Biochemistry of the Liver

Question 1

What is the role of Cytochrome p450?

Answer 1

metabolises potentially toxic compounds, including drugs and products of endogenous metabolism such as bilirubin principally in the liver

Question 2

Roles of the liver?

Answer 2

First destination of most nutrients and xenobiotics absorbed from the GI tract
Bile production
Elimination of unwanted molecules
Secretion of plasma proteins
    e.g. albumin 
Storage of important molecules
    e.g. fuels, iron, vitamins
Regulation of metabolism
   carbohydrate and lipid metabolism - fuel storage
   amino acid metabolism - urea cycle

Question 3

How are proteins seperated by size?

Answer 3

Electrophoresis

Question 4

What are the main functions of plasma proteins?

Answer 4

Maintenance of oncotic or colloid osmotic pressure
- don’t exit into interstitial fluid
- prevents loss of plasma proteins
Transport of hydrophobic substances
- steroid hormones, free fatty acids, bilirubin, cholesterol
pH buffering
- amino acid side chains can carry net charges
Enzymatic
- e.g. blood clotting
Immunity

Question 5

How does the oncotic force act?

Answer 5

draws fluid from body compartments to the blood

Question 6

What controls oncotic pressure?

Answer 6

Albumin

Question 7

What is the role of alpha gobulin?

Answer 7

transport lipoproteins, lipids, hormones and bilirubin
retinol binding protein - ceruloplasmin
- transports vitamin A

Question 8

What does vitamin A deficiency result in?

Answer 8

visual impairment

lipid soluble alcohol, converted to retinaldehyde, part of rhodopsin, a visual pigment

Question 9

Name two types of beta gobulins?

Answer 9

transferrin

• transports Fe3+
• indicator of iron deficiency

fibrinogen

• inactive form of fibrin
• clotting of blood

Question 10

What is the most abundant plasma protein?

Answer 10

Albumin

Question 11

How much Albumin does the liver normally make each day?

Answer 11

14 g/day

Question 12

What stimulates Albumin production? What can cause it to drop?

Answer 12

insulin stimulates production

starvation/low protein diet causes decrease of levels - levels are low in liver disease

Question 13

Which endogenous and exogenous substances does Albumin transport?

Answer 13

transports important endogenous lipophilic substances e.g. fatty acids, distribution of energy-rich substrates, bilirubin, breakdown product of haem, thyroid hormones

transports important exogenous substances e.g.
drugs like aspirin (any drug that has a weak hydrophobic capacity)

Question 14

Describe the transport mechanisms of Albumin?

Answer 14

Multiple binding sites for hydrophobic molecules
hydrophobic clefts in globular domains
low affinity, but high capacity because of high concentration
Transports endogenous and exogenous substances

Question 15

How is iron transported?

Answer 15

as ferric ion Fe3+

bound to transferrin

Question 16

How is iron stored in cells?

Answer 16

bound to ferritin

Question 17

How is copper transported in the blood?

Answer 17

bound to ceruloplasmin

Question 18

What is Wilson’s Disease?

Answer 18

Copper deficiency

Question 19

Are Steroid hormones and the T3/T4 thyroid hormones hydrophobic or hydrophillic?

Answer 19

hydrophobic

Question 20

How is thyroxine transported in the blood?

Answer 20

bound to thyroid-binding globulin

Question 21

How is cortisol transported in the blood?

Answer 21

bound to cortisol-binding globulin

Question 22

Describe the make up of lipoproteins?

Answer 22

Core of hydrophobic lipids
     cholesterol esters
     triglycerides
Surrounded by shell
      polar lipids (phospholipids)
      apoproteins
Free cholesterol dispersed throughout

Question 23

What is the function of HDL?

Answer 23

Removes excess cholesterol from cells

• cholesterol is esterified with fatty acids
• transported back to liver
• excreted as bile salts via biliary system or faeces

Question 24

Which organ can control cholesterol levels?

Answer 24

liver

Question 25

What is cholesterol a precursor of?

Answer 25

bile acids steroid hormones vitamin D

Question 26

What is cholesterol metabolism important for?

Answer 26

etiology of cardiovascular disease | major component of gall stones

Question 27

Where is cholesterol stored?

Answer 27

lipid droplets

Question 28

How is cholesterol transported in water?

Answer 28

30 % of circulating cholesterol is in free form Majority is esterified to a wide range of long-chain fatty acids - through hydroxyl group - even less soluble in water

Question 29

How is cholesterol solubilised?

Answer 29

is incorporated into lipoproteins

Question 30

Where is the main and lesser sites of cholesterol synthesis?

Answer 30

1. liver | Lesser: intestine, adrenal cortex, gonads

Question 31

What does the synthesis of 1 mol cholesterol require?

Answer 31

``` source of C atoms 18 mol of acetyl-CoA source of reducing power 16 mol of NADPH significant amounts of energy 36 mol of ATP ```

Question 32

What is the role of HMG-CoA reductase?

Answer 32

Catalyses the irreversible formation of mevalonic acid

Question 33

What reduces HMG-CoA reductase activtiy?

Answer 33

Dietary cholesterol and high intrahepatocyte cholesterol

Question 34

What stimulates HMG-CoA reductase activity?

Answer 34

fasting

Question 35

What is the most abundant form of vitamin D in the circulatory system?

Answer 35

Vitamin D3

Question 36

What is the role of vitamin D?

Answer 36

regulation of calcium and phosphorus metabolism

Question 37

What are the three groups of steroid hormones?

Answer 37

corticosteroids androgens estrogens

Question 38

Where are corticosteroids, androgens and estrogens released?

Answer 38

corticosteroids - adrenal cortex androgens - testis estrogens - ovary

Question 39

How are primary bile salts converted to secondary bile salts?

Answer 39

bacteria in the intestine

Question 40

Describe the life cycle of bile salts?

Answer 40

Synthesised and secreted by liver Stored as component of bile in the gall bladder Once released into the duodenum, act as detergents for emulsifying ingested lipids Recycled by enterohepatic circulation

Question 41

How is cholesterol excretion manipulated?

Answer 41

Anion exchange resins (e.g. cholestyramine) bind bile salts and inhibit reabsorption in the enterohepatic circulation Increased bile salt excretion and synthesis of bile salts Concentration of cholesterol in the liver is decreased The number of LDL receptors of hepatic cells increases Uptake of LDL cholesterol from plasma increases Lower plasma LDL and therefore cholesterol