Multiple biochemical mechanisms behind the functions of A1M

As the body’s own antioxidant, A1M is something of a “Swiss Army knife” that can counteract the damaging effects of oxidative stress in several different ways . To achieve antioxidant defense, A1M uses one or more of the following mechanisms.

1. Reduction of molecules

A1M acts as an enzymatic reductase against a variety of target molecules (substrates)—both organic and inorganic. In this context, that means A1M can repair molecules that have been destroyed by oxidation, by adding electrons to them.

2. Capture of radicals

A1M can react with small organic radicals so that they are captured within the A1M molecule and are trapped by strong covalent bonds. The radicals, which in a free state otherwise cause oxidative stress, are thus defused, or detoxified. One example of a particle that can be captured by A1M is the highly oxidative iron-containing heme molecule, which is present in large amounts in the blood. Another example is kynurenine, a toxic breakdown product of the amino acid tryptophan.

3. Up-regulation of gene expression

A1M expression increases when cells and tissues are exposed to oxidative stress, hemoglobin and heme. This has been demonstrated in cell lines of hepatocytes and erythrocytes, in the skin, and in placental tissue. Experimental data suggest that the body’s organs are likely to be subject to dual protection from both circulating A1M molecules synthesized in the liver, and locally produced A1M molecules.

Note: Up-regulation of A1M expression has been shown in pre-eclampsia—in this case induced by hemoglobin and free radicals.

Read more

Åkerström & Gram:
A1M, an extravascular tissue cleaning and housekeeping protein (Free Radical Biology and Medicine 2014)