Heme Synthesis and Breakdown

Question 1

Where does the biosynthesis of heme primarily occur?

Answer 1

liver and erythroid cells of bone marrow

Question 2

Locations of heme synthesis

Answer 2

phase 1: mitochondria
phase 2: cytosol
phase 3: mitochondria

Question 3

ALA dehydratase inactivated

Answer 3

ALA accumulates

Question 4

Ferrochelatase inactivated

Answer 4

Protoporphyrin IX accumulates

Question 5

Lead Poisoning

Answer 5

ALA dehydratase and ferrochelatase inactivated; anemia, energy production down, neurologic symptoms (ALA), and heme production down

Question 6

Inherited metabolic disorders due to defects in heme synthesis; acute hepatic causes neurological symptoms, and erythropoietic causes skin and photosensitivity

Answer 6

Porphyrias

Question 7

Porphobilinogen (PBG) deaminase (liver) defect; overproduction of ALA and PBG; abdominal pain and neurological symptoms

Answer 7

Acute Intermittent Porphyria

Question 8

Uroporphyrinogen III Cosynthase (erythrocytes) defect; autosomal recessive; red-colored (from O2 oxidation) product uroporphyrin I; photosensitivity, red urine/teeth, and hemolytic anemia

Answer 8

Congenital Erythropoietic Porphyria

Question 9

Uroporphyrinogen Decarboxylase (liver and erythrocytes) defect; accumulation of uroporphyrnigon III which converts to uroporphyrnigen I and its oxidation products; photosensitivity of skin and bull skin, wind-red urine (USA)

Answer 9

Porphyria Cutanea Tarda (PCT)

Question 10

Protophyrinogen IX Oxidase (hepatic) defect; photosensitivity, neurologic symptoms, and developmental delay in children (King George III)

Answer 10

Variegate Porphyria

Question 11

Removes bridge between pyrrole rings of heme; requires O2 and releases CO; iron is oxidized to Fe3+ and Biliverdin is synthesized

Answer 11

Heme Oxygenase

Question 12

Conjugation of Bilirubin

Answer 12

BR/Albumin uptake by liver; UDP-glucuronic acid transferred to BR making BR-monoglucuronide and then diuronide; RATE LIMITING

Question 13

Phase 1 of heme synthesis

Answer 13

glycine and succinyl-CoA combine to form delta-aminolevulinic acid (ALA); uses ALA Synthase and B6 (pyridoxal phosphate)

Question 14

Heme synthesis pathway products

Answer 14

delta-ALA; porphobilinogen; hydroxymethylbilane; uroporphyrinogen III; coproporphyrinogen III; protoporphyrinogen IX; protoporphyrin IX; heme

Question 15

Heme degradation pathway

Answer 15

heme; biliverdin; bilirubin; albumin/bilirubin; bilirubin-monoglucuronide; bilirubin-diglucuronide; bilirubin; urobilinogen; urobilin or stercobilin