Cholesterol Biosynthesis Flashcards

1
Q

cholesterol solubility in water

A
  • low solubility in water
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2
Q

cholesterol present in plasma bound to

A
  • lipoproteins
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3
Q

cholesterol esters are located where

A
  • in the interior of lipoproteins
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4
Q

free cholesterol is located where

A
  • on the surface of lipoproteins
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5
Q

cholesterol is a precursor for

A
  • bile acids
  • steroid hormones
  • vitamin D
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6
Q

result of defects in cholesterol synthesis in mice

A
  • generally lethal
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7
Q

most cholesterol synthesis occurs where?

A
  • in the liver

- 80%

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8
Q

what is cholesterol synthesized from

A
  • HMG CoA in the cytosol
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9
Q

rate limiting step of cholesterol synthesis

A
  • HMG CoA reductase
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10
Q

role of insulin in cholesterol synthesis

A
  • positive regulator of HMG CoA reductase
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11
Q

important intermediates in cholesterol synthesis

A
  • geranyl diphosphate

- farnesyl diphosphate

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12
Q

geranyl diphosphate goes on to to create

A
  • geranylgeranyl disphosphate
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13
Q

geranylgeranyl diphosphate goes on to create

A
  • ubiquinone

- geranylgeranylated proteins (rho)

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14
Q

ubiquionine important for

A
  • oxidative phosphorylation
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15
Q

geranylgeranylated proteins important for

A
  • signal transduction
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16
Q

fernesyl diphosphate goes on to create

A
  • fernesylated proteins (Ras)

- dolichol phosphate

17
Q

dolichol phosphate important for

A
  • synthesis of complex glycoproteins
18
Q

HMGCoA reductase expression and activity inhibited by

A
  • oxysterols derived from intracellular free cholesterol
19
Q

LDL receptors are down regulated by

A
  • free cholesterol
20
Q

fat and cholesterol are made in what state?

why

A
  • in the fed state

- it takes 18 ATP to make them

21
Q

mechanisms to control cellular cholesterol levels

A
  • biosynthesis
  • uptake
  • catabolism & excretion
  • storage
22
Q

uptake

A
  • LDL receptors on liver allow cholesterol to be taken up
23
Q

storage

A
  • liver stores cholesterol using ACAT
24
Q

diet high in cholesterol result

A
  • too much cholesterol in cell
  • negative feedback on LDL receptors
  • more cholesterol in the circulation
25
Q

diet high in saturated fats

A
  • inhibit storage of cholesterol
  • more cholesterol in cell
  • down regulation of LDL receptors
  • more cholesterol in circulation
26
Q

result of saturated fatty acids

A
  • reduce membrane fluidity

- reduce clustering and uptake of LDLR

27
Q

diet low in fiber

A
  • not secreting bile acids out of system
  • higher level of cholesterol inside cell
  • down regulation of LDL receptors
  • up regulation of plasma LDL
28
Q

primary bile acids are synthesized where

A
  • in the liver
29
Q

rate limiting step for bile acid synthesis

A
  • 7 alpha hydroxylase
30
Q

which are the primary bile acids

A
  • cholic and chenodeoxycholic acids
31
Q

deoxycholic and lithocholic acids are products of

A
  • further metabolism in the intestine
32
Q

which are the must abundant primary bile acids?

A
  • colic acids
33
Q

how do we convert bile acids to bile salts?

A
  • add groups to make it more polar
34
Q

function of bile acids

A
  • emulsify dietary fats for digestion and absorption
  • facilitate absorption of fat soluble vitamin
  • only significant mechanism for eliminating cholesterol from body
  • prevent precipitation of cholesterol out of solution in gall bladder so you don’t get gall stones
35
Q

7 alpha hydroxylase activated by

A
  • cholesterol
36
Q

7 alpha hydroxylase inhibited by

A
  • bile acids
37
Q

importance of enterohepatic circulation of bile acids

A
  • up to 99% of bile acids are reabsorbed, enter the portal circulation, and return to the liver