Serum amyloid A is often referred to in its abbreviated form; SAA. This is a group of apolipoproteins - proteins that hold together fat and cholesterol. They’re most commonly put together with HDL (high-density lipoprotein), which is found in plasma.
The majority of these proteins are produced in the liver. Research has uncovered that there might be a link between the importance of SAAs and all animal life. This is due to the fact that these proteins are conserved in all types of animals.
There are three types of serum amyloid A proteins found in rodents such as mice. These are referred to as SAA1, SAA2, and SAA3. They all follow the same genetic makeup as SAA, but each one has a slightly different mechanism and job.
SAA1 and SAA2 are primarily generated in the liver when inflammation has occurred. On the other hand, SAA3 is most likely to be generated in multiple specific tissues throughout the body. Cytokines IL-1, IL-6, and TNF-a are responsible for regulating both SAA1 and SAA2 when they’re present in liver cells. It is found that, when exposed to bacterial LPS (lipopolysaccharide) and acute inflammatory conditions are present, the amount of SAA1 and SAA2 is multiplied by 1000. This still refers to SAA proteins in mice, not humans.
However, in humans, there are also three A-SAA genes present. The only difference is that the third A-SAA gene - SAA3 - is said to be a pseudogene. These are parts of your DNA that have some relation to proper functional genes. But, they’ve not got full functionality compared to the full gene. SAA3 in humans is categorised this way due to the fact it fails to generate protein or messenger RNA.
A-SAAs are mainly secreted during the early stages of inflammation. When the body is exposed to something that causes inflammation, these proteins are induced. There are multiple functions of SAA all over the body.
The first is to help eliminate excess cholesterol in the body. When too much cholesterol is present, it gets taken to the liver, where it is secreted in bile. These proteins transport the cholesterol to the liver, for this to take place.
The second function is to bring more immune cells to inflammatory sites. When inflammation occurs, immune cells are needed to help fight against, and reduce it. Serum Amyloid A proteins recruit more immune cells, reducing the impact of inflammation on the body.
Finally, SAAs are said to the creation of enzymes that break down the extracellular matrix.
Serum Amyloid A proteins are linked to various chronic inflammatory diseases, most commonly rheumatoid arthritis.
SAA’s found in humans are made up of 122 amino acids. Furthermore, there are 18 amino acids in the cleavable signal peptide. There have been recent scientific developments that have helped discover the crystal structure of SAA.
It’s found that SAA1 has six subunits, making it a hexamer. Each unit forms a 4-helix bundle that is antiparallel with one another. The structure itself is visibly cone-shaped, and the tip of the cone is the binding site for HDL and heparin.