Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Difluoromethylornithine (DFMO), a non-competitive inhibitor of ornithine decarboxylase (ODC), the rate limiting enzyme of the polyamine synthetic pathway was evaluated in a Phase I trial. Intravenous DFMO was given to twenty patients with refractory leukemia by continuous infusion in doses from 5.5 to 64 g/m2. Toxicity clearly attributable to the drug was not severe and other than nausea and vomiting did not increase with dose. The previously reported ototoxicity which occurred with the oral form appeared to be less frequent. Loss of hearing which improved when the drug was stopped was seen in four patients, three of whom were simultaneously receiving aminoglycosides. Anorexia occurred in some patients at all doses. Vomiting, necessitating dosage reduction, was a significant problem at the highest dose administered. No patient achieved a remission but there was stabilization or decrease in circulating blast cells in several patients. This growth inhibition did not appear to be dosage related.
 ...
PMID:Phase I evaluation of intravenous difluoromethylornithine--a polyamine inhibitor. 393 6

The aim of this study was to investigate whether the central nervous system regulates mucosal cell growth and apoptosis in the rat small intestine. Ornithine decarboxylase is a key enzyme for polyamine synthesis, which plays an important role in intestinal mucosal growth. The increase in ornithine decarboxylase activity in the duodenum just before a dark period was abolished by truncal vagotomy. An infusion of 2-deoxy-D-glucose into the third cerebroventricle activated the enzyme activity in the small intestine. Epithelial homeostasis is balanced by the regulation of cell proliferation and cell death. Intestinal mucosal apoptosis decreased in rats with ventromedial hypothalamus lesions, which induced hyperphagia and obesity. In contrast, sustained anorexia induced by 1-deoxy-D-glucosamine increased intestinal apoptosis. These results indicate that the central nervous system, in addition to local factors, is related to the regulation of mucosal homeostasis in the intestinal mucosa.
 ...
PMID:Homeostasis in the small intestinal mucosa balanced between cell proliferation and apoptosis is regulated partly by the central nervous system. 1257 82