Different in vivo functions of the two catalytic domains of angiotensin-converting enzyme (ACE).
Angiotensin-converting enzyme (ACE) can cleave angiotensin I, bradykinin, neurotensin and many other peptide substrates in vitro. In part, this is due to the structure of ACE, a protein composed of two independent catalytic domains. Until very recently, little was known regarding the specific in vivo role of each ACE domain, and they were commonly regarded as equivalent. This is not true, as shown by mouse models with a genetic inactivation of either the ACE N- or C-domain. In vivo, most angiotensin II is produced by the ACE C-domain. Some peptides, such as the anti-fibrotic peptide AcSDKP, are substrates only of the ACE N-domain. Knowing the in vivo role of each ACE domain has great significance for developing ACE domain-specific inhibitors and for understanding the full effects of the anti-ACE pharmaceuticals in widespread clinical use.
Department of Biomedical Sciences, Cedars-Sinai Medical Center, 110 N. George Burns Rd, Los Angeles, CA 90048, USA.
Kenneth E
KE
Bernstein
Xiao Z
XZ
Shen
Romer A
RA
Gonzalez-Villalobos
Sandrine
S
Billet
Derick
D
Okwan-Duodu
Frank S
FS
Ong
Sebastien
S
Fuchs
D000818:Animals; D001794:Blood Pressure; D020134:Catalytic Domain / Q000502:physiology*; D005298:Fertility; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000378:metabolism
D009842:Oligopeptides; D007703:Peptidyl-Dipeptidase A; C058504:goralatide