Heme Iron and Bilirubin DSA (McCormick)

Question 1

Components of hemoglobin

Answer 1

Heme
ring structure with one Fe chelated in the center by 4 nitrogen atoms (Site of reversible oxygen attachment)

Globin proteins
two alpha
two beta

4 heme molecules attached to each of the four globin proteins

Question 2

Hemoglobin synthesis

Answer 2

occurs in immature red blood cells in the bone marrow
need:
1. adequate supply of Fe
2. normal heme synthesis (synthesized in mitochondria)
3. normal globin synthesis (in cytoplasmic ribosomes)

Question 3

where is heme synthesized?

Answer 3

mitochondria

Question 4

where is globin synthesized?

Answer 4

cytoplasmic ribosomes

Question 5

methemoglobin

Answer 5

if the Fe2+ is oxidized to Fe3+ then methemoglobin is formed and is incapable of binding oxygen

Question 6

methemoglobin reductase

Answer 6

converts methemoglobin back to hemoglobin

Question 7

heme iron

Answer 7

source: breakdown of myoglobin (meats) and hemoglobin (RBC’s)

Question 8

breakdown of heme iron

Answer 8

absorbed by duodenal epithelial via binding or exocytosis
heme oxygenase (inside cells) splits heme iron –> releases Fe3+, CO and biliverdin
biliverdin reduced to bilirubin
enterocytes convert Fe3+ to Fe2+
iron then handled same as nonheme iron

Question 9

Nonheme iron

Answer 9

dietary
may be either ferric or ferrous
absorbed at duodenal mucosa
Fe3+ converted to Fe2+ by Dcytb
Cotransported into cell by DMT1 with H+
Fe2+ moves into cell and binds to mobilferrin at basolateral membrane
Fe2+ exits the cell and binds to transferrin for transport to all body tissues

Question 10

Dcytb (ferric reductase)

Answer 10

reduces dietary Fe3+ to Fe2+ at the extracellular apical membrane

Question 11

DMT1

Answer 11

Contransports Fe2+ and H+ into cells

Question 12

Apoferritin

Answer 12

“iron buffer system”

takes up excess circulating iron for storage or release of iron when circulating levels are too low

Question 13

ferritin

Answer 13

the storage form of iron

usually deposited into the liver or reticuloendothelial system (RES)

Question 14

Hemoglobin A

Answer 14

2 alpha

2 beta

Question 15

Hemoglobin F

Answer 15

2 alpha

2 gamma

Question 16

Hemoglobin A2

Answer 16

2 alpha

2 delta

Question 17

Hepcidin

Answer 17

binds to ferroportin (receptor on the basolateral membrane) and results in reduction of dietary iron absorption
***loss of this protein (decreased expression) results in sever iron overload

Question 18

Three cell types that control iron homeostasis

Answer 18

Enterocytes (intestinal cells)
macrophages
Hepatocytes

Question 19

unconjugated bilirubin

Answer 19

water insoluble

produced in macrophages (in the RES) from old RBC’s

Question 20

ferroportin

Answer 20

on the basolateral membrane of intestinal cell
exports iron out of intestinal cell
expression of this is controlled by hepcidin

Question 21

after Fe2+ leaves the intestinal cell….

Answer 21

it is converted back into Fe3+ and binds to transferrin for transport to all body tissues

Question 22

HCP1

Answer 22

transports dietary heme iron (from the intestinal tract)

Question 23

heme oxygenase

Answer 23

inside the epithelial cells of the intestine this enzyme splits heme iron and releases free Fe3+

Question 24

Enterocytes in epithelial cells of intestine

Answer 24

convert Fe3+ from heme iron breakdown into Fe2+ which enters the same pool as nonheme iron

Question 25

Bilirubin

Answer 25

A breakdown product of the hemoglobin molecule liberated from dead RBC’s by the reticuloendothelial system

Question 26

UDPGT

Answer 26

converts unconjugated bilirubin to conjugated bilirubin in the liver (it does this by adding two glucronide molecules)

Question 27

conjugated bilirubin

Answer 27

water soluble, produced in hepatocytes

leaves hepatocytes and enters bile canaliculi for active secretion into the intestinal tract

Question 28

fate of conjugated bilirubin after it leaves the liver??

Answer 28

1) enters intestinal tract–> where intestinal bacteria degrade it to urobilinogen and urobilin
2) a small part of the urobilinogen is metabolized to stercobilin (AKA why poop is brown)
3) some urobilinogen is reabosrbed by the gut
to either go to the kidneys to make urobilin or is re-excreted by the liver

Question 29

hyperbilirubinemia

Answer 29

causes urinary urobilinogen to be elevated

Question 30

Hepatocellular disease or biliary obstruction

Answer 30

bilirubin is not excreted from the liver–> accumulation in the serum –> leads to jaundice

Question 31

increased urinary bilirubin

Answer 31

happens when there is an increase in serum conjugated bilirubin

Question 32

Phototherapy for jaundice infants

Answer 32

Unconjugated bilirubin can be converted from the trans to the cis form by light
** cis form more easily excreted in urine **

Question 33

jaundice of newborn

Answer 33

most often caused by UDPGT malfunction, so there is a buildup of unconjugated bilirubin in the serum