heme metabolism Flashcards
heme structure
porphyrin ring + iron + protoporphyrin 9
what is heme
an iron-containing cofactor for hemoglobin
what is the committed step of heme synthesis
glycine + succinyl-CoA
–(ALAS)–>
ALA
->
->
->
heme
what catalyzes the committed step of heme synthesis, & how does this differ by location
ALAS1 in liver
ALAS2 in bone marrow
heme synthesis pathway
what is HIF
Hypoxia-Inducible (transcription) Factor
HIF in normoxia pathway
HIF-OH
->
ubiquinated by VHL1
->
degradation by protease
HIF in hypoxia pathway
HIF increases transcription of gene Epo
->
Epo binds EpoR in bone marrow
->
increases RBC production
Epo is a _____ that controls _____
cytokine
erythropoiesis
what is the Bohr effect
^ [H+], CO2 = ^ O2 release from hemoglobin
what is the “T state” of hemoglobin
low O2 affinity
what does 2,3BPG binding to hemoglobin do
^ O2 release from hemoglobin
high altitude hyperventilation (altitude sickness) causes
respiratory alkalosis
treatment for altitude sickness
carbonic anhydrase inhibitor (blocks CO2 formation)
treatment for CO poisoning, & why
administer high O2
to outcompete CO that was taking O2 binding site on hemoglobin
porphyria
-inheritance
-caused by
-hallmark
autosomal dominant
mutation in heme biosynthesis
purple urine
_____ limits rate of heme formation in erythroid cells
iron
4 types of hemoglobinopathies
alpha thalassemias (anemia)
beta thalassemias (anemia)
sickle cell anemia
HbC disease
sickle cell disease
-inheritance
-caused by
homozygous recessive
mutation in HBB gene
heme catabolism pathway in macrophage
heme catabolism pathway in liver
_____ can result in jaundice
hyperbilirubinemia
3 common types of jaundice
hemolytic
hepatocellular
obstructive/cholestatic
Gilbert’s syndrome
-what is it
-genetic cause
isolated hyperbilirubinemia (unconjugated)
mutations of UGT1A1 gene
