Linked Life Data

16302824

Source:http://linkedlifedata.com/resource/pubmed/id/16302824

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2005-11-23
pubmed:abstractText
A lately discovered carbonic anhydrase (hCA, EC 4.2.1.1), the mitochondrial hCA VB, was cloned, expressed, and purified. Kinetic parameters proved it to be 3.37 times more effective than hCA VA as a catalyst for the physiological reaction, with kcat = 9.5 x 10(5) s(-1) and kcat/K(M) = 9.8 x 10(7) M(-1) s(-1), being second only to hCA II among the 16 isoforms presently known in humans. We investigated the inhibition of hCA VB with a library of sulfonamides/sulfamates, some of which are clinically used compounds. Benzenesulfonamides were ineffective inhibitors, whereas derivatives bearing 4-amino, 4-hydrazino, 4-methyl, 4-carboxy moieties or halogenated sulfanilamides were more effective (Ki's of 1.56-4.3 microM). Among the 10 clinically used compounds, acetazolamide, benzolamide, topiramate, and indisulam showed effective inhibitory activity (Ki's of 18-62 nM). Three compounds showed better activity against hCA VB over hCA II, among which were sulpiride and ethoxzolamide, which were 2 times more effective inhibitors of the mitochondrial over the cytosolic isozyme. hCA VB is a druggable target and some of its inhibitors may lead to the development of novel antiobesity therapies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7860-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Carbonic anhydrase inhibitors. The mitochondrial isozyme VB as a new target for sulfonamide and sulfamate inhibitors.
pubmed:affiliation
Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
pubmed:publicationType
Journal Article, Comparative Study