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.

Interaction of prostaglandin E1 with human high density lipoproteins

“…The structure changes induced by PGEr appeared to be reversible: after separation of PGEr from the lipoproteins the fluorescence pol~i~tion returned almost to the initial level and after addition of a new portion of PGEr the P value increased again ( fig.3). The effect of PGEr on the fluorescence parameters of ASM-labeled HDL could be reversed also by addition of human serum albumin which effectively binds prostaglandins [8]. Interestingly, removal of PGEi from the HDL surface by addition of albumin resulted in a relatively fast decrease of E and a much slower relaxation of P (fig.4).…”

An improved LC–MS/MS method for the quantification of prostaglandins E2 and D2 production in biological fluids

“…These results indicate that this method showed excellent accuracy and precision. PGD 2 is inherently less stable in physiologic solutions than PGE 2 [30]. The instability of PGD 2 was reported in 1983 by Fitzpatrick et al [31,32] who determined that albumin catalyzes the dehydration of PGD 2 in vitro to three products.…”

Prostaglandin D2 induces programmed cell death in Trypanosoma brucei bloodstream form

“…15,17,[44][45][46] However, the active concentration of free PGs will be considerably lower, since PGs readily bind to serum albumin. [47][48][49][50] Using our conditions, 80% of PGD 2 added to the culture media was bound to serum albumin within 1 h after drug addition. Furthermore, due to the presence of albumin, PGD 2 is readily metabolized to different PGD 2 derivatives.…”