Metabolism of porphyrins and bile pigments

Question 1

Porphyrins

Answer 1

cyclic compound that bind metal ions

Question 2

Heme as prothetic group

Answer 2

Protoporhyrin 9 + Fe2+ -> heme

• hemoglobin, myoglobin
• cytochromes
• catalase, peroxidase
• nitric oxide synthase

Question 3

Myoglobin

Answer 3

monomer
proximal + distal His
globin: 8 alpha-helical domains and linker sequence

Question 4

Hemoglobin

Answer 4

tetramer
alpha2beta2, 4O2
2,3 BPG
positive cooperativity
sigmoidal saturation curve

Question 5

1.Succinyl CoA + Glycine -> ALA

Answer 5

-CoASH
-CO2
enzyme: ALA SYNTHASE
Rate limiting
requires PLP

Question 6

2. 2ALA -> Porphobilinogen

Answer 6

-2 H20
enzyme: ALA DEHYDRATASE
contains Zn2+
inhibited by lead

Question 7

3. 4 Porphobilinogen -> Hydroxymethylbilane

Answer 7

• 4 NH3

enzyme: PORPHOBILIOGEN DEAMINASE

Question 8

4. Hydroxymethylbilane -> Uroporphyrinogen 3

Answer 8

enzyme: UROPORPHYRINOGEN 3 SYNTHASE

Question 9

5. Uroporphyrinogen 3 -> Coproporphyrinogen 3

Answer 9

• 4 CO2

enzyme: UROPORPHYRINOGEN DECARBOXYLASE

Question 10

6. Coproporphyrinogen 3 -> Protoporphyrinogen 9

Answer 10

• 2 CO2
• 4 H
  enzyme: COPROPORPHYRINOGEN 3 OXIDASE

Question 11

7. Protoporphyrinogen 9 -> Protoporphyrin 9

Answer 11

• 6H

enzyme: PROTOPORPHYRINOGEN OXIDASE

Question 12

8. Protoporphyrin 9 -> heme

Answer 12

+Fe2+
enzyme: FERROCHELATASE
inhibited by lead

Question 13

ALAS-L

Answer 13

Ala synthase
liver specific
heme inhibits transcription, mRNA export, mitochondrial uptake, enzymatic activity

Question 14

ALAS -E

Answer 14

Ala synthase
erythroid specific
deficiency: sideroblastic anemia
heme inhibits iron release from ferritin, stimulates global production
epo stimulates transcription

Question 15

Porphyria

Answer 15

symptoms: photosensivity, neuropsychiatric symptoms, fluorescent teeth, red urine
diagnosis: assay of enzymatic activities in RBC, analysis of urine
treatment: administration of hemin, sunscreen, carotenoids, no drugs or alcohol

Question 16

Breakdown of heme

Answer 16

Heme - HEME OXYGENASE - biliberdin - BILIVERDIN REDUCTASE - bilirubin

Question 17

Bilirubin excretion

Answer 17

formation in monocyte system - bound to albumin in blood - hepatocyte uptake - conjugated with glucuronic acid - excretion to bile canaliculi - bacterial beconjugation in colon - 10% reabsorbed and excreted in urine - 90% as faces

Question 18

Hyperbilirubinemia

Answer 18

1. indirect:
   - indirect-reaction bilirubin: methanol soluble
   - prehepatic, hepatic jaundice
2. direct
   - direct-reacting bilirubin: water soluble
   - posthepatic jaundice

Question 19

Prehepatic jaundice

Answer 19

1. Homolytic anemias
2. Neonatal jaundice
3. Hyperbilirubinemic toxic encephalopathy

Question 20

Hepatic jaundice

Answer 20

1. Crigler-Najjar syndrome 1
   - UDP-glucuronosyl transferase deficiency, fatal, phototherapy
2. Crigler-Najjar syndrom 2
   - partial enzyme defect, phenobarbital
3. Gilberts disease
4. Toxic hyperbilirubinemia

Question 21

Posthepatic jaundice

Answer 21

1. Obstruction of biliary tree

2. Dubin-Johnson and Rotor syndrome