Billirubin and haem

Question 1

what are bile pigments formed from

Answer 1

Bile pigments are substances formed from the haem portion of haemoglobin when old/damaged erythrocytes are broken down in the spleen and liver

Question 2

what is the predominant bile pigment

what extracts this

Answer 2

The predominant bile pigment is bilirubin, which is extracted from the blood by the hepatocytes and actively secreted into bile

Question 3

what color is bilirubin

Answer 3

Bilirubin is yellow and contributes to the colour of bile

Question 4

When erythrocytes are old/damaged they are broken down by

Answer 4

macrophages(which are phagocytic)

Question 5

where does the breaking down of old/damages erthyrocytes occur

Answer 5

This occurs mainly in the spleen & bone marrow but can also occur in the kupffer cells (resident macrophages) of the liver

Question 6

BILIRUBIN METABOLISM 1

what happens to erythrocytes

Answer 6

Red blood cell/erythrocytes is ingested into macrophage

Haemoglobin is broken down into; haem & globin

Question 7

BILIRUBIN METABOLISM 2

what happens to the haem broken down by macrophages

Answer 7

Haem is further broken down, under the action of the enzyme hemoxygenase into biliverdin and Fe2+ & CO

Question 8

BILIRUBIN METABOLISM

what happens to the globin broken down by macrophages

Answer 8

Globin (a protein) is broken down into amino acids which can then be used to generate new erythrocytes in the bone marrow

Question 9

BILIRUBIN METABOLISM 3

What happens to the products of haem break down (2)

Answer 9

The Fe2+ bound to the iron transporter transferrin is then shuttled to the bone marrow, to be incorporated into new erythrocytes

Biliverdin in reduced under the action of biliverdin reductase into unconjugated bilirubin

Question 10

BILIRUBIN METABOLISM 4

what happens when biliverdin is reduced into unconjugated bilirubin

Answer 10

Unconjugated bilirubin is toxic and must be excreted, it is lipid soluble and thus insoluble in the blood

Unconjugated bilirubin is bound to albumin and then transported to the liver

Question 11

BILIRUBIN METABOLISM 5

what happens to unconjugated bilirubin in the liver

Answer 11

Here it undergoes glucuronidation (essentially the addition of a glucuronic acid - in order to make it soluble to be excreted, similar to xenobiotic metabolism) under the action of the enzyme UDP Glucuronyl Transferase which converts it into conjugated bilirubin

Question 12

BILIRUBIN METABOLISM 6

What happens to the conjugated bilirubin produced in the liver

Answer 12

The conjugated bilirubin is then able to be dissolved in bile and can then travel down the right & left hepatic ducts, into the common hepatic duct, into the cystic duct to store in the gallbladder, but also into the common bile duct where it can then enter the duodenum

Question 13

BILIRUBIN METABOLISM 7

Where does the conjugated bilirubin travel in the small intestine to

Answer 13

The conjugated bilirubin travels to the small intestine until it reaches the ileum or the beginning of the large intestine where under the action of intestinal bacteria it is reduced through a hydrolysis reaction (a glucuronic acid group is removed) forming urobilinogen

Question 14

BILIRUBIN METABOLISM 8

What happens to urobilinogen

Answer 14

Urobilinogen is lipid soluble, around 10% is reabsorbed into the blood and bound to albumin and transported back to the liver - urobilinogen oxidised to urobilin

Question 15

BILIRUBIN METABOLISM 9

what happens to the urobilinogen which is transported back to the liver

Answer 15

Here it is either re-cycled into bile or transported into the kidneys where it is excreted in urine - responsible for the yellowish colour of urine

Question 16

BILIRUBIN METABOLISM 10

What happens to the urobilinogen which is not transported back to the liver

Answer 16

The remaining 90% of urobilinogen is oxidised by a different type of intestinal bacteria to form stercobilin

Question 17

BILIRUBIN METABOLISM 11

What happens to stercobilin

Answer 17

Stercobilin is then excreted into the faeces - responsible for its brownish colour

Question 18

What enzyme breaks down haem into biliverdin and Fe2+ & CO

Answer 18

enzyme hemoxygenase

Question 19

What enzyme reduces biliverdin into ungonjugated bilirubin

Answer 19

biliverdin reductase

Question 20

what is glucuronidation

Answer 20

essentially the addition of a glucuronic acid - in order to make unconjugated bilirubin soluble to be excreted

Question 21

What enzyme is responsible for the glucuronidation of unconjugated bilirubin into bilirubin

Answer 21

enzyme UDP Glucuronyl Transferase

Question 22

What happens to bilirubin when it reaches the end of the small intestine

Answer 22

under the action of intestinal bacteria it is reduced through a hydrolysis reaction (a glucuronic acid group is removed) forming urobilinogen

Question 23

What reaction does urobilinogen undergo in order to from stercobilin

Answer 23

oxidation