title: Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure.
abstract: Human serum amyloid P component (SAP) is a normal plasma protein and the precursor of amyloid P component (AP), a universal constituent of the abnormal tissue deposits in amyloidosis, including Alzheimer disease. We show here that its single N-linked biantennary oligosaccharide does not display the microheterogeneity usually characteristic of glycoproteins. The protein and the glycan structures of AP were also invariant, their resistance to degradation suggesting a role in persistence of amyloid deposits. Asialo-SAP was rapidly cleared from the circulation in mice by a mechanism dependent on terminal galactose residues and was catabolized in hepatocytes. However blockade of this pathway did not affect the clearance of native SAP. Rapid hepatic uptake and catabolism of human asialo-SAP in man were also directly demonstrated. The protein and glycan homogeneity of SAP and the integrity of AP suggest that the complete glycoprotein structure is important for the normal and the pathophysiological functions of this molecule.
authors.affiliation: Immunological Medicine Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
authors.forename: M B
authors.initials: MB
authors.lastname: Pepys
authors.forename: T W
authors.initials: TW
authors.lastname: Rademacher
authors.forename: S
authors.initials: S
authors.lastname: Amatayakul-Chantler
authors.forename: P
authors.initials: P
authors.lastname: Williams
authors.forename: G E
authors.initials: GE
authors.lastname: Noble
authors.forename: W L
authors.initials: WL
authors.lastname: Hutchinson
authors.forename: P N
authors.initials: PN
authors.lastname: Hawkins
authors.forename: S R
authors.initials: SR
authors.lastname: Nelson
authors.forename: J R
authors.initials: JR
authors.lastname: Gallimore
authors.forename: J
authors.initials: J
authors.lastname: Herbert
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D001212:Asialoglycoproteins / Q000378:metabolism; D002240:Carbohydrate Sequence; D005260:Female; D006801:Humans; D008657:Metabolic Clearance Rate; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D000683:Serum Amyloid P-Component / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000682:Amyloid; D001212:Asialoglycoproteins; D000683:Serum Amyloid P-Component