Week 16

Question 1

What is heme?

Answer 1

A metalloporphyrin containing Fe²⁺ in the center of protoporphyrin IX.

Question 2

Major functions of heme?

Answer 2

Component of hemoglobin, myoglobin, cytochromes, catalase, peroxidase, nitric oxide synthase.

Question 3

Main sites of heme synthesis?

Answer 3

Liver (cytochrome P450) and bone marrow (hemoglobin).

Question 4

Where does heme synthesis occur within the cell?

Answer 4

First step + last 3 steps in mitochondria; intermediate steps in cytosol.

Question 5

Rate-limiting and committed step of heme synthesis?

Answer 5

Formation of δ-aminolevulinic acid (ALA).

Question 6

Enzyme for ALA formation?

Answer 6

ALA synthase (ALAS).

Question 7

Substrates for ALA synthase?

Answer 7

Glycine + succinyl-CoA.

Question 8

Required cofactor for ALAS?

Answer 8

Pyridoxal phosphate (vitamin B6).

Question 9

How is hepatic ALAS1 regulated?

Answer 9

End-product inhibition by heme (hemin).

Question 10

Enzyme converting ALA → porphobilinogen?

Answer 10

ALA dehydratase (porphobilinogen synthase).

Question 11

Which toxin inhibits ALA dehydratase?

Answer 11

Lead.

Question 12

Product formed from four porphobilinogens?

Answer 12

Uroporphyrinogen III.

Question 13

Which porphyrin type is physiologically important in humans?

Answer 13

Type III.

Question 14

Final step of heme synthesis?

Answer 14

Insertion of Fe²⁺ into protoporphyrin IX by ferrochelatase.

Question 15

Which enzyme is inhibited by lead at the final step?

Answer 15

Ferrochelatase.

Question 16

Which two enzymes are inhibited by lead?

Answer 16

ALA dehydratase and ferrochelatase.

Question 17

What accumulates in lead poisoning?

Answer 17

ALA and protoporphyrin.

Question 18

Why is lead poisoning toxic?

Answer 18

Decreased heme synthesis + neurotoxicity from ALA accumulation.

Question 19

Hematologic effect of lead poisoning?

Answer 19

Anemia due to impaired heme production.

Question 20

What are porphyrias?

Answer 20

Disorders of heme synthesis causing accumulation of porphyrins or their precursors.

Question 21

How are porphyrias classified by tissue?

Answer 21

Hepatic or erythropoietic.

Question 22

How are porphyrias clinically classified?

Answer 22

Acute (neurovisceral) or cutaneous (photosensitive).

Question 23

Enzyme defects BEFORE tetrapyrrole formation cause what symptoms?

Answer 23

Neurovisceral symptoms.

Question 24

Enzyme defects AFTER tetrapyrrole formation cause what symptoms?

Answer 24

Photosensitivity and skin damage.

Question 25

Enzyme deficiency in AIP?

Answer 25

Porphobilinogen deaminase.

Question 26

Type of porphyria is AIP?

Answer 26

Acute hepatic porphyria.

Question 27

Main accumulated metabolites in AIP?

Answer 27

ALA and porphobilinogen.

Question 28

Why does AIP cause neurological symptoms?

Answer 28

ALA and PBG are neurotoxic.

Question 29

Classic symptoms of AIP?

Answer 29

Severe abdominal pain, neuropathy, psychiatric symptoms.

Question 30

Is photosensitivity present in AIP?

Answer 30

No.

Question 31

Common triggers of AIP attacks?

Answer 31

Drugs, fasting, alcohol, hormones.

Question 32

Enzyme deficiency in PCT?

Answer 32

Uroporphyrinogen decarboxylase.

Question 33

Type of porphyria is PCT?

Answer 33

Cutaneous hepatic porphyria.

Question 34

Major clinical feature of PCT?

Answer 34

Photosensitivity with blistering skin lesions.

Question 35

Why does photosensitivity occur in PCT?

Answer 35

Accumulated porphyrins generate reactive oxygen species in light.

Question 36

Neurological symptoms in PCT?

Answer 36

Absent.

Question 37

What percentage of heme comes from old RBCs?

Answer 37

~85%.

Question 38

Enzyme that converts heme → biliverdin?

Answer 38

Heme oxygenase.

Question 39

Products of heme oxygenase reaction?

Answer 39

Biliverdin, Fe³⁺, CO.

Question 40

Biliverdin is converted to what?

Answer 40

Bilirubin.

Question 41

How is bilirubin transported in blood?

Answer 41

Bound to albumin.

Question 42

Where does bilirubin conjugation occur?

Answer 42

In hepatocytes.

Question 43

Enzyme responsible for bilirubin conjugation?

Answer 43

Bilirubin glucuronyltransferase.

Question 44

What makes bilirubin water-soluble?

Answer 44

Conjugation with glucuronic acid.

Question 45

Conjugated bilirubin is excreted into where?

Answer 45

Bile.

Question 46

What gives stool its brown color?

Answer 46

Stercobilin.

Question 47

What gives urine its yellow color?

Answer 47

Urobilin.

Question 48

Unconjugated bilirubin is elevated in which conditions?

Answer 48

Hemolysis, impaired conjugation.

Question 49

Conjugated bilirubin is elevated in which conditions?

Answer 49

Biliary obstruction or impaired secretion.

Question 50

Can unconjugated bilirubin appear in urine?

Answer 50

No (albumin-bound).

Question 51

Does conjugated bilirubin appear in urine?

Answer 51

Yes.

Question 52

Cause of Gilbert syndrome?

Answer 52

Reduced bilirubin glucuronyltransferase activity.

Question 53

Type of hyperbilirubinemia in Gilbert syndrome?

Answer 53

Unconjugated.

Question 54

Clinical severity of Gilbert syndrome?

Answer 54

Mild and benign.

Question 55

Defect in Dubin–Johnson syndrome?

Answer 55

Impaired secretion of conjugated bilirubin into bile.

Question 56

Type of hyperbilirubinemia?

Answer 56

Conjugated.

Question 57

Liver appearance in Dubin–Johnson syndrome?

Answer 57

Black pigmented liver.

Question 58

Why is neonatal jaundice common?

Answer 58

Low activity of bilirubin glucuronyltransferase.

Question 59

Dangerous complication of neonatal jaundice?

Answer 59

Kernicterus.

Question 60

Why is unconjugated bilirubin toxic to the brain?

Answer 60

It can cross the immature blood–brain barrier.

Question 61

Treatment for neonatal jaundice?

Answer 61

Blue light phototherapy.

Question 62

How does phototherapy work?

Answer 62

Converts bilirubin into water-soluble photoisomers.

Question 63

Why do acute porphyrias cause neurological symptoms?

Answer 63

Accumulation of neurotoxic heme precursors.

Question 64

Why do cutaneous porphyrias cause photosensitivity?

Answer 64

Porphyrins generate ROS when exposed to light.

Question 65

Why does lead poisoning mimic porphyria?

Answer 65

It blocks key heme synthesis enzymes.