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Molecular and Physiological Aspects of Angiotensin I Converting Enzyme

Francois Alhenc‐Gelas, Pierre Corvol

10.1002/cphy.cp070303

Source: Supplement 22: Handbook of Physiology, The Endocrine System, Endocrine Regulation of Water and Electrolyte Balance

Originally published: 2000

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Distribution
1.1 Somatic Angiotensin‐Converting Enzyme
1.2 Germinal Angiotensin‐Converting Enzyme
2 Catalytic Properties
2.1 Angiotensin‐Converting Enzyme Is a Zinc Metallopeptidase
2.2 Substrate Specificity
2.3 Anion Activation
3 Molecular Structure of Angiotensin‐Converting Enzyme
3.1 Somatic Angiotensin‐Converting Enzyme
3.2 Germinal Angiotensin‐Converting Enzyme
4 Two Angiotensin‐Converting Enzyme Active Sites: Identification of Essential Residues
5 Differences in the Characteristics of the N and C domains
5.1 Chloride Activation
5.2 Substrate Specificity
5.3 Angiotensin‐Converting Enzyme Inhibitors
6 Structure of the Angiotensin‐Converting Enzyme Gene
7 Mechanism of Angiotensin‐Converting Enzyme Anchorage and Solubilization
8 Regulation of Angiotensin‐Converting Enzyme Gene Expression in Somatic And Germinal Cells
9 Induction of Angiotensin‐Converting Enzyme Gene Expression in Physiological and Pathological Situations
10 Genetic Polymorphism of Angiotensin‐Converting Enzyme Levels in Humans
11 Association of the Genetic Polymorphism of Angiotensin‐Converting Enzyme Levels with Disease
12 Physiological Role of Angiotensin‐Converting Enzyme
Figure 1. Figure 1.

Schematic representation of the human angiotensin‐converting enzyme (ACE) gene on chromosome 17q23, its somatic and germinal transcripts, and their protein products. P1 and P2 indicate the location of the somatic and testicular promoters, respectively. Arrows indicate sites of transcription initiation. Hatched areas in somatic ACE indicate the two regions displaying greater than 60% sequence homology and carrying one active site each. HEMGH indicates position of consensus sequences of zinc metallopeptidases containing the two zinc‐coordinating histidines and an essential glutamic acid in these active sites.
Figure 2. Figure 2.

Schematic respresentation of human somatic angiotensin‐converting enzyme with location of some critical amino acids identified by protein sequencing or site‐directed mutagenesis. White box on the left is the signal peptide. Hatched areas represent the two homologous domains, each with one active site. The position of the zinc‐coordinating amino acids and other essential catalytic residues in these active sites is indicated above the graph. Bottom: Detail of the carboxy‐terminal extremity with the transmembrane‐anchoring sequence and the location of the cleavage site (arrow) for the release of the soluble enzyme.
Figure 3. Figure 3.

Insertion (I)/deletion (D) angiotensin‐converting enzyme polymorphism of intron 16 of the angiotensin‐converting enzyme (ACE) gene and association with plasma and membrane‐bound (T lymphocyte) ACE levels. A: Schematic representation of the 3′ part of intron 16 and the 5′ part of exon 17 with the polymorphic Alu sequence (hatched segment). Arrows indicate position of flanking and sequence‐specific oligonucleotide primers used for genotyping. B: Results of genotyping by a nested polymerase chain reaction amplification technique using these primers. C: Association of serum ACE levels with genotype in healthy subjects (P <0.001). D: Association of T‐lymphocyte ACE levels with genotype (P <0.01). From Rigat et al. 177, Costerousse et al. 37, and Marre et al. 140 with permission.


Figure 1.

Schematic representation of the human angiotensin‐converting enzyme (ACE) gene on chromosome 17q23, its somatic and germinal transcripts, and their protein products. P1 and P2 indicate the location of the somatic and testicular promoters, respectively. Arrows indicate sites of transcription initiation. Hatched areas in somatic ACE indicate the two regions displaying greater than 60% sequence homology and carrying one active site each. HEMGH indicates position of consensus sequences of zinc metallopeptidases containing the two zinc‐coordinating histidines and an essential glutamic acid in these active sites.



Figure 2.

Schematic respresentation of human somatic angiotensin‐converting enzyme with location of some critical amino acids identified by protein sequencing or site‐directed mutagenesis. White box on the left is the signal peptide. Hatched areas represent the two homologous domains, each with one active site. The position of the zinc‐coordinating amino acids and other essential catalytic residues in these active sites is indicated above the graph. Bottom: Detail of the carboxy‐terminal extremity with the transmembrane‐anchoring sequence and the location of the cleavage site (arrow) for the release of the soluble enzyme.



Figure 3.

Insertion (I)/deletion (D) angiotensin‐converting enzyme polymorphism of intron 16 of the angiotensin‐converting enzyme (ACE) gene and association with plasma and membrane‐bound (T lymphocyte) ACE levels. A: Schematic representation of the 3′ part of intron 16 and the 5′ part of exon 17 with the polymorphic Alu sequence (hatched segment). Arrows indicate position of flanking and sequence‐specific oligonucleotide primers used for genotyping. B: Results of genotyping by a nested polymerase chain reaction amplification technique using these primers. C: Association of serum ACE levels with genotype in healthy subjects (P <0.001). D: Association of T‐lymphocyte ACE levels with genotype (P <0.01). From Rigat et al. 177, Costerousse et al. 37, and Marre et al. 140 with permission.

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Article Title: Molecular and Physiological Aspects of Angiotensin I Converting Enzyme
 

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Francois Alhenc‐Gelas, Pierre Corvol. Molecular and Physiological Aspects of Angiotensin I Converting Enzyme. Compr Physiol 2011, Supplement 22: Handbook of Physiology, The Endocrine System, Endocrine Regulation of Water and Electrolyte Balance: 81-103. First published in print 2000. doi: 10.1002/cphy.cp070303