Porphyrin Metabolism Flashcards
The overall synthesis of heme requires what?
8 enzymes, pyridoxal phosphate, Mg2+, O2, and reducing substances
What are the byproducts of heme synthesis?
8 CoA, 14 CO2, 4 NH4
Where is heme synthesis located?
liver and erythropoietic tissue
Erythropoietic tissue forms heme for ____. Liver forms heme for incorporation into ____.
hemoglobin; cytochromes
The first step and the last three steps of heme synthesis are located where?
mitochondria; the rest are cytosolic
This is a mitochondrial enzyme coded for by nuclear genes, synthesized on cytosolic ribosomes, and transported into the mitochondria. It requires pyridoxal phosphate and Mg2+.
Delta-Aminolevulinic acid synthetase
This is a cytosolic enzyme. It allows two molecules of Aminolevulinic Acid (ALA) - formed by D-ALA syntehetase -to condense and form porphobilinogen. It is very sensitive to heavy metals (Pb).
Delta-Aminolevulinate dehydratase
This enzyme and coenzyme allow four molecules of porphobilinogen to condense head-to-tail, and become cyclized to form uroporphyrinogen.
Uroporphyrinogen I synthase I and Uroporphyrinogen III co-synthase (cytosolic)
In the absence of uroporphyrinogen III co-synthase, what occurs, in regards to production of uroporphyrinogen.
In the absence of Uroporphyrinogen III co-synthase, large amounts of uroporphyrinogen I are formed, while in the presence of Uroporphyrinogen III co-synthase, essentially only isomer III is produced.
Urophyrinogen decarboxylase (cytosolic) catalyzes the sequential decarboxylation of the four acetic acid side chains to methyl groups. What is this enzyme inhibited by?
iron salts
What is the role of corproporphyrinogen oxidase, what does it require, and where is it located?
converts the propionic acid groups of ring A and B to vinyl groups. It is specific for the type III isomer.
It requires O2 but no other cofactor or metal
It is located in the mitochondria
This enzyme is specific for protoporphyrinogen IX, requires O2, and reducing substances. The product, protoporphyrin IX is more water insoluble than previous precursors.
protoporphyringoen oxidase (mitochondrial)
This is the last enzyme found in heme synthesis. It inserts ferrous iron into protoporphyrin IX to yield heme. It is sensitive to heavy metals and is membrane associated.
Ferrochelatase (mitochondria)
What is the rate limiting step of heme synthesis in the liver?
D-ALA synthetase
Heme inhibits ALA synthetase at three points. What are they?
inhibition of the synthesis of the enzyme
inhibition of transport of the enzyme into the mitochondria
allosteric inhibitor of the enzyme activity
