title: Albumin-lipid interactions: prostaglandin stability as a probe for characterizing binding sites on vertebrate albumins.
abstract: We determined the effect of vertebrate albumins on the stability of several physiologically relevant prostaglandins. All naturally occurring prostaglandins with beta-hydroxy ketone group decomposed by first-order kinetics, dependent on the albumin concentration in 0.1 M, pH 7.4, buffer at 37 degrees C. Even subphysiological levels of albumin (1-20 mg/mL) significantly reduced the stability of these compounds in vitro. The prostaglandins with a beta-hydroxy ketone responded to albumin in the order of their intrinsic stability; namely, less stable compounds were more susceptible. The destructive effect of albumin was nearly maximal at a 1:1 mole ratio of albumin (20 mg/mL):prostaglandin (100 micrograms/mL). Albumin had no destructive effect on prostaglandins without a beta-hydroxy ketone. Albumins from different vertebrates varied in destructive severity, but all were effective. Near neutrality, in the absence of albumin, decomposition of E-type prostaglandins was practically suspended at the dehydration stage. In the presence of albumin, dehydration was accompanied by rapid isomerization reactions (e.g., PGA1 leads to PGB1) that occur only at an elevated pH. The results suggest that albumin sequesters prostaglandins to one principal binding site and exposes them to its associated highly alkaline microenvironment. This results in a uniform and predictable influence on prostaglandin stability. Our proposed model system successfully reconciles apparently anomalous or contradictory reports regarding the effect of albumin on prostaglandin stability.
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D004355:Drug Stability; D006801:Humans; D007700:Kinetics; D011453:Prostaglandins; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D012709:Serum Albumin; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D011453:Prostaglandins; D012709:Serum Albumin