PMID- 10536878
OWN - NLM
STAT- MEDLINE
DCOM- 19991202
LR  - 20191103
IS  - 8755-5093 (Print)
IS  - 1026-5457 (Linking)
VI  - 14
IP  - 6
DP  - 1999
TI  - Mixed-type inhibition of pulmonary angiotensin I-converting enzyme by captopril, 
      enalaprilat and ramiprilat.
PG  - 447-56
AB  - We have compared at the enzymological level pulmonary angiotensin I-converting
      enzymes (ACE) purified to electrophoretic homogeneity from four mammalians
      species: pig, rat, monkey and human. Using both substrates
      hippuryl-histidyl-leucine and furylacryloyl-phenylalanyl-glycyl-glycine in
      steady-state conditions, all the ACEs exhibited Michaelis kinetics with identical
      Michaelis constants, maximal velocities, optimal pH and optimal activating
      chloride-concentrations. The apparent inhibitory constant was higher for
      Captopril than for Enalaprilat and even more so for Ramiprilat irrespective of
      the origin of ACE and the substrate used. Although these inhibitors have been
      described as competitive inhibitors, Lineweaver-Burk plots were not in accordance
      with a simple competitive model; moreover, Dixon plots were rather characteristic
      of non-competitive inhibition. These data emphasize the hypothesis that ACE
      inhibitors act with mixed-type inhibition, which is consistent with their
      slow-tight binding to the ACE active center, also with binding of chloride on a
      critical lysine residue leading to a potential conformational change, and finally
      with the fact that ACE has two domains, each bearing one catalytic site. On the
      other hand, as identical kinetic parameters were obtained on the different ACE
      preparations, results from animal models should allow the extrapolation to
      humans, in particular for investigations on both renin-angiotensin and
      kallikrein-kinin systems, and on their inhibition.
FAU - Baudin, B
AU  - Baudin B
AD  - Service de Biochimie A, Hopital Saint-Antoine, Paris, France.
      bruno.baudin@sat.ap-hop-paris.fr
FAU - Beneteau-Burnat, B
AU  - Beneteau-Burnat B
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - J Enzyme Inhib
JT  - Journal of enzyme inhibition
JID - 8709734
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 6N5U4QFC3G (ramiprilat)
RN  - 9G64RSX1XD (Captopril)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - GV0O7ES0R3 (Enalaprilat)
RN  - L35JN3I7SJ (Ramipril)
SB  - IM
MH  - Angiotensin-Converting Enzyme Inhibitors/*pharmacology
MH  - Animals
MH  - Binding, Competitive
MH  - Captopril/pharmacology
MH  - Enalaprilat/pharmacology
MH  - Humans
MH  - Kinetics
MH  - Lung/*enzymology
MH  - Macaca fascicularis
MH  - Peptidyl-Dipeptidase A/*metabolism
MH  - Ramipril/analogs & derivatives/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Swine
EDAT- 1999/10/28 00:00
MHDA- 1999/10/28 00:01
CRDT- 1999/10/28 00:00
PHST- 1999/10/28 00:00 [pubmed]
PHST- 1999/10/28 00:01 [medline]
PHST- 1999/10/28 00:00 [entrez]
AID - 10.3109/14756369909030335 [doi]
PST - ppublish
SO  - J Enzyme Inhib. 1999;14(6):447-56. doi: 10.3109/14756369909030335.