Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.6.1.2 (
guanylate cyclase
)
8,497
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Holocarboxylase synthetase
(
HCS
) catalyzes the covalent attachment of biotin to five biotin-dependent carboxylases in human cells. Multiple carboxylase deficiency (MCD) is a life-threatening disease characterized by the lack of carboxylase activities because of deficiency of
HCS
activity. Here, we report the obligatory participation of
HCS
in the biotin-dependent stimulation of the level of
HCS
mRNA and those of acetyl-CoA carboxylase and the alpha subunit of propionyl-CoA carboxylase in human cells. Fibroblasts from patients with MCD are unable to increase
HCS
mRNA in response to biotin unless the vitamin concentration is raised 100-fold, in keeping with mutations that cause a reduced affinity for biotin by the mutant enzyme. The outcome is deficient synthesis of biotinyl-5'-AMP, the active form of the vitamin in the biotinylation reaction.
HCS
and carboxylase mRNA levels in normal and MCD fibroblasts and HepG2 cells can be restored by the addition of the cGMP analogue, 8-Br-cGMP, and can be abolished by the addition of inhibitors of the soluble form of
guanylate cyclase
. We propose a regulatory role for biotin in the control of
HCS
and carboxylase mRNA levels through a signaling cascade that requires
HCS
,
guanylate cyclase
, and cGMP-dependent protein kinase.
...
PMID:Holocarboxylase synthetase is an obligate participant in biotin-mediated regulation of its own expression and of biotin-dependent carboxylases mRNA levels in human cells. 1195 85
