HEME METABOLISM AND HB BIOCHEMISTRY
EXAM QUESTIONS AND ANSWERS
How is glycolysis related to heme metabolism?
The NADH generated from glycolysis can be used to reduce
methemoglobin (Fe3+) to normal hemoglobin (Fe2+), or to convert
pyruvate to lactate so that NAD+ can be regenerated and used for
glycolysis.
2,3-BPG is also generated for for oxygen-Hb dissociation
What is the rate-limiting step in heme synthesis?
What enzyme and associated co-factor does this?
What inhibits this rxn?
the conversion of succinyl-CoA and glycine to delta-ALA by delta-ALA
synthase
delta-ALAS needs Vitamin B6 (also known as pyridoxal phosphate)
heme inhibits this
What are the two kinds of ALAS and how are they different?
ALAS1 is needed for heme synthesis in the liver
ALAS2 is needed for in the bone
,What are 3 functions of heme?
- transport and storage of oxygen (hb and mb)
- electron txp
- redox rxns
Why is some heme made in the liver?
heme is an important precursor for cytochrome p450, which is needed
for alcohol and drug detox
What are porphyrias?
diseases associated when any step of the heme synthesis pathway is
messed up
What is the final step in heme synthesis?
formation of heme from protoporphyrin IX via ferrochelatase and Fe2+
Which steps in the heme synthesis occur in the mitochondria and in the
cytosol?
mito: 1, 6, 7, 8
cyto: 2, 3, 4, 5
What is a key characteristic of X-linked sideroblastic anemia?
What enzyme defect causes this, and how would you fix this?
Prussian-blue-stained mitochondria around nucleus due to accumulation
of heme
due to a defect in delta-ALA synthases.
Treatment: Vitamin B6 (pyridoxal phosphate)
The 2nd step of heme synthesis, which is the conversion of delta-ALA to
porphobilinogen, is catalyzed by what enzyme?
What inhibits this reaction?
Where does it happen?
delta-ALA dehydratase (also known as porphobilinogen synthetase)
,inhibited by lead 2+
occurs in cytosol
What is the 3rd step in heme biosynthesis?
What disease is associated when the enzyme is broken?
Where does the reaction occur?
the conversion of porphobilinogen to hydroxymethylbilane by the
enzyme porphobilinogen deaminanse.
this happens in cytosol
If the enzyme does not work, you'll get acute intermittient porphyria
What is the key sign of acute intermittent porphyria?
port vine colored urine
What is the 4th step in heme biosynthesis?
What disease is associated when the enzyme is broken?
Where does the reaction occur?
conversion of hydroxymethylbilane to uroporphobilinogen III by the
enzyme uroporphobiilogen III cosynthase
this happens in cytosol
associated dz is congenital erythropoietic porphryia (due to
accumulation of uroporphobilinogen I (NOT
HYDROXYMETHALBILANE!))
, What is the 5th step in heme biosynthesis?
What disease is associated when the enzyme is broken?
Where does the reaction occur?
conversion of uroporphobilinogen III to coproporphobilinogen III by the
enzyme uroporphobilinogen III decarboxylase
this happens in the cytosol
associated dz is porphyria cutanea tarda
What is a key sign/sx associated with porphyria cutanea tarda?
tea-colored urine, due to accumulation of uroporphyrin
also causes blistering cutaneosus photosensitivity (UV sensitivity)
What is the 6th step in heme biosynthesis?
Where does the reaction occur?
the conversion of coproporphobilinogen III to protoporphobilinogen IX by
the enzyme coproporphobilinogen oxidase
this occurs in the mitochondria
What is the 7th step in heme biosynthesis?
Where does the reaction occur?
EXAM QUESTIONS AND ANSWERS
How is glycolysis related to heme metabolism?
The NADH generated from glycolysis can be used to reduce
methemoglobin (Fe3+) to normal hemoglobin (Fe2+), or to convert
pyruvate to lactate so that NAD+ can be regenerated and used for
glycolysis.
2,3-BPG is also generated for for oxygen-Hb dissociation
What is the rate-limiting step in heme synthesis?
What enzyme and associated co-factor does this?
What inhibits this rxn?
the conversion of succinyl-CoA and glycine to delta-ALA by delta-ALA
synthase
delta-ALAS needs Vitamin B6 (also known as pyridoxal phosphate)
heme inhibits this
What are the two kinds of ALAS and how are they different?
ALAS1 is needed for heme synthesis in the liver
ALAS2 is needed for in the bone
,What are 3 functions of heme?
- transport and storage of oxygen (hb and mb)
- electron txp
- redox rxns
Why is some heme made in the liver?
heme is an important precursor for cytochrome p450, which is needed
for alcohol and drug detox
What are porphyrias?
diseases associated when any step of the heme synthesis pathway is
messed up
What is the final step in heme synthesis?
formation of heme from protoporphyrin IX via ferrochelatase and Fe2+
Which steps in the heme synthesis occur in the mitochondria and in the
cytosol?
mito: 1, 6, 7, 8
cyto: 2, 3, 4, 5
What is a key characteristic of X-linked sideroblastic anemia?
What enzyme defect causes this, and how would you fix this?
Prussian-blue-stained mitochondria around nucleus due to accumulation
of heme
due to a defect in delta-ALA synthases.
Treatment: Vitamin B6 (pyridoxal phosphate)
The 2nd step of heme synthesis, which is the conversion of delta-ALA to
porphobilinogen, is catalyzed by what enzyme?
What inhibits this reaction?
Where does it happen?
delta-ALA dehydratase (also known as porphobilinogen synthetase)
,inhibited by lead 2+
occurs in cytosol
What is the 3rd step in heme biosynthesis?
What disease is associated when the enzyme is broken?
Where does the reaction occur?
the conversion of porphobilinogen to hydroxymethylbilane by the
enzyme porphobilinogen deaminanse.
this happens in cytosol
If the enzyme does not work, you'll get acute intermittient porphyria
What is the key sign of acute intermittent porphyria?
port vine colored urine
What is the 4th step in heme biosynthesis?
What disease is associated when the enzyme is broken?
Where does the reaction occur?
conversion of hydroxymethylbilane to uroporphobilinogen III by the
enzyme uroporphobiilogen III cosynthase
this happens in cytosol
associated dz is congenital erythropoietic porphryia (due to
accumulation of uroporphobilinogen I (NOT
HYDROXYMETHALBILANE!))
, What is the 5th step in heme biosynthesis?
What disease is associated when the enzyme is broken?
Where does the reaction occur?
conversion of uroporphobilinogen III to coproporphobilinogen III by the
enzyme uroporphobilinogen III decarboxylase
this happens in the cytosol
associated dz is porphyria cutanea tarda
What is a key sign/sx associated with porphyria cutanea tarda?
tea-colored urine, due to accumulation of uroporphyrin
also causes blistering cutaneosus photosensitivity (UV sensitivity)
What is the 6th step in heme biosynthesis?
Where does the reaction occur?
the conversion of coproporphobilinogen III to protoporphobilinogen IX by
the enzyme coproporphobilinogen oxidase
this occurs in the mitochondria
What is the 7th step in heme biosynthesis?
Where does the reaction occur?
