Cholesterol Biosynthesis and Transport Genetics Part 1

Question 1

cholesterol is a precursor for (3)

Answer 1

vitamin D
steroids
bile salts

Question 2

cholesterol is necessary for — —

Answer 2

membrane stability

Question 3

cholesterol is a major structural component of — —

Answer 3

myelin sheaths

Question 4

myelin sheaths are synthesized by glial (what types of glial cells) cells and which surround axons in vertebrates

Answer 4

PNS: schwann cells
CNS: oligodendrocytes

Question 5

what are nodes of ranvier?

Answer 5

non myelinated regions with a high concentration of Na+ channels which initiate depolarization of the membrane

Question 6

all steroids contain the same four — —

Answer 6

hydrocarbon rings

Question 7

the major portion of the molecule is — but the hydroxyl group is —

Answer 7

hydrophobic, hydrophilic

Question 8

what two ways can cholesterol be absorbed?

Answer 8

dietary sources

synthesized de novo

Question 9

what are the two main organs which synthesize cholesterol?

Answer 9

liver (70-80%)
small intestine (10%)

Question 10

cholesterol is also produced in the (2)

Answer 10

adrenal glands and gonads

Question 11

why is cholesterol a critical component of cell membranes (~30%)?

Answer 11

it regulates membrane fluidity and has important functions in intracellular transport, cell signaling, and nerve conduction

Question 12

cholesterol is the precursor for the biosynthesis of (3)

Answer 12

steroid hormones, bile acids, and vitamin D

Question 13

an adults on a low cholesterol diet typically synthesizes about — mg of cholesterol on a daily basis

Answer 13

800 (de novo, liver)

Question 14

LDL
most desirable
very high

Answer 14

under 100

over 190

Question 15

HDL
undesirable
good, risk lowered

Answer 15

under 40

over 60

Question 16

stage 1 of de novo biosynthesis of cholesterol

Answer 16

the synthesis of isopentenyl pyrophosphate

this stage becgins with the condensation of acetyl-coA and acetoacetyl-coA in the cytoplasm to form 3-hydroxyl-3-methylglutaryl coA (HMG-coA), which is then reduced to mevalonate by the enzyme HGM-coA reductase. mevalonate is then converted into isopentyl pyrophosphate

Question 17

stage 2 of de novo biosynthesis of cholesterol

Answer 17

the condensation of 6 molecules of isopentyl pyrophosphate to form squalene

Question 18

stage 3 of de novo biosynthesis of cholesterol

Answer 18

the cyclization of squalene to form the steroid 4-ring structure, which rearranges to form lanosterol. lanosterol is then converted into cholesterol

Question 19

first committed step of cholesterol biosynthesis

Answer 19

HMG-coA is reduced by HMG-coA reductase to form mevalonate

Question 20

in the cytosol, HGM-coA is converted into mevalonate whereas in the mitochondria, it is converted to — and —, which are further processed into — —

Answer 20

acetyl coA and acetoacetate

ketone bodies

Question 21

what produces all of the acetyl coA?

Answer 21

fatty acid beta-oxidation

Question 22

the source of carbon atoms in cholesterol are synthesized from

Answer 22

acetate

Question 23

the rate of synthesis of reductase mRNA is controlled by the

Answer 23

sterol regulatory binding proteins (SREBP)

Question 24

SREBP is a

Answer 24

transcription factor

Question 25

this process is regulated by levels of cholesterol available by the --- and --- proteins that bind cholesterol

Answer 25

INGIG | SCAP

Question 26

INSIG and SCAP act as --- to tell us if we need to keep SREBP available

Answer 26

sensors

Question 27

the rate of translation of reductase mRNA is inhibited by metabolites derived from --- as well as --- ---

Answer 27

mevalonate | dietary cholesterol

Question 28

degradation of the reductase is tightly controlled by ---

Answer 28

lanosterol

Question 29

phosphorylation of the enzyme decreases the activity of the

Answer 29

reductase

Question 30

this enzyme, along with acetyl-coA carboxylase which catalyzes a similar committed step in fatty acid biosynthesis, is switched off by an --- --- --- ---

Answer 30

AMP-activated protein kinase

Question 31

fatty acid and cholesterol biosynthesis cease when --- is low in the cell

Answer 31

ATP

Question 32

why does FA and cholesterol biosynthesis cease when ATP is low in the cell?

Answer 32

cholesterol and FA are not needed when ATP is low. these are ATP requiring steps, so they wont occur when ATP is low

Question 33

synthesis of cholesterol and fatty acids is regulated by transcription factors --- and ---

Answer 33

SREBP 1 and SREBP 2

Question 34

SREBP target genes are used in (4)

Answer 34

cholesterol metabolism fatty acid metabolism triglyceride synthesis plasma lipoprotein metabolism

Question 35

SREBP target genes in cholesterol metabolism (7)

Answer 35

``` LDL receptor HGM coA synthase HGM coA reductase farnesyl diphosphate synthase squalene synthase SREBP-2 lanosterol-14-alpha-demethylase (cyp51) ```

Question 36

SREBP target genes in fatty acid metabolism (8)

Answer 36

``` acetyl coA carboxylase fatty acid synthase stearoyl coA desaturase-1 and 2 acyl-coA binding protein (diazepam) SREBP-1 ATP citrate lyase PPAR gamma acetyl coA synthetase ```

Question 37

SREBP target genes in triglyceride synthesis (1)

Answer 37

glycerol-3-phosphate acyltranferase

Question 38

SREBP target genes in plasma lipoprotein metabolism (2)

Answer 38

``` lipoprotein lipase HDL receptor (SRBI) ```

Question 39

statins act by competitively inhibiting

Answer 39

HMG-coA reductase

Question 40

by inhibiting HMG-coA reductase, the amount of --- produced is reduced

Answer 40

mevalonate

Question 41

reduced mevalonate ultimately leads to reduced --- synthesis

Answer 41

cholesterol

Question 42

when the liver can no longer produce cholesterol, levels in the blood will fall since most of the circulating cholesterol comes from

Answer 42

internal synthesis, rather than diet

Question 43

cholesterol synthesis occurs mostly at --- so statins with a short like are usually taken at --- to maximize their benefit

Answer 43

night

Question 44

statins inhibit the reabsorption of

Answer 44

ostetoclasts

Question 45

statins inhibit the reabsorption of osteoclasts since they also inhibit the formation of prenylated proteins which is required for

Answer 45

osteoglastogenesis

Question 46

what do statins ressemble?

Answer 46

the 3-hydroxy-3-methylglutaryl moiety recognized by HMG-coA reductase

Question 47

statins act as a competitive inhibitor by preventing

Answer 47

HMG-coA reductase from producing HMG-coA

Question 48

bisphosphonates are used for treating bone diseases such as --- and ---

Answer 48

osteoporosis | osteogenesis imperfecta

Question 49

bisphosphonates inhibit

Answer 49

osteoclast resorption of bone

Question 50

pyrophosphate is an inhibitor of

Answer 50

mineralization

Question 51

what was the first bisphosphonate developed?

Answer 51

alendronate

Question 52

zoledronate is a bisphosphonate used to treat

Answer 52

osteocronosis of the jaw

Question 53

what is protein prenylation?

Answer 53

post-translational modification of proteins that adds a farnesyl or geranylgeranyl to the c-terminal cysteines of target proteins

Question 54

the prenylation adds a --- --- to the target protein, which can serve to

Answer 54

hydrophobic molecule | anchor the protein to the membrane surface

Question 55

what is the role of prenylation in osteoclast function?

Answer 55

prevents osteoclasts from resorption of bone

Question 56

prenylation in osteoclast function

Answer 56

small GTPase localize to specific membrane compartments and assist in cytoskeleton rearrangement needs to form the sealing zone. this localization is dependent upon post-translational prenylation of these GTPases

Question 57

bile salts are made in the --- and stored in the --- between meals

Answer 57

liver | gallbladder

Question 58

after we eat and there are fats present in our digestive tracts, out hormones send. signal to our gallbladders to

Answer 58

release bile

Question 59

bile salts aid in digestion by breaking down

Answer 59

fats

Question 60

bile salts help absorb

Answer 60

fat-soluble vitamins

Question 61

bile salts eliminate

Answer 61

waste products