Heme Synthesis and Breakdown Flashcards
Which porphyrias are hepatic?
acute intermittent
variegate
What happens to BR levels in hepatitis?
Increased levels of unconjugated and conjugated BR
What enzyme does Heme inhibit?
ALA synthase (first enzyme in heme synthesis; negative feedback)
What would you see in intra-hepatic jaundice?
Impaired hepatic uptake, conjugation, or secretion of conjugated BR
increases in unconjugated and conjugated BR
increased ALT and AST
What does heme oxygenase do?
heme –> biliverdin
Which porphyria is both hepatic and erythropoietic?
porphyria cutanea tarda (PCT)
What part of heme synthesis occurs in the cytosol?
generation of porphyrin ring
What is phototherapy used for, and how does it work?
to treat jaundiced newborns
When exposed to blue fluorescent light –> BR converts to form more soluble isomers –> pee it out
What does biliverdin reductase do?
biliverdin –> bilirubin
What is Crigler-Najjar Syndrome?
deficiency of UDP-GT
type 1 = complete absence = severe hyperBR
Type 2 = mutation in gene, enzyme has 10% activity = benign
What is the ferric state of oxygen?
Fe3+
What is Porphyria Cutanea Tarda (PCT)?
Defect in UPG decarboxylase (UPG III –> CoPG III)
both liver and blood
most common porphyria in US; skin bubbles, red urine
upg gets oxidized
What would you see in pre-hepatic jaundice?
increased levels of unconjugated/indirect BR
normal ALT and AST
What is congenital erythropoietic porphyria due to?
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
What is the order of products in heme synthesis?
Gly + succyl coA –> ALA (2) –> PPG –> Hydroxymethylbilane –> UPG III –> co PG III –> protoPG 9 –> protophorphyrin 9 –> Heme
What is acute intermittent porphyria due to?
Defect in PBG deaminase (PBG–>hydroxymethylbilane)
hepatic = neuro symptoms
excess of ALA and PBG
Vitamin B6 is needed for what enzyme in Heme synthesis?
ALA synthase
What is variegate porphyria?
Defect in protoporphrinogen IX oxidase (PPG –> protoporphyrin IX)
hepatic = neuro and photosensitivity
historic figures have had this
Which porphyria is erythropoietic?
congenital erythropoietic porphyria
What part of heme synthesis occurs in the mitochondria?
phase 1: generation of ALA
phase 3: generation of protoporphyrin and intro of iron
What form of iron is found in heme?
Fe2+ = ferrous state
What is the only one of the porphyrias we learned that isn’t audosomal dominant?
Congenital erythropoietic porphyria
Autosomal recessive
What causes neonatal jaundice?
Fetal hb going to hb A = a lot of heme breakdown, and liver can’t keep up
deficiency in UDP-GT enzyme
What is heme made of?
four 5-membered rings
iron in ferrous state
What is Gilbert Syndrome?
relatively common, benign syndrome
reduced activitey of UDP-GT (25%) –> serum br a little higher than normal
What does UDP-glucoronyl transferase do?
adds udp-glucose to bilirubin –> BR-monoglucoronide and then again –> BR-diglucoronide
What are the symptoms of Criggler Najjar syndrome type I?
How is treated?
severe high BR –> accumulates in brain –> kernicturus
Therapy: blood transfusions, phototherapy, heme oxygenase inhibitors, oral calcium phosphate and carbonate, liver transplant
what would you see in post-hepatic jaundice?
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
What enzymes does lead inactivate?
ALA dehydratase (2ALA-->porphobilinogen) and ferrochelatase (protoporphyrin -->heme)
