What Is an Aminopeptidase and What Does It Do?

Aminopeptidases are enzymes that play a significant role in the body’s biological processes by breaking down proteins and peptides. Found in various organisms from bacteria to humans, and in different cellular locations like the cytosol, membranes, and organelles, their widespread presence highlights their significance in maintaining cellular function and overall health.

Understanding Aminopeptidases

Aminopeptidases are exopeptidases that cleave amino acids from the ends of protein or peptide chains. They specifically target the N-terminus, or amino end, of these chains. This action differentiates them from carboxypeptidases, which remove amino acids from the C-terminus, and endopeptidases, which cleave peptide bonds within the middle of a protein chain. Aminopeptidases exist in both water-soluble and membrane-bound forms, found in various cellular compartments and the extracellular environment.

Mechanism of Action

Aminopeptidases break down proteins and peptides through hydrolysis. During this process, a water molecule splits the peptide bond connecting the terminal amino acid to the rest of the chain. The water molecule attacks the carbonyl carbon of the peptide bond, forming an unstable intermediate structure. The enzyme’s active site, often containing metal ions like zinc or manganese, stabilizes this intermediate and facilitates bond cleavage.

Metal ions within the active site of many aminopeptidases are important for their catalytic activity. These ions prepare the peptide bond for the water molecule’s attack, making it more susceptible to cleavage. After the peptide bond is cleaved, the terminal amino acid is released, and a shorter peptide remains, allowing the enzyme to continue its work on the newly exposed N-terminus.

Diverse Roles in the Body

Aminopeptidases are involved in various biological processes beyond simple protein breakdown. In the digestive tract, aminopeptidases like aminopeptidase N (APN) and aminopeptidase A (APA) are located on the brush border membranes of the small intestine. They play a role in the final stages of protein digestion, breaking down smaller peptides into individual amino acids for absorption by intestinal cells and nutrient utilization.

Aminopeptidases also modify hormones and neuropeptides, which are signaling molecules in the body. By cleaving specific amino acids from these peptides, aminopeptidases can activate or deactivate them, regulating their biological effects. For example, they are involved in the metabolism of opioid peptides like enkephalins, influencing their activity as neurotransmitters.

In the immune system, aminopeptidases assist in antigen processing and presentation. For instance, endoplasmic reticulum aminopeptidase (ERAAP or ERAP1) trims peptides to the correct length before presentation by MHC (Major Histocompatibility Complex) class I molecules on the cell surface. This trimming is important for the immune system to accurately recognize and respond to foreign invaders. A second aminopeptidase, ERAP2, is also present in humans and can contribute to this process.

Aminopeptidases contribute to blood pressure regulation, particularly within the renin-angiotensin system (RAS). Aminopeptidase A (APA) converts angiotensin II (AngII), a potent vasoconstrictor, into angiotensin III (AngIII), which has a similar but less potent effect. This conversion modulates the overall activity of the RAS, influencing arterial blood pressure.

Aminopeptidases and Human Health

The balanced function of aminopeptidases is important for human health, as their dysfunction can contribute to various medical conditions. For example, imbalances in aminopeptidase A (APA) activity have been observed in hypertension, where reduced APA activity in the kidneys can contribute to elevated blood pressure. Changes in maternal serum APA activity have also been noted in preeclampsia, a pregnancy complication.

Aminopeptidases are also being explored as potential therapeutic targets and diagnostic markers. Aminopeptidase N (APN), for instance, is highly expressed in new blood vessels that form during tumor growth (angiogenesis). This makes APN a target for diagnostic imaging, as NGR peptides linked to imaging probes can selectively bind to APN on tumor vasculature. Furthermore, inhibitors of aminopeptidases, such as bestatin, have been investigated for their therapeutic potential in conditions ranging from pulmonary arterial hypertension to certain cancers and viral infections where APN acts as a cell entry receptor for some coronaviruses.

Why Does My Blood Look Black? A Scientific Explanation

What Is Poor Interoception and How Can You Improve It?

Can Peptides Be Taken Orally? The Science of Absorption