Heme is the prosthetic group for ______
hemoglobin, myoglobin, the cytochromes, catalase, tryptophan pyrrolase
Only _____ porphyrins,which contain an asymmetric substitution on_____ (see Figure21.2), are physiologically important in humans.
Type III , ring D
Most important Nitrogen containing compounds synthesized from amino acids
porphyrins, neurotransmitters, hormones, melanin, creatine
neurotransmitters synthesized from amino acids
catecholamines, serotonin, melatonin
Hormones synthesized from amino acids
thyroid hormones are synthesized from tyrosine
melanin is synthesized from
Porphyrins are made of _____ rings
The color in porphyrins comes from
conjugated double bonds
T or F:
Porphyrinogens and porphyrins are colored compounds
False, porphyrinogens the precursors to porphyrins, are colorless
Protoporphyrin IX is found in
protoporphyrin IX, has ____ side chains on the tetrapyrrole ring
4 Methyl, 2 vinyl, 2 propionic
First step in heme biosynthesis
condensation of glycine and succinyl CoA to form δ-aminolevulinate
first step of heme biosynthesis is catalyzed by
Coenzyme of ALA synthase
ALA synthase is present in
What is the rate limiting reaction of heme biosynthesis?
condensation of glycine and succinyl CoA to form δaminolevulinate catalyzed by ALA synthase
_____ dimerizes 2 molecules of ALA to produce the pyrrole ring compound porphobilinogen
Control point of heme biosynthesis
_____catalyzes the head to tail condensation of 4 molecules of porphobilinogen to produce the linear tetrapyrrole intermediate, hydroxymethylbilane
porphobilinogen deaminase (PGB deaminase, uroporphyrinogen I synthase)
uroporphyrinogen III synthase does what?
catalyzes conversion of hydroxymethylbilane to urophorphyrinogen III
______ decarboxylates the acetate substituents of uroporphyrinogen in the cytosol
acetate substituents of uroporhyrinogen III are converted to _____ substituents in coproporphyrinogen IIII
coproporphyrinogen III is transported to
Coproporphyrinogen oxidase does what?
decarboxylates two propionate residues, yielding vinyl substituents on the 2 of the pyrrole rings in colorless protoporphyrinogen IX
where is protoporphyrinogen IX converted to protoporphyrin IX?
What does protoporphyrinogen IX oxidase do?
converts protoporphyrinogen IX to Protoporphyrin IX
what does protoporphyrinogen IX oxidase require?
What is responsible for the characteristic red color of heme?
completely conjugated ring system
what is the final reaction of heme biosynthesis?
insertion of iron atom into the ring system of protoporphyrin IX, generating heme b
what catalyzes the last reaction of heme biosynthesis?
ferrochelatase and ALA dehydratase are highly sensitive to inhibition by
heavy metal poisoning
Increase in ALA in the circulation in the absence of an increase in porphobilinogen is characteristic of
where does heme biosynthesis take place?
erythroid cells (85%) and hepatocytes
In hepatocytes, the rate limiting step of heme biosynthesis is
In hepatocytes, heme accumulation leads to what?
Fe3+ oxidation product of heme (hemin),
what does hemin do to ALA synthase?
inhibits transport of ALA synthase from the cytosol to the mitochondria and represses synthesis of the enzyme
_____ represses synthesis of ALA synthase
What has a regulatory role in heme biosynthesis in erythroid cells?
Drugs that are accompanied by an induction in the system that cause an increase in the synthesis of heme
griseofulvin, hydantoins, phenobarbital
porphyrias occur due to abnormalities in
the pathway of biosynthesis of heme
All of the porphyrias are inherited _____ except congenital Erythropoietic porphyria which is _____
All of the porphyrias are inherited autosomal dominant except for Congenital Erythropoietic Porphyria which is autosomal recessive
describe porphyrin photosensitivity
Porphyrins absorb light at 400nm excited react with O2 free radicals which damage lysosomes and other organelle skin damage and scarring
Clinical features of porphyria can be precipitated by
drugs that induce the cytochrome P450 system
What does heme oxygenase do?
opens up heme ring n the ER
What does heme oxygenase produce?
linear tetrapyrrole biliverdin, ferric iron (Fe3+), CO
What does biliverdin reductase do?
it reduces a seond bridging methylene between rings III, IV of heme, producing bilirubin
Describe the color change from biliverdin to bilirubin
biliverdin is blue green, bilirubin is yello-red. This is because bilirubin is less conjugated
T or F:
Bilirubin requires albumin to be transferred to the liver
What does UDP glucuronyl transferase do to bilirubin in hepatocytes?
adds 2 glucuronic acid molecules to bilirubin, makes it more water soluble bilirubin diglucuronide, leads to excretion with bile as bile pigments
In the intestine, bilirubin glucuronides are deconjugated by bacterial beta-glucuronidases and degraded to
what happens to urobilinogens in the intestines?
they are oxidized to stercobilin and give the brown color to feces
Bilirubin and its catabolic products are collectively known as the
The initial reaction and the last three steps in the formation of porphyrins occur in the __1___, where as the intermediate steps of the biosynthetic pathway occur in the __2___
1. mitochondria, 2. Cytosol
All carbon and nitrogen atoms of a porphyrin molecule come from _____ and _____
glycine and succinyl CoA
In erythroid cells, heme synthesis is under the control of _____
erythropoietin and the availability of intracellular ion
Individuals with an enzyme defect leading to the accumulation of tetrapyrrole intermediates show _____