Molecular analysis of a human liver mitochondrial ornithine transcarbamylase deficiency.
The liver of a young girl which had been successfully transplanted was investigated at the ornithine transcarbamylase (OTC, EC 2.1.3.3) gene expression level. Northern blot hybridization using a human OTC cDNA probe showed a greater than 80% decrease in specific OTC mRNA although having the same molecular size as a normal control. OTC polypeptide was simultaneously synthesized with a normal molecular size but at a low level (20%) as shown by immunoblotting. The OTC enzyme from the deficient liver exhibited very little catalytic activity (7.2% as compared to the normal subject). These results may support several explanations of this disease such as mutation of the OTC gene promoter leading to a low transcriptional activity or mutation of the encoding sequence which results in a modified translation product but with a normal size. mRNA instability may also occur.
Berrez
J M
JM
Laboratoire de Biochimie et Biologie Moléculaire (UA CNRS 531), Université de Franche-Comté, Bescançon, France.
Bardot
O
O
Thiard
M C
MC
Alvarez
F
F
Latruffe
N
N
D015152:Blotting, Northern; D002384:Catalysis; D002675:Child, Preschool; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D005260:Female; D006801:Humans; D008930:Mitochondria, Liver / Q000201:enzymology*; D009693:Nucleic Acid Hybridization; D009954:Ornithine Carbamoyltransferase / Q000032:analysis / Q000378:metabolism; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D010455:Peptides / Q000032:analysis / Q000737:chemistry; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism
D010455:Peptides; D012333:RNA, Messenger; D012313:RNA; D004247:DNA; D009954:Ornithine Carbamoyltransferase