title: A modern understanding of the traditional and nontraditional biological functions of angiotensin-converting enzyme.
abstract: Angiotensin-converting enzyme (ACE) is a zinc-dependent peptidase responsible for converting angiotensin I into the vasoconstrictor angiotensin II. However, ACE is a relatively nonspecific peptidase that is capable of cleaving a wide range of substrates. Because of this, ACE and its peptide substrates and products affect many physiologic processes, including blood pressure control, hematopoiesis, reproduction, renal development, renal function, and the immune response. The defining feature of ACE is that it is composed of two homologous and independently catalytic domains, the result of an ancient gene duplication, and ACE-like genes are widely distributed in nature. The two ACE catalytic domains contribute to the wide substrate diversity of ACE and, by extension, the physiologic impact of the enzyme. Several studies suggest that the two catalytic domains have different biologic functions. Recently, the X-ray crystal structure of ACE has elucidated some of the structural differences between the two ACE domains. This is important now that ACE domain-specific inhibitors have been synthesized and characterized. Once widely available, these reagents will undoubtedly be powerful tools for probing the physiologic actions of each ACE domain. In turn, this knowledge should allow clinicians to envision new therapies for diseases not currently treated with ACE inhibitors.
authors.affiliation: Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Davis 2021, Los Angeles, CA 90048, USA. kbernst@cshs.org
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Bernstein
authors.forename: Frank S
authors.initials: FS
authors.lastname: Ong
authors.forename: Wendell-Lamar B
authors.initials: WL
authors.lastname: Blackwell
authors.forename: Kandarp H
authors.initials: KH
authors.lastname: Shah
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Giani
authors.forename: Romer A
authors.initials: RA
authors.lastname: Gonzalez-Villalobos
authors.forename: Xiao Z
authors.initials: XZ
authors.lastname: Shen
authors.forename: Sebastien
authors.initials: S
authors.lastname: Fuchs
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Touyz
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D049673:History, 20th Century; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000266:history / Q000502:physiology*; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D012083:Renin / Q000502:physiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A; D012083:Renin