Key result
The addition of oleate or palmitate in amounts up to a 2:1 molar excess to human serum albumin increased the rate constant for the transition of warfarin binding compared to fatty acid-free albumin.
Why the study?
Does the addition of palmitate or oleate alter the binding kinetics of warfarin to human serum albumin in vitro?
Does the addition of palmitate or oleate alter the binding kinetics of warfarin to human serum albumin in vitro?
Elevated fatty acid levels allosterically modulate warfarin binding to human serum albumin, suggesting that prolonged high fatty acid levels could reduce plasma protein binding of coumarins and potentially enhance their pharmacological activity.
Fatty acid elevation may enhance warfarin activity via reduced albumin binding; leaves open clinical translation from this in vitro model.
The rate of transition from an unstable to a stable complex and the dependence of this on the number of fatty acid ligands present was determined for the binding of warfarin on human serum albumin. When oleate or palmitate was added in amounts up to 2:1 excess to human serum albumin solutions the measured rate constant for the transition (k2) was increased in comparison with fatty acid free albumin. When the fatty acid concentration is further increased, k2 decreases. When the fatty acid level is 2 to 3 mol per mol albumin, the affinity constant (KA) is higher than for fatty acid free solutions. With higher ratios the value for KA is reduced. According to the observed changes in kinetic parameters, the binding of warfarin is apparently affected allosterically. A reduced plasma protein binding of coumarins should be expected when fatty acid levels are raised over a prolonged period.
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Rietbrock et al. (1985) studied this question. Palmitate and Oleate vs. Fatty acid-free human serum albumin was evaluated on Rate of transition from unstable to stable complex (k2) and affinity constant (KA). The addition of oleate or palmitate in amounts up to a 2:1 molar excess to human serum albumin increased the rate constant for the transition of warfarin binding compared to fatty acid-free albumin.
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