Serum amyloid P component

Jump to: navigation, search

Template:Infobox gene

The serum amyloid P component (SAP) is the identical serum form of amyloid P component (AP), a 25kDa pentameric protein first identified as the pentagonal constituent of in vivo pathological deposits called "amyloid".[1] APCS is its human gene.[2]

In amyloidosis

AP makes up 14% of the dry mass of amyloid deposits[3] and is thought to be an important contributor to the pathogenesis of a related group of diseases called the Amyloidoses.[4] These conditions are characterised by the ordered aggregation of normal globular proteins and peptides into insoluble fibres which disrupt tissue architecture and are associated with cell death. AP is thought to decorate and stabilise aggregates by preventing proteolytic cleavage and hence inhibiting fibril removal via the normal protein scavenging mechanisms.[5] This association is utilised in the routine clinical diagnostic technique of SAP scintigraphy whereby radio-labelled protein is injected into patients to locate areas of amyloid deposition.[6] 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 (R-1-[6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxohexanoyl] pyrrolidine-2-carboxylic acid), a small molecule able to strip AP from deposits by reducing levels of circulating SAP.[7]

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.[8] 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 (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 (Limulus polyphemus).[9]

References

  1. Cathcart ES; Shirahama T; Cohen AS (1967). "Isolation and identification of a plasma component of amyloid". Biochim. Biophys. Acta. 147: 392–393. doi:10.1016/0005-2795(67)90420-5. 
  2. "Entrez Gene: APCS amyloid P component, serum". 
  3. Skinner M; Pepys MB; Cohen AS; Heller LM; Lian JB (1980). Freitas, Antonio Falcão de; Glenner, George G.; Costa, Pedro Pinho e., eds. Amyloid and amyloidosis: proceedings of the Third International Symposium on Amyloidosis, Póvoa de Varzim, Portugal, 23–28 September 1979. Amsterdam: Excerpta Medica. pp. 384–391. ISBN 0-444-90124-8. 
  4. Botto M, Hawkins PN, Bickerstaff MC, Herbert J, Bygrave AE, McBride A, Hutchinson WL, Tennent GA, Walport MJ, Pepys MB (August 1997). "Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene". Nature Medicine. 3 (8): 855–9. PMID 9256275. doi:10.1038/9544. 
  5. Tennent GA, Lovat LB, Pepys MB (May 1995). "Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis" (PDF). Proceedings of the National Academy of Sciences of the United States of America. 92 (10): 4299–303. PMC 41931Freely accessible. PMID 7753801. doi:10.1073/pnas.92.10.4299. 
  6. Hawkins PN, Pepys MB (July 1995). "Imaging amyloidosis with radiolabelled SAP". European Journal of Nuclear Medicine. 22 (7): 595–9. PMID 7498219. doi:10.1007/BF01254559. 
  7. Pepys MB, Herbert J, Hutchinson WL, Tennent GA, Lachmann HJ, Gallimore JR, Lovat LB, Bartfai T, Alanine A, Hertel C, Hoffmann T, Jakob-Roetne R, Norcross RD, Kemp JA, Yamamura K, Suzuki M, Taylor GW, Murray S, Thompson D, Purvis A, Kolstoe S, Wood SP, Hawkins PN (May 2002). "Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis". Nature. 417 (6886): 254–9. PMID 12015594. doi:10.1038/417254a. 
  8. Emsley J, White HE, O'Hara BP, Oliva G, Srinivasan N, Tickle IJ, Blundell TL, Pepys MB, Wood SP (January 1994). "Structure of pentameric human serum amyloid P component". Nature. 367 (6461): 338–45. PMID 8114934. doi:10.1038/367338a0. 
  9. Pepys MB, Booth DR, Hutchinson WL, Gallimore JR, Collins PM, Hohenester E (1997). "Amyloid P component. A critical review". Amyloid. 4: 274–295. doi:10.3109/13506129709003838. 

Template:PDB Gallery

Amyloidosis Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Amyloidosis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Serum amyloid P component On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Serum amyloid P component

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Serum amyloid P component

CDC on Serum amyloid P component

Serum amyloid P component in the news

Blogs on Serum amyloid P component</small>

Directions to Hospitals Treating Amyloidosis

Risk calculators and risk factors for Serum amyloid P component


Linked-in.jpg