Heme Iron and Bilirubin DSA (McCormick)

Question 2

Components of hemoglobin

Answer 2

Hemering structure with one Fe chelated in the center by 4 nitrogen atoms (Site of reversible oxygen attachment)Globin proteinstwo alphatwo beta4 heme molecules attached to each of the four globin proteins

Question 3

Hemoglobin synthesis

Answer 3

occurs in immature red blood cells in the bone marrowneed:1. adequate supply of Fe2. normal heme synthesis (synthesized in mitochondria) 3. normal globin synthesis (in cytoplasmic ribosomes)

Question 4

where is heme synthesized?

Answer 4

mitochondria

Question 5

where is globin synthesized?

Answer 5

cytoplasmic ribosomes

Question 6

methemoglobin

Answer 6

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

Question 7

methemoglobin reductase

Answer 7

converts methemoglobin back to hemoglobin

Question 8

heme iron

Answer 8

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

Question 9

breakdown of heme iron

Answer 9

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

Question 10

Nonheme iron

Answer 10

dietary may be either ferric or ferrous absorbed at duodenal mucosaFe3+ converted to Fe2+ by DcytbCotransported into cell by DMT1 with H+Fe2+ moves into cell and binds to mobilferrin at basolateral membraneFe2+ exits the cell and binds to transferrin for transport to all body tissues

Question 11

Dcytb (ferric reductase)

Answer 11

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

Question 12

DMT1

Answer 12

Contransports Fe2+ and H+ into cells

Question 13

Apoferritin

Answer 13

“iron buffer system” takes up excess circulating iron for storage or release of iron when circulating levels are too low

Question 14

ferritin

Answer 14

the storage form of ironusually deposited into the liver or reticuloendothelial system (RES)

Question 15

Hemoglobin A

Answer 15

2 alpha2 beta

Question 16

Hemoglobin F

Answer 16

2 alpha2 gamma

Question 17

Hemoglobin A2

Answer 17

2 alpha2 delta

Question 18

Hepcidin

Answer 18

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 19

Three cell types that control iron homeostasis

Answer 19

Enterocytes (intestinal cells)macrophagesHepatocytes

Question 20

unconjugated bilirubin

Answer 20

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

Question 21

ferroportin

Answer 21

on the basolateral membrane of intestinal cellexports iron out of intestinal cellexpression of this is controlled by hepcidin

Question 22

after Fe2+ leaves the intestinal cell….

Answer 22

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

Question 23

HCP1

Answer 23

transports dietary heme iron (from the intestinal tract)

Question 24

heme oxygenase

Answer 24

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

Question 25

Enterocytes in epithelial cells of intestine

Answer 25

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

Question 26

Bilirubin

Answer 26

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

Question 27

UDPGT

Answer 27

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

Question 28

conjugated bilirubin

Answer 28

water soluble, produced in hepatocytes leaves hepatocytes and enters bile canaliculi for active secretion into the intestinal tract

Question 29

fate of conjugated bilirubin after it leaves the liver??

Answer 29

1) enters intestinal tract--> where intestinal bacteria degrade it to urobilinogen and urobilin2) a small part of the urobilinogen is metabolized to stercobilin (AKA why poop is brown)3) some urobilinogen is reabosrbed by the gutto either go to the kidneys to make urobilin or is re-excreted by the liver

Question 30

hyperbilirubinemia

Answer 30

causes urinary urobilinogen to be elevated

Question 31

Hepatocellular disease or biliary obstruction

Answer 31

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

Question 32

increased urinary bilirubin

Answer 32

happens when there is an increase in serum conjugated bilirubin

Question 33

Phototherapy for jaundice infants

Answer 33

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

Question 34

jaundice of newborn

Answer 34

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