Heme Metabolism

Question 1

Porphyrins are cyclic compounds linked by how many pyrrole rings

Answer 1

4

Question 2

What links the pyrrole rings of porphyrin?

Answer 2

Methyne (-HC) bridges

Question 3

The intermediate steps in heme synthesis happens in ___

Answer 3

cytosol

Only the first and last three steps happen in the mitochondria

Question 4

What are the substrate for heme synthesis?

Answer 4

Succinyl-CoA + glycine

Question 5

Succinyl CoA and Glycine are converted to delta-aminolevulinic acid via the enzyme

Answer 5

delta-ALA syntase

Question 6

Acute intermittent porphyria is due to what enzyme deficiency

Answer 6

Hydroxymethylbilane synthase (uroporphyrinogen I synthase)

Question 7

Porphorea cutanea tarda is due to what enzyme deficiency

Answer 7

Uroporphyrinogen decarboxylase

Question 8

Cite the Heme Synthesis pathway

Answer 8

delta-ALA
Porphobilinogen
hydroxymethylbilane
Uroporphyrinogen III
Coproporphyrinogen III
Protopophyrinogen IX
Protoporphyrin IX
Heme

ALA Pa HO Ung Copy Para Pang Himas

Question 9

What is the rate limiting step in heme synthesis?

Answer 9

Conversion of

Succinyl-CoA + Glycine to dela aminolevulinic acid
Enzyme: ALA synthase
Co factor: Pyridoxine

Question 10

Which step in heme synthesis is inhibited by heavy metal ions

Answer 10

Formation of porphobilinogen

Since 2 molecules of ALA is created by the zinc-containing ALA dehydratase

Question 11

The first porphyrin is formed by ___

Answer 11

4 OBGs

Question 12

What is involved in the oxidation of iron?

Answer 12

ceruloplasmin

Question 13

What heavymetal inhibits ferrocheletase?

Answer 13

Lead

Question 14

[Diagnose]

increased urinary ALA< increased free erythrocyte porphyrine

Microcytic, hypochromic with basophilic stippling or RBC, headache, memory loss, wrist drop

Answer 14

Lead poisoning

Inhibits ALA dehydratase and ferrocheletase

Question 15

[Diagnose: poprhyria]

Cutaneous fragility, bilstering of the hands, forearms, and face

Answer 15

Porphyria cuteanea tarda

Question 16

[Diagnose: poprhyria]

abdominal pain, urine darkens on exposure to light

Answer 16

Acute intermitten porphyria

Question 17

What is released by the heme oxygenase system of the reticuloendothelial cells during heme degradation?

Answer 17

Carbon monoxide

Question 18

What transports bilirubin to the liver?

Answer 18

albumin

Question 19

Bilirubin binds to what intracellular protein in the body

Answer 19

ligandin

Question 20

What enzyme conjugates two molecules of glucoronic acid to bilirubin in the liver?

Answer 20

Bilirubin gluconyltransferase

Deficiency = high unconjucated

Criggler-Najjar, Gilbert

Question 21

In the gut, bilirubin so converted to a colorless substance called

Answer 21

urobilinogen

Question 22

Intestinal bacteria convert urobilinogen to brown compound called

Answer 22

Stercolin

Question 23

In the kidney, urobilinogen is converted to a yellow substance called

Answer 23

urobilin

Question 24

Van den Bergh reaction is used to measure what in the serum

Answer 24

bilirubin

Question 25

Example of congenital cause of direct bilirubinemia?

Answer 25

Direct = Dubin = Dubin and Rotor

Question 26

What component of hemoglobin is present in utero until adulthood?

Answer 26

Alpha

Alpha always, Gamma Goes, Becomes beta

Question 27

What are the components of your fetal hemoglobin?

Answer 27

2 alpha

2 gamma

Question 28

What anemi the AA changes in Sickle Cell Anemia?

Answer 28

Glu to Val

Remember, GLUe in SCA, sticking of hgb together

Question 29

What is the primary source of H+ that leads to displacement of O2 from Hgb in tissues

Answer 29

Carbonic acid

Question 30

What is the most serious complication of blood transfusion?

Answer 30

iron overload

1u pRBC = 250mg Fe