Cholesterol and Bile Acid Metabolism

Question 1

The major components of bile include

Answer 1

Bile acids, phospholipids, and cholesterol

Question 2

Contains bilirubin, electrolytes such as Na+, K+, and HCO3-, and small amounts of proteins

-Also copper

Answer 2

Bile

Question 3

Bile has two fundamental functions. What are they?

Answer 3

1. ) Lipid digestion and absorption

2. ) Excretion of cholesterol and bilirubin

Question 4

Fatty acids in the duodenum stimulate the release of

Answer 4

CCK

Question 5

Leads to the contraction of the gall bladder and the relaxation of the sphincter of Oddi to release bile into the duodenum

Answer 5

CCK

Question 6

Are amphipathic, i.e. they have both hydrophobic and hydrophilic properties

Answer 6

Bile Salts

Question 7

The hydrophilic parts of bile are the two or three

Answer 7

OH groups and a negative charge

Question 8

While superficially similar to cholesterol, the additional hydroxyl groups are all

Answer 8

Below the plane of the ring

-methyl groups are above

Question 9

Hence the amphipathic nature to these compounds, which plays into their role as

Answer 9

Detergents in the digestion process

Question 10

Bile acids facilitate lipid digestion through emulsification of fat and formation of

Answer 10

Micelles

Question 11

Transport the digested products of triacylglycerides (monoglycerides and free fatty acids), which are rather insoluble to the brush borders of epithelium for absorption

Answer 11

Bile salt micelles

Question 12

Plays an essential role in liver homeostasis

Answer 12

Liver

Question 13

A 27-carbon hydrophobic four-ringed compound that is an essential component of cell and organelle membranes

Answer 13

Cholesterol

Question 14

Cholesterol is particularly abundant in the CNS in

Answer 14

Myelinated sheaths

Question 15

Because of its insolubility in water, cholesterol is transported in the plasma as a component of

Answer 15

Lipoproteins

Question 16

Cholesterol is not transported as free cholesterol but rather as an

Answer 16

Esterified version (i.e. w/ a fatty acid attached)

Question 17

Cholesterol is the precursor of other important products as well, including the steroid hormones and the

Answer 17

Bile acids

Question 18

The cardiac pathologies associated with cholesterol stem from the regulation of its abundance in the serum, packaged in

Answer 18

Lipoproteins

Question 19

A hydrophobic compound and therefore does not exist dissolved in the aqueous environment of blood as a free compound

Answer 19

Cholesterol

Question 20

The body’s supply of cholesterol, derived from the diet and from de novo synthesis, is always transported in the blood packaged into

Answer 20

Lipoproteins

Question 21

Most of the cholesterol in a lipoprotein is located where?

Answer 21

Buried in interior in esterified form

Question 22

Apart from its roles in cell and organelle membranes, cholesterol is the starting substrate in which three principal biosynthetic pathways?

Answer 22

1. ) Steroid hormones
2. ) Vitamin D
3. ) Bile salts

Question 23

Bile salts help to excrete the end product of heme degredation which is called

-gives feces a dark color

Answer 23

Bilirubin

Question 24

In humans, the ring structure of cholesterol can not be metabolized to

Answer 24

CO2 and H2O

Question 25

Synthesis and subsequent excretion of bile acids in the feces represent the only significant mechanism for the elimination of excess

Answer 25

Cholesterol

Question 26

Once transported to the intestine for elimination, some of the cholesterol is modified to coprostanol and cholestenol by

Answer 26

Gut Bacteria

Question 27

Together with cholesterol, make up the bulk of neutral fecal sterols

Answer 27

Coprostanol and cholestenol

Question 28

The only mechanism the body possesses to eliminate cholesterol is via the bile acids in the feces and by secretion of cholesterol into the bile, which transports it to the intestine for

Answer 28

Elimination

Question 29

The liver synthesizes which two primary bile acids from cholesterol?

Answer 29

1. ) Cholic acid | 2. ) Chenodeoxycholic acid

Question 30

When these primary bile acids are secreted into the lumen of the intestine, a portion of each is dehydroxylated by gut bacteria at

Answer 30

C-7

Question 31

This dehydroxylation creates the two secondary bile acids called

Answer 31

Deoxycholic acid and lithocholic acid

Question 32

Thus how many bile acids are there?

Answer 32

Four

Question 33

What is more soluble, primary bile acids or secondary bile acids?

Answer 33

Primary

Question 34

The initial products of bile-targeted cholesterol metabolism in the liver

Answer 34

The primary bile salts cholic acid and chenodeoxycholic acid

Question 35

Their synthesis from cholesterol is a multi step process; the rate limiting step being catalyzed by

Answer 35

7a-hydroxylase (CYP7A)

Question 36

Hydroxylates cholesterol at the 7 position to form the primary bile acids

Answer 36

CYP7A

Question 37

This enzyme is found only in the liver and it is localized to the ER

Answer 37

CYP7A

Question 38

When bile acids accumulate, synthesis is reduced by a negative feedback mechanism that decreases the expression of

Answer 38

CYP7A

Question 39

Induces bile acid synthesis by activating cholesterol 7a-hydroxylase in some but not all species

Answer 39

Cholesterol accumulation

Question 40

The most abundant bile acids in the human bile are

Answer 40

Chenodeoxycholic acid and cholic acid

Question 41

The pKa of bile acids is approximately

Answer 41

6

Question 42

Therefore, in the contents of the intestinal lumen, which normally have a pH of 6, approximately 50% of the molecules are present in the protonated form and 50% are ionized, which form

Answer 42

Bile Salts

Question 43

The ionized form of bile acids

Answer 43

Bile salts

Question 44

Before the primary bile acids are secreted into the canalicular lumen they are conjugated via amide linkages of

Answer 44

Glycine or taurine to the rings carboxyl group

Question 45

This amide linkage produces the primary bile salts

Answer 45

Glycocholic acid and taurocholic acid

Question 46

Have pKa values that are much lower than the pH of the intestinal lumen, therefore a higher percentage of the molecules is present in the ionized form

Answer 46

Glycocholic acid and taurocholic acid

Question 47

These modifications help to further enhance their hydrophilicity as well as decrease their

Answer 47

Cytotoxicity

Question 48

The conjugated bile acids are the major solutes in

Answer 48

Human Bile

Question 49

During the enterohepatic recycling of bile acids, the structure is altered by bacterial enzymes in the

Answer 49

Distal intestine

Question 50

First, intestinal bacteria deconjugate the bile salts, removing the

Answer 50

Glycine and Taurine

Question 51

The 7-hydroxyl group of C7 is also attacked by

Answer 51

Anaerobic bacteria in the colon

Question 52

The secondary bile acids may be reconjugated in the liver, but they are not

Answer 52

Rehydroxylated

Question 53

Therefore, more than 95% of the biliary bile acids in healthy humans are

Answer 53

Cholic acid, chenodeoxycholic acid, and deoxycholic acid

Question 54

Virtually all of the biliary bile acids are in the

Answer 54

Conjugated form

Question 55

On the other hand, fecal bile acids are almost entirely

Answer 55

Unconjugated

Question 56

Fecal bile acids consist primarily of the dehydroxylated bile acids

Answer 56

Deoxycholic acid and lithocholic acid

Question 57

Implies the movement of bile acids from the liver to the small intestine and back to the liver

Answer 57

Enterohepatic circulation

Question 58

The bile acid pool contains about

Answer 58

2-4g of bile acid

Question 59

This pool is recycled via the enterohepatic circulation on the order of six to ten times each day, so that how much bile enters the duodenum during a 24 hr. period?

Answer 59

15-30g

Question 60

Of the total bile salt pool, how much is excreted in feces per day?

Answer 60

0.2-0.6 g per day

Question 61

Bile acids traverse the hepatocyte and are actively secreted into canalicular bile, completing the

Answer 61

Enterohepatic Cycle

Question 62

Ileal bile salt transport is highly efficient (about 95%), but approximately 0.2-0.6 g of bile salts escapes the

Answer 62

Enterohepatic cycle each day

Question 63

This loss of bile acids in the feces represents the body’s sole mechanism for elimination of the four-membered ring originally derived from

Answer 63

Cholesterol

Question 64

In the liver, bile acids are efficiently transported from portal blood by the

Answer 64

Na+-taurocholate cotransporting polypeptide (NTCP)

Question 65

These bile salts are then resecreted across the canalicular membrane by the

Answer 65

Bile salt export pump (BSEP)

Question 66

In the terminal ileum, bile salts are efficiently absorbed in by the

Answer 66

Apical Sodium Bile acid Transporter (ASBT)

Question 67

In the terminal ileum, they are efficiently absorbed in by the apical sodium bile acid transporter (ASBT) and transported out by the basolateral -returns bile salts to liver in portal circulation

Answer 67

Heteromeric transporter, OSTα-OSTβ

Question 68

A small percentage of the bile salts are not reabsorbed and are modified from primary bile acids to secondary bile acids by anaerobic bacteria present in the

Answer 68

Colon

Question 69

These secondary bile acids are either passively absorbed from the colon or they are

Answer 69

Excreted in feces

Question 70

Represents one of the most common surgical problems worldwide and is especially prevalent in most western countries

Answer 70

Cholelithiasis (or gallstones)

Question 71

In the U.S. alone, gallstones are present in 8-20% of the population by the age of 40 and are more likely to develop in women than in men by a ratio of about

Answer 71

2-3:1

Question 72

What are the three varieties of gallstones?

Answer 72

1. ) Cholesterol stones (75%) 2. ) Pigmented stones (15-20%) 3. ) Mixed

Question 73

The most common type of gall stone is the

Answer 73

Cholesterol stone

Question 74

Arise from the crystallization of calcium bilirubinate

Answer 74

Pigmented stones

Question 75

Increased red blood cell destruction (hemolysis) and abnormal metabolism of hemoglobin (liver disease) cause

Answer 75

Pigmented stones

Question 76

Tend to form when there is stasis of bile, impaired gallbladder motility, and an imbalance in the bile content

Answer 76

Gallstones

Question 77

(1) certain genetic factors, including LITH genes, (2) hepatic hypersecretion of biliary cholesterol, (3) gallbladder hypomotility, (4) rapid phase transitions of cholesterol in bile from liquid to solid state, and (5) certain intestinal factors Are factors that result in

Answer 77

Cholesterol stones

Question 78

Certain genetic factors such as LITH genes increase risk for

Answer 78

Cholesterol stones

Question 79

Normally, a delicate balance exists between the levels of

Answer 79

Bile acids, phospholipids, and cholesterol

Question 80

When this balance is disrupted, especially when there is supersaturation with cholesterol, there is predisposition for the development of

Answer 80

Cholesterol gallstones

Question 81

This is because when cholesterol supersaturates, it tends to

Answer 81

Crystallize

Question 82

In Admirand's Triangle. The small, blue area is the only area where cholesterol is

Answer 82

Completely soluble

Question 83

Refers to the blockage of any duct that carries bile from the liver to the gallbladder or from the gallbladder to the small intestine

Answer 83

Bilary obstruction

Question 84

The clinical setting of cholestasis or failure of biliary flow may be due to biliary obstruction by mechanical means or by metabolic factors in the

Answer 84

Hepatic cells

Question 85

Common to both obstructive and non obstructive cholestasis is the accumulation of bile pigment within the

Answer 85

Hepatic Parenchyma

Question 86

Elongated green-brown plugs of bile are visible in dilated bile canaliculi. Rupture of canaliculi leads to extravasation of bile, which is quickly phagocytosed by

Answer 86

Kupffer cells

Question 87

Droplets of bile pigment also accumulate within hepatocytes, which can take on a fine, foamy appearance, so called

Answer 87

"Feathery degeneration"

Question 88

Bile deposits as conjugated bile plugs in the

Answer 88

Draining ductules

Question 89

Bind bile acids in the intestine, resulting in interruption of the reabsorption of bile acids (which is usually 90 percent efficient), thus promoting their excretion

Answer 89

Bile acid sequestrants (BAS or bile acid resins (BAR))

Question 90

Used in the treatment of hypercholesterolemia because the removal of bile acids relieves the inhibition on bile acid synthesis in the liver, thereby diverting additional cholesterol into that pathway

Answer 90

BAS and BAR

Question 91

The available bile acid sequestrants include

Answer 91

Cholestyramine, colestipol, and colesevelam

Question 92

Certain soluble fibers (psyllium, pectin, wheat dextrin, and oat products) reduce serum levels of

Answer 92

Cholesterol

Question 93

May interfere with micelle formation in the proximal small intestine, resulting in decreased absorption of cholesterol and fatty acids

Answer 93

Soluble fibers