Mnpc Iii Exam 1- Cholesterol

Front 1

FUNCTIONS OF CHOLESTEROL IN THE BODY (4)

Back 1

structural component in membranes of cells
precursor to bile acids
precursor to all steroids
precursor to vit D3

Front 2

Cholesterol to vitamin D3 steps (3)

Back 2

1) NADP -->add double bond on C7 (7-dehydrocholesterol)
2) light--> double bonds rearrange and open up
3) isomerization -->vitamin D3

Front 3

cholesterol location in body

Back 3

ubiquitous

Front 4

organ Especially rich in cholesterol

Back 4

brain

Front 5

grams of cholesterol in body

Back 5

500 g

Front 6

% of cholesterol in plasma

Back 6

1%

Front 7

cholesterol input into body- dietary and synthesis amount

Back 7

Dietary intake- 300 mg/day
synthesis- 1g/day

Front 8

2 main tissues that make cholesterol

Back 8

all tissues make, but main is
liver and GI

Front 9

Cholesterol synthesis occurs in what part of the cell (2)

Back 9

microsomal part
endoplasmic reticulum

Front 10

Building Block of cholesterol

Back 10

acetyl CoA

Front 11

how to calc Number of Possible isomers

Back 11

2^n where n = # of asymmetric carbons

Front 12

lanosterol- how many carbons
made from what?

Back 12

30
made from 18 acetates

Front 13

cholesterol synthesis- 3 main steps

DRAW STUPID PATHWAYS

Back 13

MEVALONIC ACID FORMATION
SQUALENE FORMATION
CYCLIZATION AND PROCESSING

Front 14

Elimination of cholesterol from the body- what happens in the rxn and where

Back 14

reduction of the double bond in liver/intestine

Front 15

METABOLIC REACTIONS OF CHOLESTEROL (5 total)

Back 15

epimerization- 3b-OH --> 3a-OH
reduction- of double bond @ carbon 5 to 5b-H (rings A/B fusion is cis)
hydroxylation via P450 hydroxylase at 7a and 12a position
oxidation of alcohols to ketone (C3, 7, 12)
Oxidation of the 17-alkyl group to give a 24 carboxylic acid (i think he just means the group itself gets oxidized so that C24 is now a carboxylic acid)

Front 16

4 major bile acids (know structure)

Back 16

cholic acid
7-deoxycholic acid
chenodeoxycolic acid (chenodiol) what the fuck they only added cheno because it means goose and they got it from a goose ahglwehgkwag
decholin

Front 17

bile acid conjugates with amino acids (2)

Back 17

cholic acid +glycine = glycholic acid
cholic acid + taurene = taurocholic acid

Front 18

CHOLESTEROL PRODUCTS on the market (like...made...from bile acids) (3)

Back 18

bile salts (biron)- used as digestant
chenodiol (chenix)- aids in dissolution of gallstones
monooctanoin- glyceride digestant

Front 19

types of lipidemias (4)

Back 19

hyper
hypo
primary- genetic deficiencies or mutations
secondary- result of other conditions (alcoholism, diabetes...)
must treat underlying disease

Front 20

causes of secondary hyperlipidemia (3)

Back 20

alcoholism, diabetes, thyroid (hypo)

Front 21

3 Hypercholesterolemias and their physiological defects

Back 21

familial hypercholesterolemia (deficiency of LDL-R = increase LDL)
familiar defective apoB-100 (increase LDL)
polygenic hypercholesterolemia (increase LDL)

Front 22

3 Hypertriglyceridemias and their physiological effects

Back 22

familial hypertriglyceridemia- increase VLDL
familial lipoprotein lipase deficiency- increase chylo
familial apoC-II deficiency- increase chylo; ApoC needed to bind lipoprotein lipase

Front 23

2 types of Mixed
Hypercholesterolemia
and Hypertriglyceridemia diseases

Back 23

Familial combined
hyperlipidemia- increased VLDL/LDL
dysbetalipoproteinemia- increased VLDL/IDL (presence of apoE2 isoforms?)

Front 24

4 of the primary hyperlipidemia diseases that put pt at high risk for atherosclerosis

Back 24

familiar hyperhcolesteremia
familiar defective apoB-100
poygenic hypercholesterolemia
(all the increased LDL ones)
familial combined hyperlipidemia

Front 25

2 primary hyperlipidemia diseases that do not elevate atherosclerosis risk

Back 25

familial lipoprotein lipase deficiency
familial apoC-II deficiency

(both boost chylomicrons)

Front 26

2 primary hyperlipidemias that put pt at moderate risk for athersclerosis

Back 26

Familial
hypertriglyceridimia

Dysbetalipoproteinemia

(increase VLDL/IDL- not LDL)

Front 27

CHD risk: total cholesterol level ranges (3)

Back 27

total cholesterol > 240 = high
200-239 = moderate
<200 = low

Front 28

CHD risk LDL level ranges (3)

Back 28

<130
130-159
>160

Front 29

CHD risk: HDL level ranges (2)

Back 29

>35 = moderate
<35 = high

Front 30

Triglyceride level that gives high CHD risk

Back 30

>250

Front 31

bile acid sequestrants- elimination, absorption NOT from where, what does it do

Back 31

eliminated in the feces
effective in decreasing plasma cholesterol and LDL levels
not orally absorbed

Front 32

bile acid sequestrants classified as what type of...thing/drug

Back 32

classified as anion exchange resins (+ charge so bind to - charged bile acids)

Front 33

bile acid sequestrants- physically they do what? (bind to...) (2)

how does this cause a reduction in plasma cholesterol?

Back 33

binds to glycholic acid and taurocholic acid


decreased concentrations of bile acids are returned to the liver which increases hepatic conversion of cholesterol to bile acid

essentially removes the feedback inhibition of 7a-hydroxylase enzyme (the enzyme that makes cholic acid from cholesterol)

Front 34

general structure of bile acid sequestrants- how does they have positive charge

Back 34

quaternary ammoniums on co-polymers

Front 35

cholestyramine- water solubility, made up of what 2 compounds

Back 35

not water soluble
co-polymer of polysterene and divinylbenzene

Front 36

2 types of stpuid bile sequestrants

Back 36

cholestipol
cholestyramine

Front 37

colestipol- made up of what 2 compounds

Back 37

co-polymer of tetraethylene pentamine and epichlorhydride

Front 38

Statins MoA (2 step process) state competitive or suicide

Back 38

HMG CoA Reductase competitive inhibitor (the rate
limiting enzyme in cholesterol synthesis-- reduces the production of mevalonic acid from HMG-CoA)

this then
results in a compensatory increase in the expression of
LDL receptors on hepatocyte membranes and a stimulation
of LDL catabolism.

Front 39

how many statins approved for use in US

Back 39

7

Front 40

HMG CoA stands for...

Back 40

3-hydroxy-3-methyl-glutamyl coenzyme A

Front 41

pharmacophore of statin

Back 41

---

Front 42

first statin discovered
isolated from..
affinity compared to endogenous substrate

Back 42

mevastatin
isolated from penicillum citrinisusudf
affinity 10k greater than endogenous substrate

Front 43

lovastatin (first statin approved by FDA)
SAR- 2 parts of note

Back 43

methyl group makes this 2x more potent than mevastatin
lactone needs to be metabolized to carboxylic acid (prodrug)

Front 44

lovastatin isolated from...

Back 44

aspergillus terreus (NP)

Front 45

simvastatin- derived from what? (what kind synthesis is this called)
SAR- 2

Back 45

derived synthetically from lovastatin (semi synthetic)
also prodrug
extra methyl group- 1 less stereocenter (added just to make it different from lovastatin...)

Front 46

pravastatin isolated from...

Back 46

isolated from nocardis autotrophis

Front 47

pravastatin- what is unique about its structure

Back 47

open ring- not a prodrug

Front 48

fluvastatin- how is it produced
"extra" activity
structural differences to simvastatin

Back 48

synthetic drug
anti-viral activity against hepatitis C
doesn't have decalin found in others (know it is synthetic)
has fluoride- to iD structure

Front 49

atorvastatin- synthesis and structural differences to simvastatin

Back 49

synthetic- no decalin (can tell it's not NP because it has no decalin)
also has fluoride...but its bigger than fluvastatin

Front 50

random screening of what compound discovered utility of fibrates?

Back 50

random screening test of aryloxy isobutyric acid demonstrated that these compounds (fibrates) could lower both plasma cholesterol and total lipid levels

Front 51

fibrates- what do they do in the body (2 things)

Back 51

decrease both plasma TG and cholesterol- but more so TG

Front 52

clofibrate- SAR
lowers cholesterol by how much?

Back 52

prodrug (ester)- active form is carboxylic acid
lowers cholesterol 9%

Front 53

fenofibrate- SAR
does what 3 things (all fibrates i think do this)

Back 53

prodrug

1. Increase the activity of lipoprotein lipase
2. Clears chylomicrons and VLDL quickly
3. Lowers triglycerides (VLDL) and raises HDL cholesterol

Front 54

gemfibrozil- came from where (derived from what)

Back 54

clofibrate SAR

Front 55

MoA of probucol (3 ways it works)

Back 55

Increases the fecal loss of bile acid-bound low
density lipoprotein cholesterol, decreases the synthesis of cholesterol and
inhibits enteral cholesterol absorption

Front 56

Dextrothyroxine Sodium- structure- what is it derived from

Back 56

R-isomer of thyroid hormone (which is S)
don't know MoA but somehow lowers cholesterol

Front 57

Niacin (nicotinic acid)- a.k.a?
synthed by what rxn from what compound
MoA (2)

Back 57

vitamin B3
synthesized by oxidation of nicotine
increases levels of HDL
decreases VLDL (Inhibits VLDL secretion therefore ultimately decreases production of LDL)

(does all this by inhibiting breakdown of adipose)

Front 58

daily amt of Vit B3 needed
dose of niacin as antilipemic agent

Back 58

daily amount needed as vitamin B3 is 14-16 mg/day

dose as antilipemic agent is 0.5-1.5g

Front 59

Ezetimibe (zetia)- what family?

Back 59

2-azetidone family

Front 60

what is an azetidone

Back 60

4 membered ring w/e a nitrogen and a carbonyl

Front 61

ezetimibe MoA

better to use with what?

Back 61

better to use with a statin

Inhibits absorption
of cholesterol at the brush border of the
small intestine

Front 62

ezetimibe MoA leads to what 3 results (physiologically what happens to cholesterol)

Back 62

decreased
delivery of cholesterol to the liver,
reduction of hepatic cholesterol stores and
an increased clearance of cholesterol from
the blood

Front 63

ezetimibe decreases what 4 things and increases what 1 thing

Back 63

decreases total cholesterol, LDLcholesterol,
ApoB, and triglycerides while
increasing HDL-cholesterol.

Front 64

vytorin

Back 64

ezetimibe + simvastatin