Linked Life Data

8547174

Source:http://linkedlifedata.com/resource/pubmed/id/8547174

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5-6
pubmed:dateCreated
1996-2-20
pubmed:abstractText
The isoenzymes of the 3 beta-hydroxysteroid dehydrogenase/5-ene-4-ene-isomerase (3 beta-HSD) gene family catalyse the transformation of all 5-ene-3 beta-hydroxysteroids into the corresponding 4-ene-3-keto-steroids and are responsible for the interconversion of 3 beta-hydroxy- and 3-keto-5 alpha-androstane steroids. The two human 3 beta-HSD genes and the three related pseudogenes are located on the chromosome 1p13.1 region, close to the centromeric marker D1Z5. The 3 beta-HSD isoenzymes prefer NAD+ to NADP+ as cofactor with the exception of the rat liver type III and mouse kidney type IV, which both prefer NADPH as cofactor for their specific 3-ketosteroid reductase activity due to the presence of Tyr36 in the rat type III and of Phe36 in mouse type IV enzymes instead of Asp36 found in other 3 beta-HSD isoenzymes. The rat types I and IV, bovine and guinea pig 3 beta-HSD proteins possess an intrinsic 17 beta-HSD activity specific to 5 alpha-androstane 17 beta-ol steroids, thus suggesting that such "secondary" activity is specifically responsible for controlling the bioavailability of the active androgen DHT. To elucidate the molecular basis of classical form of 3 beta-HSD deficiency, the structures of the types I and II 3 beta-HSD genes in 12 male pseudohermaphrodite 3 beta-HSD deficient patients as well as in four female patients were analyzed. The 14 different point mutations characterized were all detected in the type II 3 beta-HSD gene, which is the gene predominantly expressed in the adrenals and gonads, while no mutation was detected in the type I 3 beta-HSD gene predominantly expressed in the placenta and peripheral tissues. The mutant type II 3 beta-HSD enzymes carrying mutations detected in patients affected by the salt-losing form exhibit no detectable activity in intact transfected cells, at the exception of L108W and P186L proteins, which have some residual activity (approximately 1%). Mutations found in nonsalt-loser patients have some residual activity ranging from approximately 1 to approximately 10% compared to the wild-type enzyme. Characterization of mutant proteins provides unique information on the structure-function relationships of the 3 beta-HSD superfamily.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0960-0760
pubmed:author
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
489-505
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8547174-3-Hydroxysteroid Dehydrogenases, pubmed-meshheading:8547174-Amino Acid Sequence, pubmed-meshheading:8547174-Animals, pubmed-meshheading:8547174-Cattle, pubmed-meshheading:8547174-Chromosome Mapping, pubmed-meshheading:8547174-Endocrine System Diseases, pubmed-meshheading:8547174-Female, pubmed-meshheading:8547174-Genes, pubmed-meshheading:8547174-Humans, pubmed-meshheading:8547174-Isoenzymes, pubmed-meshheading:8547174-Kinetics, pubmed-meshheading:8547174-Male, pubmed-meshheading:8547174-Mice, pubmed-meshheading:8547174-Molecular Sequence Data, pubmed-meshheading:8547174-Multienzyme Complexes, pubmed-meshheading:8547174-Point Mutation, pubmed-meshheading:8547174-Progesterone Reductase, pubmed-meshheading:8547174-Rats, pubmed-meshheading:8547174-Sequence Alignment, pubmed-meshheading:8547174-Sequence Homology, Amino Acid, pubmed-meshheading:8547174-Steroid Isomerases, pubmed-meshheading:8547174-Structure-Activity Relationship, pubmed-meshheading:8547174-Trout
pubmed:year
1995
pubmed:articleTitle
Structure-function relationships and molecular genetics of the 3 beta-hydroxysteroid dehydrogenase gene family.
pubmed:affiliation
Medical Research Council Group in Molecular Endocrinology, CHUL Research Center, Québec, Canada.
pubmed:publicationType
Journal Article, Comparative Study