**3. Cytochrome P450 11B2 (***CYP11B2***)**

#### **3.1 Reaction catalyzed**

*CYP11B2* enzyme is located in the inner mitochondrial membrane. Aldosterone synthesis from 11-deoxycorticosterone is catalyzed by *CYP11B2* enzyme, more commonly referred to as aldosterone synthase, which catalyzes three sequential reactions, each utilizing one molecule of NADPH, one molecule of oxygen, and the mitochondrial electron transfer system. The three sequential reactions are as follows: the 11β-hydroxylation of 11 deoxycorticosterone, the hydroxylation of carbon 18, followed by oxidation of the carbon 18 hydroxyl group to yield the carbon 18 aldehyde group resulting in the formation of aldosterone (**Figure 3**) [19].

#### **3.2 Molecular structure**

*CYP11B2* gene is located on human chromosome 8q21-22. It consists of nine exons, eight introns, and comprises about 7 kb (**Figure 4**). Its coding region is 95% identical, and its intronic region is 90% identical with *CYP11B1*. However, its 5′ untranslated region is different from that of *CYP11B1* gene, thus accounting for the differences in regulation and expression pattern for each gene [20].

#### **3.3 Protein structure**

The human *CYP11B2* proteins are located in the inner mitochondrial membrane and consist of 503 amino acids, including a 24-residue N-terminal mitochondrial targeting sequence. At the protein level, the enzyme is 93% homologous with *CYP11B1* reflecting its shared 11β-hydroxylase and 18-hydroxylation activity. Only 37 amino acids differ between them which accounts for their different functions. Although *CYP11B1* and *B2* consist of the same number of amino acid, the apparent molecular mass of the human enzymes was reported as 51 and 49 kDa, respectively [20].

**21**

**Figure 3.**

**Figure 4.**

**3.4 Tissue-specific expression**

to ACTH, angiotensin II, K+

sively in adrenal zona glomerulosa cells [21].

*Schematic diagram of the exonic-intronic arrangement of the CYP11B2 genes.*

**3.5 Regulation of** *CYP11B2* **expression**

*Enzymatic reactions catalyzed by CYP11B2 enzyme.*

Expression of *CYP11B2* is limited to the adrenal cortex and appears to be exclu-

Adrenal steroidogenesis is under both acute and chronic regulation by tropic hormones. The acute response occurs within minutes and involves the mobilization of cholesterol from intracellular stores to the mitochondrial membrane in response

, and their respective intracellular messenger pathways.

*Aldosterone Synthase Gene (*CYP11B2*) Polymorphisms and Enhanced Cardiovascular Risk*

*DOI: http://dx.doi.org/10.5772/intechopen.89133*

*Aldosterone Synthase Gene (*CYP11B2*) Polymorphisms and Enhanced Cardiovascular Risk DOI: http://dx.doi.org/10.5772/intechopen.89133*

#### **Figure 3.**

*The Recent Topics in Genetic Polymorphisms*

and sympathetic tone [4].

**3.1 Reaction catalyzed**

**3.2 Molecular structure**

**3.3 Protein structure**

respectively [20].

**3. Cytochrome P450 11B2 (***CYP11B2***)**

alone [18].

existing ion channels or increasing their number [14].

myocytes, endocardium of the heart, brain, vascular smooth muscle, liver, and leukocytes [12]. The main action of aldosterone is stimulation of sodium reabsorption in the kidney and at other secretory epithelial sites with excretion of potassium and hydrogen ions [13] possibly mediated via increasing the opening periods of the

In cardiovascular system, aldosterone promotes myocardial hypertrophy and fibrosis via increasing collagen I synthesis in cardiac fibroblasts and also elevating endothelin receptor numbers that further increases collagen synthesis [15]. So, increased expression of mineralocorticoid receptors in the heart may result in left-ventricular hypertrophy in normotensive subjects [16]. Aldosterone also stimulates vascular constriction via enhancing the pressor response to catecholamines and impairing the vasodilatory response to acetylcholine or by upregulation of angiotensin II receptors [4]. Also, aldosterone excess can trigger collagen deposition in blood vessels, enhancing vascular remodeling and reducing compliance [17]. In the CNS, it appears to regulate blood pressure, salt appetite,

Under normal circumstances, it is likely that cardiac MRs are occupied by glucocorticoid due to its higher circulating concentration exerting antagonistic effect attenuating the rise in blood pressure and the cardiac fibrosis caused by aldosterone

*CYP11B2* enzyme is located in the inner mitochondrial membrane. Aldosterone synthesis from 11-deoxycorticosterone is catalyzed by *CYP11B2* enzyme, more commonly referred to as aldosterone synthase, which catalyzes three sequential reactions, each utilizing one molecule of NADPH, one molecule of oxygen, and the mitochondrial electron transfer system. The three sequential reactions are as follows: the 11β-hydroxylation of 11 deoxycorticosterone, the hydroxylation of carbon 18, followed by oxidation of the carbon 18 hydroxyl group to yield the carbon 18 aldehyde group resulting in the formation of aldosterone (**Figure 3**) [19].

*CYP11B2* gene is located on human chromosome 8q21-22. It consists of nine exons, eight introns, and comprises about 7 kb (**Figure 4**). Its coding region is 95% identical, and its intronic region is 90% identical with *CYP11B1*. However, its 5′ untranslated region is different from that of *CYP11B1* gene, thus accounting for the

The human *CYP11B2* proteins are located in the inner mitochondrial membrane and consist of 503 amino acids, including a 24-residue N-terminal mitochondrial targeting sequence. At the protein level, the enzyme is 93% homologous with *CYP11B1* reflecting its shared 11β-hydroxylase and 18-hydroxylation activity. Only 37 amino acids differ between them which accounts for their different functions. Although *CYP11B1* and *B2* consist of the same number of amino acid, the apparent molecular mass of the human enzymes was reported as 51 and 49 kDa,

differences in regulation and expression pattern for each gene [20].

**20**

*Enzymatic reactions catalyzed by CYP11B2 enzyme.*

**Figure 4.** *Schematic diagram of the exonic-intronic arrangement of the CYP11B2 genes.*

### **3.4 Tissue-specific expression**

Expression of *CYP11B2* is limited to the adrenal cortex and appears to be exclusively in adrenal zona glomerulosa cells [21].

### **3.5 Regulation of** *CYP11B2* **expression**

Adrenal steroidogenesis is under both acute and chronic regulation by tropic hormones. The acute response occurs within minutes and involves the mobilization of cholesterol from intracellular stores to the mitochondrial membrane in response to ACTH, angiotensin II, K+ , and their respective intracellular messenger pathways. The chronic response takes several hours and involves the transcription of the genes encoding the steroidogenic enzymes [22].

## *3.5.1 Signaling pathways that regulate aldosterone production*
