Synthesis And Transport Of Cholesterol. Synthesis Is Bile Acids, Bile Salts And Steroid Hormones

Front 1

What is the precursor for ketone bodies?

Back 1

acetyl CoA, when in the mitochondria

Front 2

What is acetyl CoA in the cytosol a precursor for?

Back 2

FFA that are fated for TAGs

Front 3

What is the precursor for cholesterol?

Back 3

acetyl CoA

Front 4

Where is cholesterol made? How is it delivered? Is it a fuel in humans? Why or why not?

Back 4

a) liver… b) lipoproteins… c) No, we lack the enzymes to harvet the energy

Front 5

In what state is cholesterol made?

Back 5

Fed

Front 6

Where does the acetyl CoA come from that is fated for cholesterol?

Back 6

Citrate that gets into the cytosol

Front 7

What are bile salts made from?

Back 7

cholesterol byproducts

Front 8

What organs makes cholesterol?

Back 8

liver, adrenal cortex (cortisol) and gonads (for steroids)

Front 9

What reducing agent is used in cholesterol synthesis?

Back 9

NADPH

Front 10

Where ever you see NADPH, what pathway is also present?

Back 10

Pentose pathway

Front 11

What drives the rxns in cholesterol synthesis and thus what regulates cholesterol synthesis?

Back 11

ATP! ATP!

Front 12

What is the first commited intermediate in cholesterol synthesis?

Back 12

Mevalonate

Front 13

Where do statins work in the reduction of cholesterol?

Back 13

Mevalonate

Front 14

Where is cholesterol synthesized?

Back 14

liver/ cytoplasm

Front 15

Describe the cholesterol synthesis pathway

Back 15

a) Acetyl CoA --> acetoacetyl CoA… acectoacetyl CoA --> HMG-CoA (HMG CoA synthase)… b) HMG CoA --> Mevalonate (2 NADPH + HMG CoA reductase)… c) Mevalonate --> isopentenyl pyrophosphate (3 ATP)… IPP >> geranyl PP >> farnesyl PP >> Squalene >> lanosterol >> cholesterol

Front 16

Which HMG CoA, cytosol or Mitochondrial is involved in cholesterol synthesis?

Back 16

Cytosol

Front 17

Where is HMG CoA acted upon by HMG CoA lyase?

Back 17

in ketone synthesis

Front 18

In cholesterol synthesis, what is acting on HMG CoA?

Back 18

HMG CoA reductase

Front 19

What is the first compound commited to cholesterol synthesis?

Back 19

Mevalonate

Front 20

What regulates cholesterol synthesis?

Back 20

ATP and NADPH

Front 21

Where do statin control cholesterol?

Back 21

Mevalonate

Front 22

What effect does a high insulin:glucagon ratio have on HMG CoA reductase?

Back 22

phosphatase will remove phosphate and make it more active

Front 23

How is cholesterol feedback inhibited?

Back 23

by sterols, which activate protein kinase, which phosphorylates HMG CoA reductase and deactivates it.

Front 24

What is the mechanism by which a low ATP:AMP ratio will result in HMG CoA reductase inhibition?

Back 24

Protein Kinase kinase (PKK) is activated by AMP, which will lead to the the phosphorylation HMG CoA

Front 25

What is the key player in transcriptional control of HMG CoA reductase?

Back 25

Steroid responsive element (SREBP), which binds or doesn't bind to DNA

Front 26

Which part of the SREBP is active in migrating to the DNA?

Back 26

the Amino terminal, which are cut off by proteolytic enzymes.

Front 27

What are the 2 ways the amino terminal of the HMG CoA reductase domain controlled?

Back 27

1) rapid degradation… 2) proteolytic enzyme SCAP and S2P (which are positively regulated by sterols)

Front 28

What are some other positive benefits of statins?

Back 28

a) in alzheimer's, it reduces Cholesterol depostion in vasculature and decreases risk for stroke… b) in osteoporosis, it is suspected that the rxn in the pathway reduce bone loss through a complex elimination of downstream intermediates (similar to bisphosphonates which are taken by people to reduce osteoporosis.)

Front 29

What negative aspects are there in statin use?

Back 29

muscle weakness

Front 30

What other products are made that arise from mevalonate that may have a unfavorable side effect?

Back 30

coenzyme Q, dolichol and vitamin D

Front 31

What transports cholesterol synthesized in the liver?

Back 31

VLDL

Front 32

What fate of VLDL can be detrimental?

Back 32

conversion to LDLs which hang around long enough in circulation to oxidized and be taken up by foam cells --> atherosclerosis

Front 33

Why is it that chylomicrons are not a problem with respect atheroslerosis?

Back 33

They don't hang around, they go to the liver and are recycled.

Front 34

What are two positive aspects of HDLs?

Back 34

1) they can swap Apos… 2) they deliver cholesterol in plasma membranes back to the liver… thus reducing periheral cholesterol

Front 35

Why are Apoproteins important?

Back 35

they dictate where lipoproteins dock and what they do in the plasma

Front 36

What is the relationship betweeen the % of apoproteins and the % of TAGs in lipoproteins?

Back 36

it is inversely proportionate

Front 37

Place the lipoproteins in order from greatest % of apoproteins to least.

Back 37

HDL>LDL>IDL>VLDL>chylomicron

Front 38

What is involved in the hydroxylation cholesterol, part-one of making bile salts?

Back 38

1) add hydroxyl using 7-∂-hydroxylase (multiple additions) and requires the oxidation of NADPH.. 2) oxidize the side chain giving it a negative charge (carboxyl group)

Front 39

What inhibits 7-∂-hydroxyase?

Back 39

bile salts and acid… feedback inhibitioin

Front 40

What is the net effect of adding hydroxyl groups to cholesterol in bile synthesis?

Back 40

it makes cholesterol less fatty

Front 41

What is the second part of making bile salts?

Back 41

Conjugating or coupling compounds to the carboxyl group.

Front 42

What is the process of conjugating cholesterol in bile synthesis?

Back 42

1) activate the carboxy group in the form of a CoA derivative… 2) add taurine or glyciine (increase the fraction of the compound that is negatively charged)

Front 43

What is the charge on the polar part of the bile salt?

Back 43

negative

Front 44

Where is the non-polar of the bile salt?

Back 44

rings of the steroid nucleus

Front 45

What is the significance of the low pKa for the conjugated bile salts?

Back 45

it is ionized more at the gut pH ~6

Front 46

What effect does intestiinal flora (bacteria) have on bile salts?

Back 46

a) they deconjugate the bile salt (remove the taurine or glycine) and… b) remove the 7-∂-hydroxyl group.

Front 47

Does this effect the bodies ability to use the bile salt?

Back 47

no

Front 48

What percentage of bile salts are lost each day?

Back 48

5%

Front 49

Besides statins, what is a method of reducing the amount of cholesterol in the body?

Back 49

since most cholesterol in bile salts is recycle, increasing the amount secreted would lower the total cholesterol

Front 50

Where does much of the cholesterol used in steroid hormones (cortisol) come from?

Back 50

the liver

Front 51

Why, in the transport of cholesterol, are they packaged as cholesterol esters?

Back 51

they are more hydrophobic and thus package better in to lipoproteins

Front 52

Which enzyme removes the ester from the cholesterol?

Back 52

Lipase

Front 53

What is the overall pathway in vitamine D synthesis?

Back 53

1) 7-dehydrocholesterol --> UV light on skin --> goes to liver --> converted to 25-hydroxycholecalciferol --> goes to kidney --> converted to 1,25-dihydroxycholecalciferol by 1-∂-hydroxylase.

Front 54

What positively regulates 1-∂-hydroxylase in vitamin D synthesis in the kidneys?

Back 54

PTH

Front 55

What would a person who is malnurished, has reduced sunlight and renal failure have? What else would cause this?

Back 55

a) vitamin D deficiency… b) malobsorption of fat (vitamin D is fat soluble, thus a bile salt synthesis can cause a vitamin D deficiency)

Front 56

A person with statorrhea "floaties" may also have what deficiency? Why?

Back 56

a)Vitamin D… b) fat malabsorption due to bile synthesis or secretion

Front 57

Where does much of the cholesterol used in steroid hormones (cortisol) come from?

Back 57

the liver

Front 58

Done... exit this set of flash cards... the rest are repeats

Back 58

Done

Front 59

Which enzyme removes the ester from the cholesterol?

Back 59

Lipase

Front 60

What is the overall pathway in vitamine D synthesis?

Back 60

1) 7-dehydrocholesterol --> UV light on skin --> goes to liver --> converted to 25-hydroxycholecalciferol --> goes to kidney --> converted to 1,25-dihydroxycholecalciferol by 1-∂-hydroxylase.

Front 61

What positively regulates 1-∂-hydroxylase in vitamin D synthesis in the kidneys?

Back 61

PTH

Front 62

What would a person who is malnurished, has reduced sunlight and renal failure have? What else would cause this?

Back 62

a) vitamin D deficiency… b) malobsorption of fat (vitamin D is fat soluble, thus a bile salt synthesis can cause a vitamin D deficiency)

Front 63

A person with statorrhea "floaties" may also have what deficiency? Why?

Back 63

a)Vitamin D… b) fat malabsorption due to bile synthesis or secretion