Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:2.5.1.61 (
porphobilinogen deaminase
)
637
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Porphobilinogen deaminase (
hydroxymethylbilane synthase
; EC 4.3.1.8), the third enzyme of the heme biosynthetic pathway, catalyzes the stepwise condensation of four porphobilinogen units to yield hydroxymethylbilane, which is in turn converted to uroporphyrinogen III by cosynthetase. We compared the apparent molecular mass of
porphobilinogen deaminase
from erythropoietic and from non-erythropoietic cells by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and immune-blotting. The results indicate that two isoforms of
porphobilinogen deaminase
can be distinguished and differ by 2000 Da. Analysis of cell-free translation products directed by mRNAs from human erythropoietic spleen and from human liver demonstrates that the two isoforms of
porphobilinogen deaminase
are encoded by distinct messenger RNAs. We cloned and sequenced cDNAs complementary to the non-erythropoietic form of
porphobilinogen deaminase
encoding RNA. Comparison of these sequences to that of human erythropoietic mRNA [Raich et al. (1986) Nucleic Acids Res. 14, 5955-5968] revealed that the two mRNA species differ by their 5' extremity. From the mRNA sequences we could deduce that an additional peptide of 17 amino acid residues at the NH2 terminus of the non-erythropoietic isoform of
porphobilinogen deaminase
accounts for its higher molecular mass.
RNase
mapping experiments demonstrate that the two
porphobilinogen deaminase
mRNAs are distributed according to a strict tissue-specificity, the erythropoietic form being restricted to erythropoietic cells. We propose that a single
porphobilinogen deaminase
gene is transcribed from two different promoters, yielding the two forms of
porphobilinogen deaminase
mRNAs. Our present finding may have some relevance for further understanding the
porphobilinogen deaminase
deficiency in certain cases of acute intermittent porphyria with an enzymatic defect restricted in non-erythropoietic cells.
...
PMID:Tissue-specific expression of porphobilinogen deaminase. Two isoenzymes from a single gene. 381 74
