Liver Biochemistry

Question 1

What is the makeup of the blood supply to the liver?

Answer 1

75% of the blood supply to the liver comes from the portal vein; 25% of the blood supply to the liver comes from the hepatic artery

Question 2

what is the biliary component made of?

Answer 2

bile ducts and the gallbladder

Question 3

what is the one way blood gets out of the liver?

Answer 3

blood flows out of the liver through 3 hepatic veins into a big vein called the inferior vena cava

Question 4

what is the main cell type found in the liver?

Answer 4

hepatocytes

Question 5

what is the main function of the hepatocytes?

Answer 5

they carry out most of the metabolic functions of the liver

Question 6

where are the endothelial cells of the liver found?

Answer 6

in the lining of the sinusoids

Question 7

how can the endothelial cells of the liver be characterized?

Answer 7

they present loosely, they have pores and fenestrations in the plasma membrane to allow exchange of material from the liver to the blood

Question 8

where are Kupffer cells found?

Answer 8

they are present in the lining of the sinusoids

Question 9

what are kupffer cells?

Answer 9

they are macrophages that protect the liver from gut-derived microbes, removed damageed/dead RBCs, and orchestrate an immune response by secreting cytokines

Question 10

what do the kupffer cells have?

Answer 10

a well-developed endocytic and phagocytic function and lots of lysosomes

Question 11

What are the hepatic stellate cells?

Answer 11

they are lipid-filled cells and they serve as the primary storage site for vitamin A

Question 12

what do the hepatic stellate cells control?

Answer 12

the turnover of hepatic connective tissue and extracellular matrix and regulate the contractility of the sinusoids

Question 13

what are pit cells?

Answer 13

liver associated lymphocytes or natural killer cells

Question 14

what is the function of pit cells?

Answer 14

they serve as a defense mechanism against the invasion of the liver by potentially toxic agents

Question 15

what are cholangiocytes and where are they found?

Answer 15

they line the bile ducts and they control bile flow rate and bile pH

Question 16

what blood proteins does the liver synthesize?

Answer 16

albumin, IgGs (antibodies), apoproteins, fibrinogen, prothrombin, blood clotting proteins and acute phase response proteins

Question 17

what are acute phase response proteins?

Answer 17

acute phase response encompasses all systemic changes in response to infection or inflammation

Question 18

what are two examples of acute phase response proteins?

Answer 18

C-reactive protein and protease inhibitors (alpha-1 Antitrypsin and alpha-1 antichymotrypsin)

Question 19

where does the arterial and venous blood mix in the liver?

Answer 19

in the sinusoids

Question 20

what features of the liver allow for greater access and increased contact between liver and blood?

Answer 20

lack of basement membrane and absence of tight junctions between hepatocytes and endothelial cells and fenestrations (pores) in the endothelial cell membrane

Question 21

what is bile made of?

Answer 21

bile acids, bile salts, and cholesterol

Question 22

what is the main function of bile acids and bile salts?

Answer 22

they emulsify fats so that they can be broken down and absorbed

Question 23

what are bile acids and salts known to be?

Answer 23

strong detergents; amphipathic- with polar and non-polar regions

Question 24

what are bile acids and salts synthesized from?

Answer 24

hepatic cholesterol

Question 25

where is bile made?

Answer 25

in hepatocytes

Question 26

where is bile released?

Answer 26

into bile canaliculi

Question 27

when is bile released into the duodenum?

Answer 27

in response to food

Question 28

what form is a bile acid in?

Answer 28

the protonated form (COOH)

Question 29

what form is bile salt in?

Answer 29

the de-protonated form (COO-)

Question 30

what surface of the bile salt molecule associates with the TAG?

Answer 30

the hydrophobic surface

Question 31

what surface of the bile salts faces outward, allowing the micelle to associate with pancreatic lipase/colipase?

Answer 31

the hydrophilic surface

Question 32

what is the rate limiting enzyme of the synthesis of bile acids?

Answer 32

7 alpha- hydroxylase

Question 33

what does 7 alpha-hydroxylase transform cholesterol into?

Answer 33

7 alpha-hydroxycholesterol (adds a hydroxyl group on the 7th position- so now there are 2 hydroxyl groups)

Question 34

where is the hydroxyl group positioned on cholesterol?

Answer 34

3rd position

Question 35

what happens when 7 alpha-hydroxycholesterol gets 1 COOH group added?

Answer 35

it becomes chenodeoxycholic acid

Question 36

what happens when 7 alpha hydroxycholesterol gets 1 COOH group and another OH group added?

Answer 36

it becomes cholic acid

Question 37

why do we need to conjugate?

Answer 37

by conjugating, you have increased the efficiency of the bile acid to emulsify

Question 38

what is pKa's association to efficiency of the bile acid to emulsify?

Answer 38

the lower the pKa, the more ionized the molecule, the better the detergent effect

Question 39

what happens to bile acids before secretion?

Answer 39

they are conjugated

Question 40

what are the primary bile acids?

Answer 40

cholic acid and chenodeoxycholic acid

Question 41

how many primary conjugated bile acids are there?

Answer 41

4

Question 42

how do you get the primary conjugated bile acid Glycocholic acid?

Answer 42

you add glycine to cholic acid

Question 43

how do you get the primary conjugated bile acid taurocholic acid?

Answer 43

you add taurine to cholic acid

Question 44

how do you get the primary conjugated bile acid Taurochenodeoxycholic acid?

Answer 44

you add taurine to chenodeoxycholic acid

Question 45

how do you get the primary conjugated bile acid glycochenodeoxycholic acid?

Answer 45

you add glycine to chenodeoxycholic acid

Question 46

how do you get secondary bile acids?

Answer 46

bacteria in the gut deconjugate and dehydroxylate primary bile salts

Question 47

what are the secondary bile acids?

Answer 47

deoxycholic acids and lithocholic acid

Question 48

what is an example of a medication used to treat hypercholesterolemia?

Answer 48

bile acid-binding resins

Question 49

what is an example of a bile acid-binding resin?

Answer 49

cholestyramine

Question 50

what effect does cholestyramine have?

Answer 50

they cause a large increase in secretion of bile acids, which in turn causes the rate of bile acid synthesis to be increased

Question 51

once the bile salts have done their jobs, what happens to them?

Answer 51

they are recycled back to the liver

Question 52

what happens when the rate of bile acid synthesis is increased?

Answer 52

there is depletion of the liver cholesterol pool, so there will be an increase in hepatic uptake of LDL from circulation--> lower plasma cholesterol levels

Question 53

what are gallstones?

Answer 53

crystals made up of bile supersaturated with cholesterol

Question 54

what is cholelithiasis?

Answer 54

insufficient secretion of bile salts into the gallbladder or excess cholesterol secretion into bile

Question 55

what does chronic disturbance in bile salt metabolism lead to?

Answer 55

malabsorption syndrome (steatorrhea) and deficiency in fat soluble vitamins

Question 56

the liver is the primary site for conversion and or degradation of what two things?

Answer 56

xenobiotics and/or metabolites

Question 57

what are xenobiotics?

Answer 57

compounds ingested from outside with no nutritional value/ potentially toxic

Question 58

what are metabolites?

Answer 58

compounds that are made in the body (intermediates and/or end products of metabolism)

Question 59

There are two phases to waste management. What do they entail?

Answer 59

first phase- polarity is increased. second phase- functional groups are conjugated to further increase polarity

Question 60

when the polarity of a compound is increased what happens?

Answer 60

it is easier to get rid of it (makes it more soluble)

Question 61

what are the phase I reactions catalyzed by?

Answer 61

cytochrome P450 (CYP) enzymes

Question 62

what happens in the phase one reactions and what do you get after them?

Answer 62

an oxygen is added to a xenobiotic or a waste metabolite- you get R-OH

Question 63

where are most drugs metabolized?

Answer 63

in the liver

Question 64

what does hepatic metabolism increase?

Answer 64

increases the hydrophilicity and hence their ability to be excreted

Question 65

hepatic metabolizing enzymes deal with infinite range of molecules that can be administered. How is this achieved?

Answer 65

by the responsible enzymes having low substrate specificity

Question 66

what is a characteristic of CYP?

Answer 66

they are a heme-containing protein present in the ER

Question 67

what do CYPs work with?

Answer 67

cytochrome P450 reductase (CYPR)

Question 68

Which CYP enzyme accounts for 30-40% of the CYP450 enzymes?

Answer 68

the CYP3A4 isoform

Question 69

how do CYPs operate?

Answer 69

via an electron transfer system

Question 70

the CYP protein is a heme containing protein that has iron in what form?

Answer 70

the ferric form

Question 71

what does the cytochrome P450 reductase provide as a releasing power?

Answer 71

NADPH

Question 72

Are CYPs present in high amounts in the liver?

Answer 72

no but they are induced by their substrates

Question 73

Agents that inhibit CYP will cause what?

Answer 73

increase in drug levels in the plasma

Question 74

agents that stimulate CYP will cause what?

Answer 74

decrease in drug levels in the plasma

Question 75

what is an example of a CYP inhibitor?

Answer 75

citrus juice

Question 76

what happens if a patient regularly takes their statins with a glass of grapefruit juice?

Answer 76

there will be an increase in statin levels in the plasma

Question 77

what is an example of a CYP inducer?

Answer 77

St. John's Wort

Question 78

what happens if a patient takes a statin and St. John's Wort?

Answer 78

there will be a decrease in statin levels in the plasma

Question 79

how is tylenol/acetaminophen eliminated?

Answer 79

it occurs via conjugation with glucuronic acid or sulfate

Question 80

what happens in acetaminophen overdose?

Answer 80

the capacity for normal conjugation is overwhelmed and it is oxidized by the liver CYP3A4 to NABQ1

Question 81

what is the NABQ1 detoxified by?

Answer 81

glutathione, but in acetaminophen overdose, the glutathione stores become depleted and the liver cells become damaged

Question 82

what can be given as an antidote to acetaminophen poisoning?

Answer 82

a sulphydryl compound called N-acetyl cysteine- it replenishes the glutathione

Question 83

what is the major change in all of the diseases of the liver?

Answer 83

the normally leaky basement membrane between endothelial cells and hepatocytes is replaced by high-density membrane containing fibrillar collagen

Question 84

what does increased stiffness of hepatic vascular channels offer?

Answer 84

resistance to free flow of blood through the liver, elevated intra-sinusoidal fluid pressure; portal hypertension

Question 85

what is the primary effect of all diseases of the liver?

Answer 85

impairment of free exchange of material between hepatocytes and blood