Alpha 1‐acid glycoprotein concentration and molecular heterogeneity: relationship to oxprenolol binding in serum from healthy volunteers and patients with lung carcinoma or cirrhosis.

Abstract

1. alpha 1‐acid glycoprotein (AAG) concentration and molecular heterogeneity, and oxprenolol protein binding were studied in serum of 15 healthy volunteers, 14 patients with lung carcinoma and 17 patients with liver cirrhosis. 2. The AAG serum concentration was increased to 180.7% in patients with lung cancer and decreased to 73.4% in cirrhotic patients as compared with controls (P less than 0.05). 3. The concanavalin A (conA) dependent heterogeneity of serum AAG was very similar in controls and patients with lung cancer: a ratio of 9/9/2 was obtained for the conA nonreactive, the conA weakly reactive and the conA strongly reactive subfraction respectively; in cirrhotic patients, the ratio shifted to 11/7/1. 4. The heterogeneity in electric charge, demonstrated by isoelectric focusing, was similar in the three groups of subjects: 70‐80% of the focussed bands were found in the main three bands. 5. The binding of oxprenolol to serum proteins was increased in lung tumour patients and decreased in liver cirrhotic patients as compared with controls (P less than 0.05). There was no change in binding affinity and oxprenolol binding was significantly correlated to total AAG serum concentration and to the concentration of each of the conA dependent subtypes, in controls as well as in both patients groups.

The Role of Branching Glycan of Human α1-Acid Glycoprotein in Enantioselective Binding to Basic Drugs as Studied by Capillary Electrophoresis

“…On the other hand, little is known about the effect of glycan structure. Fraeyman et al reported that oxplenolol binding to AGP is not effected by the branching glycan structure (17), but no enantioselective investigation was reported.…”

Biantennary Glycans as Well as Genetic Variants of α1-Acid Glycoprotein Control the Enantioselectivity and Binding Affinity of Oxybutynin

“…For example, the AGP concentration in normal human serum is 20Y30 mM. In cirrhotic patients, total serum AGP concentration is decreased to 73.4% of the normal concentration, and the UR/R ratio increases to 11:8 from the normal value of 9:11, although the disease does not change the heterogeneity in genetic variants (24). Our results suggest that the unbound (R)-OXY concentration in cirrhotic patients should be significantly increased.…”

“…It should be noted that the average binding affinities of (R)-OXY and (S)-OXY for the F1YS variants were similar between the UR and R fractions: Binding studies using racemic OXY would conclude that the biantennary glycan structure does not affect AGP binding, as in the case of oxprenolol (24). OXY is clinically used as a racemate.…”

“…Fraeyman et al reported that the binding of oxplenolol to AGP is not affected by the branching glycan structure (24). However, these studies did not investigate the enantioselective drugbinding ability of branching glycan in AGP variants.…”

The putative use ofα-1-acid glycoprotein as a non-invasive marker of fibrosis

“…The expression of AGP and the conformation of its oligosaccharide moiety alter in a disease-specific manner, with the concentration of AGP within plasma changing according to liver diseases, with particular differences noted when comparing primary liver diseases to cirrhosis (Arima et al, 1977;Barre et al, 1984Barre et al, , 1987Fraeyman et al, 1988). In a previous study, we also recorded differences in the glycosylation between primary liver diseases, in particular viral hepatitis, and cirrhotic samples of AGP (Anderson et al, 2002).…”