BMB 401 Exam #2 – Study Guide, Practice Questions & Revision Notes
membranes of the mitochondria - ANS ✔✔outer and inner membrane
inner mitochondrial membrane - ANS ✔✔just inside the matrix- the site of many biosynthetic
and catabolic reactions (including some of the reactions in heme synthesis)
heme synthesis - ANS ✔✔-begins and ends in the mitochondrial matrix
-synthesis of the ring involves mitochondrial and cytosolic enzymes
first step in heme synthesis - ANS ✔✔formation of protoporphyrin IX
reaction involved in the formation of protoporphyrin IX - ANS ✔✔condensation reaction
between succinyl CoA (product of the TCA cycle) and glycine (amino acid) to form delta-
aminolevulinate
*this is the first step AND rate limiting step so it is highly regulated
byproducts of the formation of protoporphyrin IX - ANS ✔✔Co2 and coenzyme A
enzyme used in formation of protoporphyrin IX - ANS ✔✔delta-aminolevulinate synthase (ALAS)
where does the formation of protoporphyrin IX occur - ANS ✔✔in the mitochondrial matrix
regulation of heme synthesis - ANS ✔✔high concentrations of heme regulate the
concentrations of delta-ALAS through a negative feedback mechanism
-high heme concentration down regulates...
+transcription of delta-ALAS mRNA
,+translation of mRNA to make the enzyme
+can prevent the translocation of this protein (delta-ALAS) from the cytosol where it is
translated into the mitochondrial matrix where it works
second step in heme synthesis - ANS ✔✔porphobilinogen synthesis
how is the rate limiting step of heme synthesis regulated - ANS ✔✔through negative feedback
by the heme itself (inhibit translation, transcription, and transport)
porphobilinogen synthesis reaction - ANS ✔✔delta-ALA transported to the cytosol
2 required for every 1 mc of porphobilinogen
enzyme involved in porphobilinogen synthesis - ANS ✔✔porphobilinogen synthase
reactants and products of porphobilinogen synthesis - ANS ✔✔8 molecules of delta-ALA --> 4
porphobilinogen
third step in heme synthesis - ANS ✔✔deamination/polymerization of 4 pyrrole units
reactants and products of deamination - ANS ✔✔R: 4 molecules of porphobilinogen (4
necessary for heme synthesis)
P: a linear tetrapyrrole (pre-uroporphyrinogen) and 4 NH4+ molecules
enzyme used in deamination - ANS ✔✔porphobilinogen deaminase
step 4 of heme synthesis - ANS ✔✔cyclization
,enzymes involved in cyclization - ANS ✔✔uroporphyrinogen III synthase
(catalyzes the cyclization of the linear tetrapyrolle to form an asymmetric ring)
product of cyclization - ANS ✔✔uroporphyrinogen III
-hanging off the rings are an acetate and propionate moiety
-during cyclization one of the rings flips and leaves an acetate next to itself and a propionate
next to itself
step 5 of heme synthesis - ANS ✔✔reoranization
where does reorganization occur - ANS ✔✔in the mitochondria
reorganization reactions - ANS ✔✔forms methyl and vinyl side chains and alters the saturation
of ring constituents so that we end with a protoporphyrin IX
step 6 of heme synthesis - ANS ✔✔chelation
enzyme involved with chelation - ANS ✔✔ferrochelatase - chelates ferrous iron (Fe2) into
protoporphyrin IX to form heme
porphyrias - ANS ✔✔problems with the heme synthetic pathway
1) acute intermittent
2) congenital erythropoietic
each caused by a deficiency in a particular enzyme
cause of acute intermittent porphyria - ANS ✔✔aka porphobilinogen deaminase deficiency
(step 3)
, if concentration or activity level of enzyme is insufficient there is a decrease in the formation of
the linear tetrapyrrole and a buildup of everything that comes before it (delta-ALA and
porphobilinogen)
symptoms of acute intermittent porphyria - ANS ✔✔severe abdominal pain, neurological
dysfunction
cause of congenital erythropoietic porphyria - ANS ✔✔deficiency in uroporphyrinogen III
synthase (step 4)
causes formation of a symmetric ring (conjugated system that absorbs light easily,
uroporphyrinogen I) = dead end = builds up under the skin and in the teeth
symptoms of congenital erythropoietic porphyria - ANS ✔✔skin becomes hypersensitive to sun,
fluorescent red teeth
3 parts to hemoglobin catabolism - ANS ✔✔1) breaking down globin chains
2) breaking down the heme ring
3) recycling the iron
major site of hemoglobin catabolism - ANS ✔✔the spleen
spleen - ANS ✔✔organ located in the upper left abdomen; filters aging red blood cells from the
bloodstream; site where the majority of hemoglobin is broken down
step 1 of hemoglobin catabolism - ANS ✔✔ring itself is broken down into more linear form
(biliverdin), iron is released
products: CO, H2O, NADP+
membranes of the mitochondria - ANS ✔✔outer and inner membrane
inner mitochondrial membrane - ANS ✔✔just inside the matrix- the site of many biosynthetic
and catabolic reactions (including some of the reactions in heme synthesis)
heme synthesis - ANS ✔✔-begins and ends in the mitochondrial matrix
-synthesis of the ring involves mitochondrial and cytosolic enzymes
first step in heme synthesis - ANS ✔✔formation of protoporphyrin IX
reaction involved in the formation of protoporphyrin IX - ANS ✔✔condensation reaction
between succinyl CoA (product of the TCA cycle) and glycine (amino acid) to form delta-
aminolevulinate
*this is the first step AND rate limiting step so it is highly regulated
byproducts of the formation of protoporphyrin IX - ANS ✔✔Co2 and coenzyme A
enzyme used in formation of protoporphyrin IX - ANS ✔✔delta-aminolevulinate synthase (ALAS)
where does the formation of protoporphyrin IX occur - ANS ✔✔in the mitochondrial matrix
regulation of heme synthesis - ANS ✔✔high concentrations of heme regulate the
concentrations of delta-ALAS through a negative feedback mechanism
-high heme concentration down regulates...
+transcription of delta-ALAS mRNA
,+translation of mRNA to make the enzyme
+can prevent the translocation of this protein (delta-ALAS) from the cytosol where it is
translated into the mitochondrial matrix where it works
second step in heme synthesis - ANS ✔✔porphobilinogen synthesis
how is the rate limiting step of heme synthesis regulated - ANS ✔✔through negative feedback
by the heme itself (inhibit translation, transcription, and transport)
porphobilinogen synthesis reaction - ANS ✔✔delta-ALA transported to the cytosol
2 required for every 1 mc of porphobilinogen
enzyme involved in porphobilinogen synthesis - ANS ✔✔porphobilinogen synthase
reactants and products of porphobilinogen synthesis - ANS ✔✔8 molecules of delta-ALA --> 4
porphobilinogen
third step in heme synthesis - ANS ✔✔deamination/polymerization of 4 pyrrole units
reactants and products of deamination - ANS ✔✔R: 4 molecules of porphobilinogen (4
necessary for heme synthesis)
P: a linear tetrapyrrole (pre-uroporphyrinogen) and 4 NH4+ molecules
enzyme used in deamination - ANS ✔✔porphobilinogen deaminase
step 4 of heme synthesis - ANS ✔✔cyclization
,enzymes involved in cyclization - ANS ✔✔uroporphyrinogen III synthase
(catalyzes the cyclization of the linear tetrapyrolle to form an asymmetric ring)
product of cyclization - ANS ✔✔uroporphyrinogen III
-hanging off the rings are an acetate and propionate moiety
-during cyclization one of the rings flips and leaves an acetate next to itself and a propionate
next to itself
step 5 of heme synthesis - ANS ✔✔reoranization
where does reorganization occur - ANS ✔✔in the mitochondria
reorganization reactions - ANS ✔✔forms methyl and vinyl side chains and alters the saturation
of ring constituents so that we end with a protoporphyrin IX
step 6 of heme synthesis - ANS ✔✔chelation
enzyme involved with chelation - ANS ✔✔ferrochelatase - chelates ferrous iron (Fe2) into
protoporphyrin IX to form heme
porphyrias - ANS ✔✔problems with the heme synthetic pathway
1) acute intermittent
2) congenital erythropoietic
each caused by a deficiency in a particular enzyme
cause of acute intermittent porphyria - ANS ✔✔aka porphobilinogen deaminase deficiency
(step 3)
, if concentration or activity level of enzyme is insufficient there is a decrease in the formation of
the linear tetrapyrrole and a buildup of everything that comes before it (delta-ALA and
porphobilinogen)
symptoms of acute intermittent porphyria - ANS ✔✔severe abdominal pain, neurological
dysfunction
cause of congenital erythropoietic porphyria - ANS ✔✔deficiency in uroporphyrinogen III
synthase (step 4)
causes formation of a symmetric ring (conjugated system that absorbs light easily,
uroporphyrinogen I) = dead end = builds up under the skin and in the teeth
symptoms of congenital erythropoietic porphyria - ANS ✔✔skin becomes hypersensitive to sun,
fluorescent red teeth
3 parts to hemoglobin catabolism - ANS ✔✔1) breaking down globin chains
2) breaking down the heme ring
3) recycling the iron
major site of hemoglobin catabolism - ANS ✔✔the spleen
spleen - ANS ✔✔organ located in the upper left abdomen; filters aging red blood cells from the
bloodstream; site where the majority of hemoglobin is broken down
step 1 of hemoglobin catabolism - ANS ✔✔ring itself is broken down into more linear form
(biliverdin), iron is released
products: CO, H2O, NADP+
