Angiotensin-Converting Enzyme 2, or ACE2, is a protein found throughout the human body. It plays a significant role in various biological processes and is a naturally occurring component of human physiology. While recently gaining attention for its involvement with certain viruses, ACE2 helps maintain balance within the body’s internal systems.
Understanding ACE2
ACE2 operates as both an enzyme and a receptor within the body. As an enzyme, it performs specific chemical reactions by breaking down certain molecules. As a receptor, it acts like a docking station on the surface of cells, allowing other molecules to bind and trigger cellular responses.
This protein is found in many human tissues, including the lungs, heart, arteries, kidneys, liver, and gastrointestinal tract. It is abundant in the epithelial cells that line these organs. Structurally, ACE2 is a type I integral membrane glycoprotein, spanning the cell membrane with an attached sugar component. It is composed of 805 amino acids and has a molecular weight typically ranging from 120 to 170 kDa, depending on how it’s modified with sugars. The protein contains an N-terminal peptidase domain for its enzymatic activity and a C-terminal collectrin-like domain for interacting with other proteins.
ACE2’s Normal Functions in the Body
ACE2 plays an important role in regulating blood pressure and protecting organs as part of the Renin-Angiotensin System (RAS). The RAS is a complex hormonal system that helps control blood pressure, fluid balance, and electrolyte levels. Within this system, ACE2 acts as a counter-regulatory enzyme to Angiotensin-Converting Enzyme (ACE).
While ACE converts angiotensin I into angiotensin II, a molecule that constricts blood vessels and increases blood pressure, ACE2 performs the opposite action. It breaks down angiotensin II into angiotensin-(1-7), a peptide that promotes vasodilation (widening of blood vessels) and has anti-inflammatory effects. This balance between angiotensin II and angiotensin-(1-7) is important for maintaining stable blood pressure and protecting organs like the heart and kidneys from damage caused by excessive angiotensin II activity.
Beyond blood pressure regulation, ACE2 also participates in other bodily functions. It helps transport neutral amino acids in the gut. This role highlights ACE2’s importance in cellular processes beyond its cardiovascular functions. Its presence in various tissues contributes to maintaining overall bodily homeostasis.
ACE2 and Viral Entry
ACE2 gained attention due to its role as a “doorway” for certain viruses to enter human cells. Coronaviruses like SARS-CoV and SARS-CoV-2 utilize ACE2 as their primary entry point. The virus’s spike protein, a structure on its surface, directly binds to the ACE2 receptor on the host cell.
This binding is similar to a key fitting into a lock, allowing the virus to initiate infection. Once the spike protein binds to ACE2, host proteases like TMPRSS2 cleave the spike protein, enabling the virus to fuse with the cell membrane and enter. In some cases, the virus can use an alternative pathway involving cathepsin L within endosomes to gain entry. This mechanism of entry through ACE2 is an important factor in how these viruses infect the body and contribute to diseases like COVID-19.
Factors Affecting ACE2
The expression and activity of ACE2 in the body can be influenced by several factors, leading to variations among individuals. Age is one such factor, with studies suggesting that ACE2 expression may differ between children and older adults, and can change as people age. For instance, older individuals may exhibit increased ACE2 expression in certain tissues like the lungs, potentially influencing disease severity.
Biological sex also plays a role, with ACE2 expression often higher in males. Underlying health conditions can further impact ACE2 levels. Patients with conditions such as diabetes, hypertension, and cardiovascular disease have shown altered ACE2 expression. For example, increased ACE2 gene expression has been observed in the heart tissue of diabetic individuals.
Certain medications, particularly those interacting with the Renin-Angiotensin System, may also influence ACE2. While some agents regulate ACE2 expression and activity, clinical studies are still exploring their effects on ACE2 levels in humans. These variations highlight why individuals may respond differently to viral infections or other physiological challenges.