**3. ACE2**

ACE2 is a cell surface protein, a metalloproteinase and an ectoenzyme which is an obligatory receptor for SARS-CoV and SARS-CoV-2. The affinity of SARS-CoV-2 to ACE2 is ten times higher than that of SARS-CoV which partly explains its higher pathogenicity [18]. It was discovered in 2000 by two independent groups of researchers while searching for human ACE homologues [19, 20]. The gene for ACE2 in humans is located in Xp22 and has 18 exons, a majority of which are similar to the exons of the ACE gene [21]. Despite ACE2 exhibiting 42% sequence identify and 61% sequence similarity with ACE, the two enzymes show enormous variations (**Table 1**) [27].


#### **Table 1.**

*The comparison between ACE and ACE2 is given in* **Table 1** *[22–26].*

Since the 20 years of its discovery, ACE2 was found to have a multitude of physiological and pathological functions based on its three fundamental actions viz. negative regulation of renin-angiotensin system [RAS], facilitation of amino acid transport in the intestine, and surface receptor for SARS-CoV and SARS-CoV-2. ACE2 is mainly expressed in the lungs, intestine, liver, heart, kidneys, testes, and brain. In the brain, it is expressed in neurons, astrocytes and oligodendrocytes, and in ventricles, substantia nigra, hypothalamus, hippocampus, middle temporal gyrus, posterior cingulate cortex, nuclei in pons—the nucleus of tractus solitarius and pre-Bötzinger complex and olfactory bulb [21, 28]. ACE2 expression is higher in astrocytes, astrocytic foot processes, pericytes, and endothelial cells which form the key components of the blood–brain barrier [29]. In the olfactory epithelium, its expression is higher in the supporting sustentacular cells than in olfactory sensory neurons [30]. The sites of ACE2 expression are given in **Table 2** [31].

#### **3.1 Structure**

ACE2 is a type 1 integral membrane protein that includes a short cytoplasmic C-terminus, a transmembrane region, collectrin, and N-terminal ectodomain. Zincbinding motifs, HEMGH forms the active site of the enzyme. N-terminal domain

*Does COVID-19 Affect Adult Neurogenesis? A Neurochemical Perspective DOI: http://dx.doi.org/10.5772/intechopen.101179*


#### **Table 2.**

*Sites of ACE2 expression.*

has a claw-shaped protease domain which is the binding site of receptor-binding domain [RBD] of SARS-CoV and SARS-CoV-2. N terminus is homologous to ACE and is a carboxypeptidase that metabolises peptides like angiotensin II, kinins, apelin-13, apelin-36, neurotensin 1–13, kinetensin, and morphins, and C terminus is homologous to collectrin which is involved in the trafficking of neutral amino acid transporter [B[o]AT1] in the intestinal epithelium [32].
