Heme Synthesis and Breakdown

Question 1

porphyrin rings:

Answer 1

– Have Four 5-membered rings containing nitrogen connected by
single carbon bridges
– Iron present in ferrous state
– Oxidation to ferric states inactivates hemoglobin
(methemoglobin)

Question 2

where does biosynthesis of heme occur?

Answer 2

in liver and erythroid cells of bone marrow

Question 3

phase 1 of heme synthesis

Answer 3

• in Mito

- Gly and Succinyl Coa to ALA

Question 4

what coenzyme does ALA synthase require?

Answer 4

B6 (pyridoxal phosphate)

Question 5

what enzyme does Phase 1 of heme synthesis require?

Answer 5

ALA synthase

Question 6

build up of heme causes feedback inhibition of what?

Answer 6

ALA synthase

Question 7

what does lead inactivate in heme synthesis

Answer 7

ALA dehydratase and ferrochelatase

Question 8

what does lead poisoning cause

Answer 8

build up of ALA and protoporphyrin IX

• ALA= neurotoxic
• causes anemia
• impacts energy production (cytochromes not synthesized)

Question 9

Porphyrias

Answer 9

inherited metabolic disorders

-defects in heme synthesis

Question 10

what are two types of porphyrias

Answer 10

Acute Hepatic – neurological symptoms

Erythropoietic – skin, photosensitivity

Question 11

Acute intermittent porphyria

Answer 11

defective PBG deaminase (in liver)

-hepatic

Question 12

Congenital erythropoietic porphyria

Answer 12

Uroporphyrinogen III synthase (in erythrocytes)
-build up of
uroporphyrinogen I and its
oxidation product uroporphyrin I
Produce a red color in urine, red
fluorescence in teeth, destruction of
rbc, and skin photosensitivity
-type: erythropoietic

Question 13

Porphyria cutanea tarda (PCT)

Answer 13

uroporphyrinogen decarboxylase

• type: hepatoerythropoietic
• most common in US

Question 14

variegate prophyria (celebrity)

Answer 14

Protoporphyrinogen IX oxidase
-type: hepatic
(King George III)

Question 15

what system degrades hemoglobin

Answer 15

reticulo-endothelial

system

Question 16

what is globin broken down to?

Answer 16

amino acids

Question 17

jaundice (hyperbilirubinemia)

Answer 17

• elevated levels of BR in blood stream

- imbalance between production and excretion of bilirubin

Question 18

Pre-hepatic jaundice

Answer 18

Increased production of unconjugated BR

-elevated blood levels of unconjugated or indirect BR

Question 19

Intra-hepatic jaundice

Answer 19

Impaired hepatic uptake, conjugation, or
secretion of conjugated BR
-Criggler-Najjar syndrome
-Gilbert syndrome
• Increase in serum ALT and AST
• Urobilinogen levels in urine normal
• Conjugated BR detected in urine

Question 20

post hepatic jaundice (AKA Cholestatic jaundice or cholestasis (decreased bile
flow)

Answer 20

• Problems with BR excretion
• Elevated blood levels of conjugated BR
• Conjugated BR is present in urine (dark).
-pale stool

Question 21

Neonatal Jaundice (physiological jaundice)

Answer 21

Immature hepatic metabolic pathways, unable to conjugate and
excrete bilirubin.
• Deficiency of UDP-GT enzyme
• Breakdown of fetal hemoglobin as it is replaced with adult
hemoglobin (unable to keep up with bilirubin excretion)

Question 22

what is used to treat jaundiced newborns?

Answer 22

Phototherapy
When exposed to blue fluorescent light, BR undergoes
photoconversion to form a more soluble isomers.
or
intramuscular injection of tin-
mesoporphyrin (strong inhibitor of heme oxygenase)

Question 23

Crigler-Najjar Syndrome type 1

Answer 23

-complete absence of gene for UDP-GT
-Severe hyperbilirubinemia
-BR accumulates in brain of babies
• Causes encephalopathy (kernicturus) and brain damage

Question 24

Criggler-Najjar Syndrome Type II

Answer 24

-benign form
-mutation in the UDP-GT gene
• Enzyme has less activity (10% activity)

Question 25

Gilbert Syndrome

Answer 25

• Relatively common, benign disorder affecting 2-10% of
population
• Results from reduced activity of UDP-GT (25%
activity)
-slightly increased serum bR

Question 26

Hepatitis

Answer 26

Inflammation of the liver
• Leads to liver dysfunction
• Causes – viral infections (Hep A, B, C), alcoholic
cirrhosis, liver cancer.
• Increased levels of unconjugated and
conjugated BR in blood
• BR accumulates in skin and sclera of the eyes,
causing yellow discoloration
• Dark, tea colored urine