title: Progressive glycosylation of albumin and its effect on the binding of homocysteine may be a key step in the pathogenesis of vascular damage in diabetes mellitus.
abstract: The majority of diabetes research to date has rightly focussed on the direct effects of hyperglycaemia on tissues and a number of theories relating to the pathogenesis of vascular disease have been proposed. This research is important as until methods are found to achieve glycaemic control in all diabetic patients, prophylactic interventions to prevent vasculopathy will be required. One of the major blood proteins, human albumin is known to be covalently modified by extended incubation with glucose, leading to an impairment of ligand binding. One of the important ligands bound by albumin is homocysteine. There is increasing and compelling clinical, experimental and epidemiological evidence that homocysteine, and in particular the free unbound fraction, is vasculotoxic. If homocysteine binding to albumin is impaired by increasing glycosylation of albumin then either drugs which reduce homocysteine levels (pyridoxine, folic acid and cobalamin) or inhibit glycosylation (aminoguanidines) may be of benefit in the prevention of vascular damage in diabetic patients.
authors.affiliation: Department of Paediatrics, Leeds General Infirmary, Clarendon Wing, Belmont Grove, Leeds, West Yorkshire LS2 9NS, England, UK. ma1hew@aol.com
authors.forename: M
authors.initials: M
authors.lastname: Mathai
authors.forename: S E
authors.initials: SE
authors.lastname: Radford
authors.forename: P
authors.initials: P
authors.lastname: Holland
mesh_terms: D000418:Albumins / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000378:metabolism*; D006031:Glycosylation; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D008955:Models, Cardiovascular; D015398:Signal Transduction
chemical_list: D000418:Albumins; D006710:Homocysteine