Lecture 14: Liver Biochemistry

Question 1

How are liver lobes subdivided?

Answer 1

Multiple lobes

Sinusoids

Question 2

Describe the liver’s blood supply.

Answer 2

Portal Vein: nutrient-rich blood from bowel (75%)
-enteric circulation

Hepatic Artery: oxygen-rich blood (25%)
-peripheral circulation

Question 3

What makes up the biliary component of the liver?

Answer 3

Bile ducts

Gallbladder

Question 4

Through what structure does blood flow out from the liver?

Answer 4

Inferior Vena Cava

-composed of 3 hepatic veins

Question 5

What is the function of endothelial cells in the liver?

Answer 5

Allows exchange of materials between sinusoids and hepatocytes

Question 6

What is the role of hepatocytes?

Answer 6

Carry out most of the metabolic functions of the liver

Question 7

What is the role of Kupffer Cells?

Answer 7

Macrophages in the liver

• found in lining of sinusoids
• protect liver from gut derived microbes
• removes damaged/dead RBC
• role in immune response
• endocytic and phagocytic functions

Question 8

What is the role of hepatic stellate cells?

Answer 8

Storage site for Vitamin A and other lipids

Question 9

What is the role of pit cells?

Answer 9

Lymphocytes

-NK cells: protects against viruses and tumor cells

Question 10

What is the role of cholangiocytes?

Answer 10

• Line bile ducts

- Control bile flow rate and bile pH

Question 11

What blood proteins does the liver synthesize?

Answer 11

• Albumin
• Antibodies
• Apoproteins (lipid transport)
• Fibrinogen
• Prothrombin
• Blood Coagulation Factors
• Acute Phase Response Proteins

Question 12

What is the role of bile salts and acids?

Answer 12

Emulsification of fats
Absorption of fat soluble vitamins
Digestion and absorption of fats
Prevention of cholesterol precipitation 
Elimination of cholesterol

Question 13

Where is bile made and stored?

Answer 13

Made in hepatocytes

Released into bile canaliculi to be stored in gallbladder

Question 14

What is the difference between a bile acid and bile salt?

Answer 14

Bile acid: Protonated form (COOH)

Bile salt: Deprotonated form (COO-)

Question 15

What is the committed step in the synthesis of bile acids?

Answer 15

Cholesterol ——–> 7α-hydroxycholesterol
Enzyme: 7α-hydroxylase

Takes place in ER of hepatocytes

Question 16

What are the two common bile acids?

Answer 16

Cholic Acids: 3 OH groups

Chenodeoxycholic Acids: 2 OH groups

Question 17

In the presence of taurine, what does cholic acid become?

Answer 17

Taurocholic Acid

Question 18

In the presence of glycine, what does cholic acid become?

Answer 18

Glycocholic Acid

Question 19

In the presence of taurine, what does chenodeoxycholic acid become?

Answer 19

Taurochenodeoxycholic Acid

Question 20

In the presence of glycine, what does chenodeoxycholic acid become?

Answer 20

Glycochenodeoxycholic Acid

Question 21

What is the role of primary bile salts?

Answer 21

Used in the duodenum to emulsify dietary lipids to aid in their digestion and absorption

Question 22

What is the secondary bile acid derived from cholic acid?

Answer 22

Deoxycholic acid

Question 23

What is the secondary bile acid derived from chenodeoxycholic acid?

Answer 23

Lithocholic acid

Question 24

How are secondary bile acids formed?

Answer 24

Bacteria deconjugate primary bile salts into secondary bile salts
-absorbed by ileum and either excreted (5%) or recycled back into liver (95%) via enterohepatic circulation

Question 25

What resin can cause a larger increase in excretion of bile acids and help lower cholesterol levels?

Answer 25

Cholestyramine | -also increases rate of bile synthesis

Question 26

What are gallstones?

Answer 26

Crystals made up of bile supersaturated with cholesterol

Question 27

What is cholelithiasis?

Answer 27

Presence of one or more gallstones in the gallbladder | -due to insufficient secretion of bile salts or phospholipids into gallbladder or excess secretion into bile

Question 28

What are metabolites?

Answer 28

Compounds made in body - intermediates - end products of metabolism

Question 29

What are xenobiotics?

Answer 29

Compounds ingested from outside that have no nutritional value - pharmacological agents - recreational drugs - food additives

Question 30

What happens in Phase I of the inactivation and detoxification of xenobiotics?

Answer 30

Polarity is increased to make xenobiotic more soluble - reduction - oxidation - hydroxylation - hydrolysis

Question 31

What catalyzes Phase I of the inactivation and detoxification of xenobiotics?

Answer 31

Cytochrome P450 | -mostly CYP1, CYP2, CYP3

Question 32

What happens in Phase II of the inactivation and detoxification of xenobiotics?

Answer 32

Functional groups are conjugated for safe excretion - conjugation - sulfation - methylation - glucuronidation

Question 33

Describe the process of drug metabolism.

Answer 33

In the liver, metabolites will have increased hydrophilicity in order to be excreted and less pharmacologically active. -most drugs

Question 34

Agents that inhibit CYP will cause an ____ in drug levels in plasma.

Answer 34

Agents that inhibit CYP will cause an INCREASE in drug levels in plasma.

Question 35

Agents that stimulate CYP will cause a ____ in drug levels in plasma.

Answer 35

Agents that stimulate CYP will cause a DECREASE in drug levels in plasma.

Question 36

What are examples of CYP inhibitors?

Answer 36

Citrus and grapefruit juices Itraconazole Clarithromycin Cyclosporine

Question 37

What are examples of CYP inducers?

Answer 37

St John's Wort Rifampicin Carbamazepine

Question 38

What are ALT and AST involved in?

Answer 38

Interconversion of amino acids and keto acids required for protein and carbohydrate metabolism

Question 39

Why are elevated ALT and AST levels dangerous?

Answer 39

Indicates liver disease since these enzymes are released from damaged hepatocytes