Stable Copper Isotope Incorporation Into Serum Caeruloplasmin in Human Health and Disease

Fletcher, Alexander (1995) Stable Copper Isotope Incorporation Into Serum Caeruloplasmin in Human Health and Disease. ["eprint_fieldopt_thesis_type_MMedSc" not defined] thesis, University of Glasgow.

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Abstract

Wilson's disease (WD) is a treatable inborn error of metabolism inherited in an autosomal recessive fashion (world-wide incidence 1:200,000). WD is a type of copper toxicity in which copper accumulation results from failure of normal liver transport into bile. The identification of affected individuals within a known family is important to prevent irreversible neurological and/or hepatic damage. The determination of serum and urine copper and of serum caeruloplasmin concentrations are usually but not always sufficient to make a diagnosis. A dynamic test to assay the incorporation of labelled Cu into serum caeruloplasmin may help diagnosis in equivocal cases. Tracer studies utilising the stable isotope 65Cu offers numerous practical advantages over the expensive and short-lived 64Cu (12hrs) and 67Cu (72hrs) radio-isotopes. A method for the determination of 65Cu in serum has been established using inductively coupled plasma mass spectrometry (ICP-MS). The pattern of 65Cu incorporation into the plasma protein pool of normals, heterozygotes for the WD gene and cases at timed intervals after oral dosage has now been documented. Can these measurements be improved by isolation from plasma of the main plasma Cu containing protein, caeruloplasmin? Fast protein liquid chromatography (FPLC; Pharmacia) was employed to separate the main 65Cu containing plasma protein caeruloplasmin. Albumin was separated by gel filtration and affinity chromatography to varying degrees, subsequent advances in affinity media for Cp gave superior results. Initially, four normal volunteers were given 65Cu orally, and had blood samples withdrawn at intervals up to one month. The fresh serum was prepared for ICP-MS analysis of total 65Cu and caeruloplasmin bound copper isolated. This thesis describes the development of methods to isolate the copper containing plasma protein caeruloplasmin labelled in vivo with 65Cu.

Item Type: Thesis (["eprint_fieldopt_thesis_type_MMedSc" not defined])
Qualification Level: Masters
Additional Information: Adviser: G S Fell
Keywords: Biochemistry, Toxicology
Date of Award: 1995
Depositing User: Enlighten Team
Unique ID: glathesis:1995-76319
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 15:46
Last Modified: 19 Nov 2019 15:46
URI: http://theses.gla.ac.uk/id/eprint/76319

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