Q

what enzyme transports cholesterol across the outer mitochondrial membrane

A

StAR

steroid acute regulatory protein

23
Q

what enzyme turns cholesterol into pregnenolone

A

P450scc

side chain cleaving

24
Q

layers of the adrenal glands, from outer to inner

A

zona glomerulosa
zona fasiculata
zona reticularis
adrenal medulla

25
Q

what hormone is produced by the zona glomerulosa

A

mineralocorticoids (aldosterone)

stim Na2+ reabsorbtion –> H2O retention

26
Q

what hormone is produced by the zona fasiculata

A

glucocorticoids (cortisol)

stress response, affects metabolic fxns, anti-inflammatory, decreases immune response

27
Q

what hormone is produced by the zona reticularis

A

androgens (weak activity)

28
Q

what molecule marks the divergence in sex hormone synthesis between M and F

A

androstenedione

29
Q

enzyme to make most active male sex hormone

A

5 a-reductase

testosterone –> dihydroxytestosterone

30
Q

enzyme to make most active female sex hormone

A 
aromatase (testosterone -->estradiol)
17 hydroxylase (estrone -->estradiol)

Block 4 MBOD (6 decks)

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