Linked Life Data

7744780

Source:http://linkedlifedata.com/resource/pubmed/id/7744780

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
1995-6-15
pubmed:databankReference
pubmed:abstractText
Angiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency > 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11430-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.
pubmed:affiliation
Howard Hughes Medical Institute, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.
pubmed:publicationType
Journal Article, Comparative Study, Case Reports, Research Support, Non-U.S. Gov't