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Flashcards in Biochem Week 2 Deck (56):
1

Cholesterol is an important precursor to what three compounds?

1) bile salts/acids
2) hormones
3) precursor to vitamin D

2

Name the 5 sex chromosomes that cholesterol is a precursor to

progesterone, estrogens, testosterone, cortisol, aldosterone

3

True/False: Humans have about 1000 grams of cholesterol, mostly in membranes

FALSE 100 grams
it is mostly in membranes doe

4

True/False: Gallstones can be over 80% cholesterol

TRUE DAT

5

______ allow for effective treatment for high cholesterol and were developed in the 1990s

statins

6

True/False: Cholesterol makes membranes more fluid

False, makes them more rigid

7

True/False: The hydroxyl group on cholesterol interacts with surfaces of membrane

true

8

Myelin membranes are especially ___ in cholesterol

high

9

Describe the polarity of cholesterol

Cholesterol is very apolar [hydrophobic]
it interacts well with apolar alkyl groups in membranes

10

How many rings does cholesterol have?
What functional groups does it have and at what positions?
Does it contain any double bonds or side chains?
How many carbons in total?

4 rings
hydroxyl at position 3
methyl groups at 18 and 19
double bond between c5 and c6
8 carbon side chain
27 total carbons
PLANAR MOLECULE

11

Concentration of cholesterol in the blood is about twice that of ____ but both are about ____ mM

glucose, 5

12

Most of the cholesterol in the blood is in what form? How is it carried?

cholesterol ester
very nonpolar
carried in the form of lipoproteins

13

What two compounds can be added to produce cholesterol esters from cholesterol?
What enzymes are involved?

fatty acyl-CoA
or
lecithin

acyl-CoA cholesterol acyl transferase (ACAT)

lecithin cholesterol acyl transferase (LCAT)

14

Describe the major details of cholesterol biosynthesis

acetyl-coa is converted to mevalonate which is converted to isoprene

from there, 6 5carbon intermediates are used to form a 30 carbon molecule called squalene which is converted to 27 carbon molecule cholesterol through 5 add'l steps

15

Humans synthesize about 1/2 of cholesterol we have from ______ which can come from ______ or ______ and must get to ______

acetyl-CoA, carbohydrates, fatty acids, cytoplasm

16

What is needed in the cytoplasm to make cholesterol (2 compounds)

acetyl coa
nadph

17

What are the two sources of acetyl coa?

glycolysis
beta oxidation of fatty acids

18

How is acetyl coa transported into the cytoplasm from the mitochondrial matrix?

it is used in the citrate synthesis reaction [oxaloacetate + acetyl Coa --> citrate]
citrate is then transported to the cytoplasm where the reverse reaction occurs and an acetyl coa is produced

19

The __________ is a major source of NADPH [shunt]

pentose phosphate pathway

20

In the cytoplasm, citrate is converted to oxaloacetate, producing ______ which is then converted to malate. Malate is converted to pyruvate by _______ [important enzyme]

acetyl coa; malic enzyme

21

2 AcetylCoA in cytoplasm join to form _________ which join with another acetylCoA to make ________ in a reaction catalyzed by _________

acetoacetylCoA, HMG CoA, HMG CoA synthase

22

What is the destiny of Hmg CoA made in cytosol? in mitochondrial matrix?

in cytosol, goes to cholesterol

in mito matrix, goes to ketone bodies

23

What is the key regulated step in cholesterol biosynthesis? [and in almost every regulatory mechanism known in biochemistry]

HMG CoA + 2NADPH + 2H+ --> mevalonate + CoA + 2NADP+

CATALYZED BY HMG COA REDUCTASE

24

There are several ways that HMG-COA reductase is inhibited. _______ of the enzyme, for example, decreases its activity

phosphorylation

25

There are several ways that HMG-COA reductase is inhibited. The rate of translation of the enzyme is inhibited by __________ and _________

non-sterol metabolites, dietary cholesterol

26

There are several ways that HMG-COA reductase is inhibited. An increase in ______ increases the rate of HMG-CoA reductase degradation

cholesterol

27

There are several ways that HMG-COA reductase is inhibited. Describe the relationship between sterol regulatory element binding proteins (SREBPs) and this inhibition.

SREBPs are transcription factors that bind to the sterol regulatory element DNA sequence.
When there are low levels of sterols, the SREBPs are cleaved and translocated to the nucleus where they bind to specific sterol regulatory element DNA sequences thus upregulating enzymes involved in sterol synthesis
However, sterols inhibit the cleavage of SREBPs and thus reduce synthesis of add'l sterols.

28

Sterol regulatory element binding proteins (SREBPs) belong the to the basic ______________ class of transcription factors

helix-loop-helix leucine zipper

29

Where are unactivated SREBPs found? Describe their movement under low sterol levels.

When inactive, attached to the ER and nuclear envelope.
Low sterol levels prompt movement to Golgi apparatus where they are cleaved by proteases. The protein then enters the nucleus where it increases transcription of target genes that inc synthesis of HMG-CoA reductase.

30

Describe why diet and exercise may not be effective in lowering cholesterol levels.

There is a direct feedback inhibition by cholesterol or cholesterol product on HMG-CoA reductase.

Therefore, the higher the cholesterol in your diet, the less you make.
AND the less cholesterol in your diet, the more you make.

31

Describe how statins work in reducing cholesterol levels

They are competitive inhibitors of HMG-CoA Reductase.

Two examples are Atorvastatin (Lipitor) and Lovastatin (Mevacor).

The top parts of the molecules look very similar.

32

What is a side effect of using statins?

Inhibiting HMG CoA reductase decreases ubiquinone (CoQ) production. 2-10% of people will have muscle pain. Little evidence that CoQ supplementation helps.

33

What is CoQ (ubiquinone)'s function in the cell?

It is a key intermediate in the electron transport chain

34

Describe the basics of how mevalonate is converted to squalene

Mevalonate goes to a C5 then a C10 and then a C15. Two C15s condense to a C30 which then goes to cholesterol (C27)

35

Squalene then goes through a series of steps to produce cholesterol with a single OH group. There are about 19 _______ steps in this sequence

cytochrome p450

36

True/False: We make about 1/2 of cholesterol in our bodies

true

37

Overall, acetyl CoA is converted to C5 ______ then three C5 intermediates condense to form C15 _____. Then two C15 intemermediates form the _______ squalene.

hemiterpenoids; sequiterpenoid; triterpenoid

38

Squalene is cyclized to a ____ membered ring structure. The C30 intermediate is modified to cholesterol in a series of over 30 enzymatic reactions. ______ play major role in modifying the C30 intermediate.

four, cytochrome p450

39

True/False: Much of cholesterol is made in liver

true

40

The major metabolic fate of cholesterol is conversion to ______ which occurs in the ______

bile acids, liver

41

Bile salts are stored in the ______ then transported to ______ and function to ________

gallbladder, small intestine, solubilize lipids

42

True/False: most of bile salts are reabsorbed and recycled

true

43

True/False: Cholesterol is present in bile acids in large amounts

false, small amounts

44

What happens when gallbladder is removed in terms of bile acids?

Bile acids go directly into the small intestine

45

95% of biliary secretion undergoes portal venous return to _____. Overall, biliary secretion is recycled about _____

hepatocytes; 4-12 cycles per day

46

True/False: Liver synthesizes about 0.2 to 0.6 gms of cholesterol per day, and roughly twice that amount is excreted

false, equal amount excreted

47

What is the key difference between a bile salt and cholesterol?

Bile salts are polar forms of cholesterol
They have shorter side chain! C5 instead of C8!

48

What are the four common bile acids? What is the most common?

1) cholic acid
2) deoxycholic acid
3) chenodeoxycholic acid (41%)
4) lithocholic acid

49

Bile acids have ______ groups. In addition, they may have more ____ groups than cholesterol.

carboxyl (COOH), OH

50

What two compounds are added to bile acids to make them more soluble?

glycine [produces glycocholic acid]
taurine [produces taurocholic acid]

these conjugates have pKa of 1-4
non-conjugates have pka of 7.0

pH of duodenum is 3-5

51

Bile salts are planar _____

amphipaths

52

Describe the role of bile salts

Bile salts are emulsifying agents that facilitate dietary fat digestion in the small intestine. They are synthesized in the liver from cholesterol.

53

The bile acid cholic acid or ____ is produced from cholesterol in a series of reactions. Two of these reactions are ______ catalyzed by _____ enzymes.

cholate, cytochrome p450 enzymes

54

From cholic acid, the bile salt _______ is produced when cholyl-CoA reacts with glycine to form an ______ bond linkage

glycocholate, amide

55

What is cholestyramine?

What are its side effects?

It is a compound that is not absorbed and attracts bile salts which bind to its positive charge. This removes bile salts from the body and thus less are recycled. The liver has to use more cholesterol to make more bile salts, and thus lowers cholesterol.

Side fx are diarrhea and discomfort.

56

True/False 90-95% of bile salts are reabsorbed and reused via enterohepatic circulation

true