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Known and little-known functions of angiotensin-converting enzyme

DOI 10.18127/j20700997-201904-03


A.P. Bobkov – Resident, Department of Internal Medicine, Faculty of Base Medicine, Lomonosov Moscow State University
L.Ya. Frantsuzevich – Resident, Department of Internal Medicine, Faculty of Base Medicine, Lomonosov Moscow State University
T.N. Krasnova – Ph.D. (Med.), Associate Professor, Head of the Department of Internal Medicine, Faculty of Base Medicine, Lomonosov Moscow State University
L.M. Samokhodskaya – Ph.D. (Med.), Associate Professor, Head of the Department of Laboratory Diagnostics, Medical Scientific-Educational Center of Lomonosov Moscow State University

The paper presents a survey of modern literature dedicated to different functions of the angiotensin-converting enzyme (ACE). ACE should be considered to some extent undervalued in clinical practice as a target as a diagnostic marker.
ACE is a non-specific zinc-dependent membrane-bound dipeptidyl carboxypeptidase. The active center of ACE is represented by a highly conservative sequence of amino acids His-Glu-X-X-His (HEXXH). The enzyme enters in biological fluids by shedding from the cell surface. The unknown protein is called ACE-secretase is responsible for ACE shedding from the surface of a cell to biological fluids.
ACE is presented in the body by a single-domain, or testicular, and double-domain, or somatic, isoforms. Testicular and somatic ACE isoforms are transcribed from the ACE gene by alternative splicing.
The majority of physiological effects and functions of ACE are directly related to the products of enzyme-catalyzed reactions, and its low specificity allows the enzyme to be widely involved in various processes of an organism.
Currently, the role of ACE in hematopoiesis is described. Investigators detected ACE processes AcSDKP, which INHIBITS differentiation and proliferation of bone marrow stem cells. The effect of ACE on the cardiovascular system is explained effects of angiotensin-2, which is a well-known product of reaction catalyzing ACE. ACE influence on the respiratory system is mediated by angiotensin-2 and bradykinin (substrates of ACE). We should also take into account the role of ACE in the processing of antigens and cell signaling because the enzyme performs these functions directly (without the participation of its reaction products).
Based on the functions of ACE, in particular, AcSDKP processing, the selective ACE N-domain inhibitor (RXP407) are developed. RXP407 has the potential to be used in clinical practice for cancer patients undergoing radiotherapy. The group of researchers quantified the degree of ACE inhibition using different substrates (ZPHL and HHL) of ACE. A new method using for detection of the conformation of the enzyme (conformational fingerprinting) has successfully described the differences of the enzyme spatial organization in tissues such as the lung, heart, prostate, immune cells, etc. Moreover, ACE conformational differences are found in the blood of patients with sarcoidosis, Gaucher's disease, and control group.
New methods and ideas of exploitation of ACE mentioned in the article are not common in clinical practice, but have serious prospects for use.

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