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
T or F:
Porphyrinogens and porphyrins are colored compounds
False, porphyrinogens the precursors to porphyrins, are colorless
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
_____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 oxidase does what?
decarboxylates two propionate residues, yielding vinyl substituents on the 2 of the pyrrole rings in colorless protoporphyrinogen IX
what is the final reaction of heme biosynthesis?
insertion of iron atom into the ring system of protoporphyrin IX, generating heme b
Increase in ALA in the circulation in the absence of an increase in porphobilinogen is characteristic of
what does hemin do to ALA synthase?
inhibits transport of ALA synthase from the cytosol to the mitochondria and represses synthesis of the enzyme
Drugs that are accompanied by an induction in the system that cause an increase in the synthesis of heme
griseofulvin, hydantoins, phenobarbital
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
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
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
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