IHL I - Heme, Iron, and Bilirubin Metabolism (DSA)

Question 0

what is the heme portion of hemoglobin?

Answer 0

porphyrin ring with one iron chelated in the center by 4 nitrogen atoms

-site of reversible attachment for oxygen

Question 1

two major components of hemoglobin

Answer 1

heme and globin proteins

heme is only 3% of total molecule

Question 2

what is the globin portion of hemoglobin?

Answer 2

two pairs of globin chains (normal is two alpha/two beta)

- each globin has an associated heme group
- 4 hemes per hemoglobin (4 O2 binding sites per heme)
- 16 total O2 molecules per hemoglobin

Question 3

Where does hemoglobin synthesis occur?

Answer 3

in immature red blood cells in the bone marrow

- synthesis depends on three things:
	- adequate supply of Fe
	- normal heme synthesis
	- normal globin synthesis

Question 4

What state of iron can bind to hemoglobin?

Answer 4

Fe2+

- Fe3+ is in methemoglobin
	- due to drugs - nitrites or sulfonamides
- Fe3+ forms methemoglobin which cannot bind O2

Question 5

what is methemoglobin reductase?

Answer 5

enzyme in the erythrocyte that can convert methemoglobin to hemoglobin

Fe3+ > Fe2+

Question 6

Where is heme synthesized?

Answer 6

mitochondria of the erythrocyte

Question 7

Where is globin synthesized?

Answer 7

in cytoplasmic ribosomes of the erythrocyte

Question 8

What are the two major types of dietary Iron?

Answer 8

heme (breakdown of myoglobin and hemoglobin)

non-heme (dietary sources)

Question 9

Where is iron absorbed?

Answer 9

in the duodenum

-each is absorbed differently

Question 10

heme iron

Answer 10

from breakdown of hemoglobin and myoglobin

broken down by heme oxygenase inside the cell

Question 11

heme oxygenase

Answer 11

splits heme iron to free Fe3+, CO, and biliverdin

biliverdin - reduced to bilirubin

Question 12

Dcytb

Answer 12

ferric reductase

reduces dietary Fe3+ (nonheme) to Fe2+ so that it can be absorbed

Question 13

DMT

Answer 13

cotransporter of Fe2+ and H+

-brings nonheme iron into the epithelial of the duodenum

Question 14

which form of iron is absorbed in the duodenum?

Answer 14

Fe2+

Question 15

mobilferrin

Answer 15

binds to the absorbed dietary Fe2+ and transports it to the basolateral surface of the cell

Question 16

ferroportin (PF1)

Answer 16

transports Fe2+ across the basolateral membrane

-hephaestin then converts Fe2+ to Fe3+ so that it can be transported

Question 17

hephaestin

Answer 17

oxidized Fe2+ to Fe3+ so that it can be transported in the blood stream

Question 18

transferrin

Answer 18

binds Fe3+ for transport to all body tissues

-primary deposits in the liver and RES by binding to apoferritin to form ferritin

Question 19

apoferritin

Answer 19

binds to circulating iron and forms ferritin

Question 20

iron buffer system

Answer 20

apoferritin ability to bind to circulating iron

-helps to maintain a constant serum iron level

Question 21

hepcidin

Answer 21

secreted by hepatocytes and will downregulate the ferroportin transfer of iron at basolateral membrane

causes the ferroportin to be internailized and degraded

loss of function leads to severe iron overload

Question 22

what three cell types control iron homeostasis?

Answer 22

enterocytes, macrophage, hepatocytes

Question 23

location of ferroportin

Answer 23

enterocytes, macrophages, and hepatocytes
-cells involved in iron homeostasis

under the regulation of hepcidin
-systemic control of iron homeostasis

Question 24

enterocyte

Answer 24

intestinal absorptive cell

Question 25

bilirubin

Answer 25

breakdown product of hemoglobin by reticuloendothelial system

Question 26

what is the first step in hemoglobin breakdown?

Answer 26

macrophage breaks down hemoglobin to heme and globin
-heme is converted to biliverdin and iron

biliverdin converted to unconjugated or water-insoluble bilirubin

Question 27

bilirubin

Answer 27

unconjugated and water-insoluble

Question 28

where is unconjugated bilirubin found

Answer 28

secreted by macrophages after hemoglobin breakdown
-will bind to albumin and travel to hepatocytes

taken up by either passive diffusion or receptor-mediated endocytosis into the hepatocyte cells

Question 29

UDPGT

Answer 29

uridine 5’-diphosphate glucuronyl transferase

converts unconjugated bilirubin to conjugated bilirubin

occurs at the smooth ER of the hepatocyte

Question 30

reaction of UDPGT?

Answer 30

adds glucuronide to the unconjugated bilirubin

-forms the conjugated bilirubin (water-soluble)

Question 31

what is the fate of conjugated bilirubin?

Answer 31

will be delivered to the bile canaliculi for secretion into the intestinal tract

Question 32

glucuronic acid

Answer 32

combined with unconjugated bilirubin to form bilirubin glucoronide (conjugated, water-soluble form)

Question 33

how many glucuronide are added to bilirubin?

Answer 33

two!

Question 34

what happens to bilirubin after it is secreted into the intestines through the bile

Answer 34

intestinal bacteria degrade the conjugated bilirubin to urobilinogen and urobilin

Question 35

urobilinogen

Answer 35

in the intestines, bacteria degrade the conjugated bilirubin into urobilinogen

Question 36

stercobilin

Answer 36

the urobilinogen that makes its way to the colon is converted to stercobilin
-gives stool its pigment

Question 37

hyperbilirubinemia

Answer 37

elevated levels of urinary urobilinogen

Question 38

jaundice

Answer 38

accumulation of bilirubin in the serum

- conjugated bilirubin is water soluble and can be filtered by the glomerulus and excreted in urine
- increased urinary bilirubin occurs when there is an increase in the serum conjugated bilirubin