Heme Synthesis and Breakdown

Question 1

Which porphyrias are hepatic?

Answer 1

acute intermittent

variegate

Question 2

What happens to BR levels in hepatitis?

Answer 2

Increased levels of unconjugated and conjugated BR

Question 3

What enzyme does Heme inhibit?

Answer 3

ALA synthase (first enzyme in heme synthesis; negative feedback)

Question 4

What would you see in intra-hepatic jaundice?

Answer 4

Impaired hepatic uptake, conjugation, or secretion of conjugated BR
increases in unconjugated and conjugated BR
increased ALT and AST

Question 5

What does heme oxygenase do?

Answer 5

heme –> biliverdin

Question 6

Which porphyria is both hepatic and erythropoietic?

Answer 6

porphyria cutanea tarda (PCT)

Question 7

What part of heme synthesis occurs in the cytosol?

Answer 7

generation of porphyrin ring

Question 8

What is phototherapy used for, and how does it work?

Answer 8

to treat jaundiced newborns

When exposed to blue fluorescent light –> BR converts to form more soluble isomers –> pee it out

Question 9

What does biliverdin reductase do?

Answer 9

biliverdin –> bilirubin

Question 10

What is Crigler-Najjar Syndrome?

Answer 10

deficiency of UDP-GT
type 1 = complete absence = severe hyperBR
Type 2 = mutation in gene, enzyme has 10% activity = benign

Question 11

What is the ferric state of oxygen?

Answer 11

Fe3+

Question 12

What is Porphyria Cutanea Tarda (PCT)?

Answer 12

Defect in UPG decarboxylase (UPG III –> CoPG III)
both liver and blood
most common porphyria in US; skin bubbles, red urine
upg gets oxidized

Question 13

What would you see in pre-hepatic jaundice?

Answer 13

increased levels of unconjugated/indirect BR

normal ALT and AST

Question 14

What is congenital erythropoietic porphyria due to?

Answer 14

defect in Uroporphrinogen III synthase (HMB –> UPG III)
erythropoietic = photosensitivity; red urine and teeth; anemia
accumulation of UPG I and its oxidation product Uroporphyrin I

Question 15

What is the order of products in heme synthesis?

Answer 15

Gly + succyl coA –> ALA (2) –> PPG –> Hydroxymethylbilane –> UPG III –> co PG III –> protoPG 9 –> protophorphyrin 9 –> Heme

Question 16

What is acute intermittent porphyria due to?

Answer 16

Defect in PBG deaminase (PBG–>hydroxymethylbilane)
hepatic = neuro symptoms
excess of ALA and PBG

Question 17

Vitamin B6 is needed for what enzyme in Heme synthesis?

Answer 17

ALA synthase

Question 18

What is variegate porphyria?

Answer 18

Defect in protoporphrinogen IX oxidase (PPG –> protoporphyrin IX)
hepatic = neuro and photosensitivity
historic figures have had this

Question 19

Which porphyria is erythropoietic?

Answer 19

congenital erythropoietic porphyria

Question 20

What part of heme synthesis occurs in the mitochondria?

Answer 20

phase 1: generation of ALA

phase 3: generation of protoporphyrin and intro of iron

Question 21

What form of iron is found in heme?

Answer 21

Fe2+ = ferrous state

Question 22

What is the only one of the porphyrias we learned that isn’t audosomal dominant?

Answer 22

Congenital erythropoietic porphyria

Autosomal recessive

Question 23

What causes neonatal jaundice?

Answer 23

Fetal hb going to hb A = a lot of heme breakdown, and liver can’t keep up
deficiency in UDP-GT enzyme

Question 24

What is heme made of?

Answer 24

four 5-membered rings

iron in ferrous state

Question 25

What is Gilbert Syndrome?

Answer 25

relatively common, benign syndrome

reduced activitey of UDP-GT (25%) –> serum br a little higher than normal

Question 26

What does UDP-glucoronyl transferase do?

Answer 26

adds udp-glucose to bilirubin –> BR-monoglucoronide and then again –> BR-diglucoronide

Question 27

What are the symptoms of Criggler Najjar syndrome type I?

How is treated?

Answer 27

severe high BR –> accumulates in brain –> kernicturus
Therapy: blood transfusions, phototherapy, heme oxygenase inhibitors, oral calcium phosphate and carbonate, liver transplant

Question 28

what would you see in post-hepatic jaundice?

Answer 28

Problems with BR excretion (obstruction to biliary drainage)
elevated conjugated BR in blood and urine
no urobilin in urine
no stercobilin in feces = pale stool

Question 29

What enzymes does lead inactivate?

Answer 29

ALA dehydratase (2ALA-->porphobilinogen)
and ferrochelatase (protoporphyrin -->heme)