The serum amyloid P component (SAP) is the identical serum form of amyloid P component (AP), a 25kDa

pentameric protein A pentameric protein is a quaternary protein structure that consists of five protein subunits. Examples Ligand-gated ion channels Five sub-units come together to form a channel. Each channel consist of two alpha chain, one beta, one gamma and o ...

first identified as the pentagonal constituent of in vivo pathological deposits called "

amyloid Amyloids are aggregates of proteins characterised by a Fibril, fibrillar morphology of 7–13 Nanometer, nm in diameter, a beta sheet (β-sheet) Secondary structure of proteins, secondary structure (known as cross-β) and ability to be Staining, ...

". APCS is its human

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

In amyloidosis

AP makes up 14% of the dry mass of amyloid deposits and is thought to be an important contributor to the pathogenesis of a related group of diseases called the Amyloidoses. These conditions are characterised by the ordered aggregation of normal globular proteins and

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

s into insoluble fibres which disrupt tissue architecture and are associated with cell death. AP is thought to decorate and stabilise aggregates by preventing

proteolytic Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...

cleavage and hence inhibiting fibril removal via the normal

protein scavenging mechanisms Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respond ...

. This association is utilised in the routine clinical diagnostic technique of

SAP scintigraphy A SAP scan is a type of nuclear medicine imaging test which uses iodine-123 (123I) and serum amyloid P component (SAP) to diagnose amyloidosis. In patients with amyloidosis, large deposits of SAP coat the affected organs, in addition to the low ...

whereby radio-labelled protein is injected into patients to locate areas of amyloid deposition. The SAP-amyloid association has also been identified as a possible drug target for anti-amyloid therapy, with the recent development and first stage clinical trials of a compound called

CPHPC CPHPC ((''R'')-1-pyrrolidine-2-carboxylic acid) is a proline-derived small molecule able to strip amyloid P (AP) from deposits by reducing levels of circulating serum amyloid P (SAP). The SAP-amyloid association has also been identified as a poss ...

(R-1- -[R-2-carboxy-pyrrolidin-1-yl6-oxohexanoyl.html" ;"title="-2-carboxy-pyrrolidin-1-yl.html" ;"title="-[R-2-carboxy-pyrrolidin-1-yl">-[R-2-carboxy-pyrrolidin-1-yl6-oxohexanoyl">-2-carboxy-pyrrolidin-1-yl.html" ;"title="-[R-2-carboxy-pyrrolidin-1-yl">-[R-2-carboxy-pyrrolidin-1-yl6-oxohexanoylpyrrolidine-2-carboxylic acid), a small molecule able to strip AP from deposits by reducing levels of circulating SAP.

Structure

SAP is a member of the pentraxins family, characterised by calcium dependent ligand binding and distinctive flattened β-jellyroll structure similar to that of the legume lectins. The name "pentraxin" is derived from the Greek word for five (penta) and berries (ragos) relating to the radial symmetry of five monomers forming a ring approximately 95 Å across and 35 Å deep. Human SAP has 51% sequence homology with

C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin-6 ...

(CRP), a classical acute phase response plasma protein, and is a more distant relative to the "long" pentraxins such as PTX3 (a cytokine modulated molecule) and several neuronal pentraxins. Both SAP and CRP are evolutionary conserved in all vertebrates and also found in distant invertebrates such as the

horseshoe crab Horseshoe crabs are marine and brackish water arthropods of the family Limulidae and the only living members of the order Xiphosura. Despite their name, they are not true crabs or crustaceans: they are chelicerates, most closely related to arachn ...

(Limulus polyphemus).

References

{{Amyloidosis Blood proteins Acute-phase proteins