28. Heme Metabolism

Question 1

cyclic compound formed by linkage of 4 pyrrole rings through methyne bridges

Answer 1

porphyrins

Question 2

heme containing enzymes

Answer 2

catalase
peroxidase
guanylate cyclase

Question 3

Steps in heme synthesis

Answer 3

1. formation of delta-aminolevulinic acid (ALA synthase)
2. formation of porphobilinogen (ALA dehydrase)
3. formation of linear tetrapyrrole (Porphobilinogen deaminase)
4. formation of uroporphyrinogen III
5. formation of protoporphyrinogen IX - occurs in the cytosol, transferred back to mitochondria
6. protoporphyrinogen IX converted to protoporphyrin IX
7. addition of iron to protoporphyrin IX by ferrochelatase –> Heme

Question 4

rate limiting step of heme synthesis

enzyme and co-factor

Answer 4

formation of delta-aminolevulinic acid

•Glycine + Succinyl coa –> delta aminolevulinic acid

enz: ALA synthase
co-factor: pyridoxine

Question 5

formation of porphobilinogen involves

Answer 5

condensation of 2 ALA by zinc-containing ALA dehydratase

Question 6

formation of porphobilinogen is inhibited by

Answer 6

heavy metal ions e.g. lead that replace zinc

Question 7

ferrochelatase is inhibited by

Answer 7

lead

Question 8

introduction of iron into protoporphyrin IX occurs spontaneously, enhanced by

Answer 8

ferrochelatase

Question 9

steps in heme degradation

Answer 9

1. formation of bilirubin
2. uptake of bilirubin by the liver
3. formation of bilirubin diglucoronide
4. secretion of bilirubin into bile
5. formation of urobilins in the intestine

Question 10

formation of bilirubin

Answer 10

Heme –> biliberdin –> bilirubin

Enzyme: Heme oxygenase system

Question 11

after 120 days , RBC are taken up and degraded by

Answer 11

reticulendothelial system (liver, spleen)

Question 12

bilirubin is transported to the liver in the blood by binding to this protein

Answer 12

albumin

Question 13

in the liver, bilirubin binds to this intracellular protein

Answer 13

ligandin

Question 14

this enzyme is deficienct in
Crigler-Najjar I and II
Gilbert syndrome

Answer 14

Bilirubin glucuronyltransferase

Question 15

this form of bilirubin is transported into bile canaliculi and then into the bile

Answer 15

bilirubin diglucuronide

Question 16

in the intestine,

bilirubin –>

Answer 16

urobilinogen (colorless)

+ intestinal bacteria oxidize urobilinogen –> stercolin (brown)

Question 17

some urobilinogen is transported by the blood to

Answer 17

• reabsorbed to the portal circulation

* kidne -> urobilin (yellow) -> excreted

Question 18

lead inactivates these enzymes in heme synthesis

Answer 18

ALA dehydratase

ferrochelatase

Question 19

clinical presentation of lead poisoning

Answer 19

•ÎÎ urinary ALA and free erythrocyte porphyrins
*microcytic, hypochromic anemia with basophilic stippling of RBCs
•headache, memory loss
•peripheral neuropathy, claw hand, wrist-drop
•nausea, abdominal pain, diarhea
•lead lines in gums
•lead deposits in epiphyses

Question 20

genetic or acquired disorders due to abnormalities in the pathway of biosynthesis of heme, which result in accumulation and ÎÎ excretion of porphyrins or porphyrin precursors

Answer 20

porphyrias

Question 21

most common porphyria

Answer 21

porphyria cutanea tarda

Question 22

clinical presentation of porphyria

Answer 22

photosensitivity
neuropsychiatric symptoms
abdominal pain

Question 23

results from elevated level of plasma bilirubin

Answer 23

jaundice

Question 24

the causes of jaundice can be distinguished as

Answer 24

• prehepatic
• hepatic
• posthepatic

Question 25

used to measure bilirubin in serum

Answer 25

Van den Bergh reaction

Question 26

measures direct bilirubin

Answer 26

assay with no methanol

Question 27

measures total bilirubin

Answer 27

assay with methanol

Question 28

Heme synthesis takes place in the

Answer 28

* cytosol and mitochondria of | * liver and bone marrow

Question 29

substrates of heme synthesis

Answer 29

succinyl A coa; glycine; Fe2+

Question 30

ALA synthase is inhibited by

Answer 30

high levels of hemin (heme derivative)

Question 31

substrates of heme degradation

Answer 31

* Hme * NADPH * 2 UDP-glucuronic acid

Question 32

Product of heme synthesis

Answer 32

* urobilinogen - excreted in urine * stercobilin- excreted inf feces * CO * Fe2+

Question 33

heme degradation begins

Answer 33

spleen - macrophages

Question 34

globin is recycled into

Answer 34

amino acids •catabolized as intermediates of –citric acid cycle –fatty acid oxidation

Question 35

1. Heme ring is opened by

Answer 35

oxidation; heme oxygenase Heme –> Bilverdin (green pigment) + Fe3 + CO

Question 36

2. formation of bilirubin

Answer 36

•second bridging methylene is reduced Biliverdin –> bilirubin (red-orange) –> albumin –> liver enz. biliverdin reductase

Question 37

in the liver, bilirubin is

Answer 37

conjugated with glucuronate by bilirubin glucuronyl transferase

Question 38

Free heme concentration greater than 1 micro M can be toxic because

Answer 38

it catalyzes the production of reactive oxygen species

Question 39

CO from heme degradation functions as

Answer 39

cellular messenger | vasodilator