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Review ArticleReview Article

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

Kenneth E. Bernstein, Frank S. Ong, Wendell-Lamar B. Blackwell, Kandarp H. Shah, Jorge F. Giani, Romer A. Gonzalez-Villalobos, Xiao Z. Shen and Sebastien Fuchs
Rhian M. Touyz, ASSOCIATE EDITOR
Pharmacological Reviews January 2013, 65 (1) 1-46; DOI: https://doi.org/10.1124/pr.112.006809
Kenneth E. Bernstein
Department of Biomedical Sciences and Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California
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Frank S. Ong
Department of Biomedical Sciences and Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California
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Wendell-Lamar B. Blackwell
Department of Biomedical Sciences and Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California
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Kandarp H. Shah
Department of Biomedical Sciences and Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California
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Jorge F. Giani
Department of Biomedical Sciences and Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California
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Romer A. Gonzalez-Villalobos
Department of Biomedical Sciences and Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California
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Xiao Z. Shen
Department of Biomedical Sciences and Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California
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Sebastien Fuchs
Department of Biomedical Sciences and Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California
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Rhian M. Touyz
Department of Biomedical Sciences and Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California
Roles: ASSOCIATE EDITOR
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This article has a correction. Please see:

  • Correction to: “A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme” - January 01, 2013

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.

Footnotes

  • The authors' laboratories are supported by grants from the National Institutes of Health National Heart, Lung and Blood Institute [Grants R01HL110353 (to K.E.B.), F32H105036 (to F.S.O.)]; and the National Institutes of Health National Institute for Diabetes, Digestive and Kidney Disease [Grants T32DK007770 (to W.-L.B.B.), R00DK083455 (to R.A.G.-V.)]. F.S.O. is also supported by the Cedars-Sinai Medical Center Clinical and Translational Science Institute Clinical Scholars Award.

  • dx.doi.org/10.1124/pr.112.006809.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 65 (1)
Pharmacological Reviews
Vol. 65, Issue 1
1 Jan 2013
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Review ArticleReview Article

A Modern Understanding of ACE

Kenneth E. Bernstein, Frank S. Ong, Wendell-Lamar B. Blackwell, Kandarp H. Shah, Jorge F. Giani, Romer A. Gonzalez-Villalobos, Xiao Z. Shen and Sebastien Fuchs
Pharmacological Reviews January 1, 2013, 65 (1) 1-46; DOI: https://doi.org/10.1124/pr.112.006809

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Review ArticleReview Article

A Modern Understanding of ACE

Kenneth E. Bernstein, Frank S. Ong, Wendell-Lamar B. Blackwell, Kandarp H. Shah, Jorge F. Giani, Romer A. Gonzalez-Villalobos, Xiao Z. Shen and Sebastien Fuchs
Pharmacological Reviews January 1, 2013, 65 (1) 1-46; DOI: https://doi.org/10.1124/pr.112.006809
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  • Article
    • Abstract
    • I. Introduction
    • II. Renin Versus Angiotensin-Converting Enzyme
    • III. The Discovery and Physical Properties of Angiotensin-Converting Enzyme
    • IV. Function of Angiotensin-Converting Enzyme
    • V. Evolutionary Implications of Two Angiotensin-Converting Enzyme Catalytic Domains
    • VI. Differences between the N- and C-domains of Angiotensin-Converting Enzyme
    • VII. Angiotensin-Converting Enzyme Inhibitors
    • VIII. Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism
    • IX. Conclusions
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
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