PMID- 10336644
OWN - NLM
STAT- MEDLINE
DCOM- 19990624
LR  - 20190620
IS  - 0014-2956 (Print)
IS  - 0014-2956 (Linking)
VI  - 262
IP  - 2
DP  - 1999 Jun
TI  - Hydrolysis by somatic angiotensin-I converting enzyme of basic dipeptides from a 
      cholecystokinin/gastrin and a LH-RH peptide extended at the C-terminus with 
      gly-Arg/Lys-arg, but not from diarginyl insulin.
PG  - 569-74
AB  - Endoproteolytic cleavage of protein prohormones often generates intermediates 
      extended at the C-terminus by Arg-Arg or Lys-Arg, the removal of which by a 
      carboxypeptidase (CPE) is normally an important step in the maturation of many 
      peptide hormones. Recent studies in mice that lack CP activity indicate the 
      existence of alternative tissue or plasma enzymes capable of removing C-terminal 
      basic residues from prohormone intermediates. Using inhibitors of angiotensin 
      I-converting enzyme (ACE) and CP, we show that both these enzymes in mouse serum 
      can remove the basic amino acids from the C-terminus of CCK5-GRR and LH-RH-GKR, 
      but only CP is responsible for converting diarginyl insulin to insulin. ACE 
      activity removes C-terminal dipeptides to generate the Gly-extended peptides, 
      whereas CP hydrolysis gives rise to CCK5-GR and LH-RH-GK, both of which are 
      susceptible to the dipeptidyl carboxypeptidase activity of ACE. Somatic ACE has 
      two similar protein domains (the N-domain and the C-domain), each with an active 
      site that can display different substrate specificities. CCK5-GRR is a 
      high-affinity substrate for both the N-domain and C-domain active sites of human 
      sACE (Km of 9.4 microm and 9.0 microm, respectively) with the N-domain showing 
      greater efficiency (kcat : Km ratio of 2.6 in favour of the N-domain). We 
      conclude that somatic forms of ACE should be considered as alternatives to CPs 
      for the removal of basic residues from some Arg/Lys-extended peptides.
FAU - Isaac, R E
AU  - Isaac RE
AD  - School of Biology, University of Leeds, UK. r.e.isaac@leeds.ac.uk
FAU - Michaud, A
AU  - Michaud A
FAU - Keen, J N
AU  - Keen JN
FAU - Williams, T A
AU  - Williams TA
FAU - Coates, D
AU  - Coates D
FAU - Wetsel, W C
AU  - Wetsel WC
FAU - Corvol, P
AU  - Corvol P
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 0 (Dipeptides)
RN  - 0 (Gastrins)
RN  - 0 (Insulin)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 68859-20-1 (insulin, Arg(B31,B32)-)
RN  - 9011-97-6 (Cholecystokinin)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - K3Z4F929H6 (Lysine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Animals
MH  - Arginine/chemistry
MH  - Cholecystokinin/*chemistry
MH  - Dipeptides/*metabolism
MH  - Female
MH  - Gastrins/*chemistry
MH  - Glycine/chemistry
MH  - Gonadotropin-Releasing Hormone/*chemistry
MH  - Humans
MH  - Hydrolysis
MH  - Insulin/*analogs & derivatives/chemistry
MH  - Lysine/chemistry
MH  - Mice
MH  - Peptidyl-Dipeptidase A/*metabolism
MH  - Substrate Specificity
EDAT- 1999/05/21 00:00
MHDA- 1999/05/21 00:01
CRDT- 1999/05/21 00:00
PHST- 1999/05/21 00:00 [pubmed]
PHST- 1999/05/21 00:01 [medline]
PHST- 1999/05/21 00:00 [entrez]
AID - 10.1046/j.1432-1327.1999.00419.x [doi]
PST - ppublish
SO  - Eur J Biochem. 1999 Jun;262(2):569-74. doi: 10.1046/j.1432-1327.1999.00419.x.