PMID- 7744780
OWN - NLM
STAT- MEDLINE
DCOM- 19950615
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 270
IP  - 19
DP  - 1995 May 12
TI  - A mutation of angiotensinogen in a patient with preeclampsia leads to altered 
      kinetics of the renin-angiotensin system.
PG  - 11430-6
AB  - 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.
FAU - Inoue, I
AU  - Inoue I
AD  - Howard Hughes Medical Institute, University of Utah Health Sciences Center, Salt 
      Lake City, UT 84112, USA.
FAU - Rohrwasser, A
AU  - Rohrwasser A
FAU - Helin, C
AU  - Helin C
FAU - Jeunemaitre, X
AU  - Jeunemaitre X
FAU - Crain, P
AU  - Crain P
FAU - Bohlender, J
AU  - Bohlender J
FAU - Lifton, R P
AU  - Lifton RP
FAU - Corvol, P
AU  - Corvol P
FAU - Ward, K
AU  - Ward K
FAU - Lalouel, J M
AU  - Lalouel JM
LA  - eng
SI  - GENBANK/S78223
PT  - Case Reports
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Peptides)
RN  - 11002-13-4 (Angiotensinogen)
RN  - 47E5O17Y3R (Phenylalanine)
RN  - EC 3.4.23.15 (Renin)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Angiotensinogen/*genetics/metabolism
MH  - Base Sequence
MH  - Female
MH  - Humans
MH  - Kinetics
MH  - Leucine
MH  - Molecular Sequence Data
MH  - Oligodeoxyribonucleotides
MH  - Peptides/chemical synthesis/metabolism
MH  - Phenylalanine
MH  - *Point Mutation
MH  - Pre-Eclampsia/*blood
MH  - Pregnancy
MH  - Renin/*metabolism
MH  - *Renin-Angiotensin System
MH  - Substrate Specificity
EDAT- 1995/05/12 00:00
MHDA- 1995/05/12 00:01
CRDT- 1995/05/12 00:00
PHST- 1995/05/12 00:00 [pubmed]
PHST- 1995/05/12 00:01 [medline]
PHST- 1995/05/12 00:00 [entrez]
AID - S0021-9258(17)50217-3 [pii]
AID - 10.1074/jbc.270.19.11430 [doi]
PST - ppublish
SO  - J Biol Chem. 1995 May 12;270(19):11430-6. doi: 10.1074/jbc.270.19.11430.