Developmental biology of angiotensin-converting enzyme
- PDF / 1,058,008 Bytes
- 8 Pages / 596 x 842 pts (A4) Page_size
- 93 Downloads / 215 Views
Developmental biology review Developmental biology of angiotensin-converting enzyme Igor V. Yosipiv and Samir S. El-Dahr Section of Pediatric Nephrology, Department of Pediatrics, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, Louisiana 70112, USA Received March 18, 1997; accepted June 17, 1997
Abstract. Molecular, biochemical, and evolutionary studies indicate that somatic angiotensin-converting enzyme (ACE) is developmentally regulated in a tissue-specific manner. However, many important questions remain unanswered. For example, the regulatory mechanisms that control the cell- and stage-specific expression of ACE remain largely unknown. The nature, location, and role of the enzyme involved in the release of plasma membrane-anchored ACE have not been elucidated. Although the expression and localization of ACE are developmentally regulated, the physiological implications of these changes in segmental nephron differentiation remain to be elucidated. Investigations of the cellular and molecular mechanisms mediating the developmental co-regulation of the renin-angiotensin and Kallikrein-kinin system by ACE are a formidable challenge for future research.
Fig. 1. The renin-angiotensin and kallikrein-kinin systems. ACE, Angiotensin-converting enzyme; NO, nitric oxide; LMW, low molecular weight
Key words: Angiotensin-converting enzyme ± Developmental biology
Biochemistry of ACE
Introduction Angiotensin-converting enzyme (ACE or kininase II) is a phylogenetically conserved protein that plays a central role in the control of circulating and tissue levels of angiotensin II (AII) and bradykinin (BK). Ontogenetic studies have demonstrated that both of these peptides regulate renal function and growth during normal development. The present article reviews recent advances in our understanding of the developmental biology of ACE in the context of its dual modulation of the renin-angiotensin and kallikrein-kinin systems.
Correspondence to: I. V. Yosipiv
ACE (EC 3.4.15.1) is a zinc metalloproteinase that is involved in the posttranslational processing of many polypeptides, the most notable of which are AI and BK (Fig. 1) [1]. There are two isozymes of ACE, somatic and germinal (testicular), transcribed from a single gene by differential utilization of two distinct promoters [2]. Human somatic ACE has a molecular weight of 140 ± 160 kilodaltons (kDa) containing 1,306 amino acids, whereas germinal ACE has a molecular weight of 80 kDa and contains 732 amino acids. In vitro mutagenesis studies demonstrated that somatic ACE is composed of two putative functional catalytic sites both dependent on a zinc cofactor [3]. Although both domains possess dipeptidyl carboxypeptidase activity towards AI and BK, they display different catalytic constants for these substrates. Both domains contain a high-affinity binding site for ACE inhibitors [4]. The germinal ACE sequence corresponds to the carboxyl(COOH)-terminal domain of somatic ACE [5, 6]. Accordingly, it contains only one of the two catalytic sites identified in
Data Loading...
