The Autoactivation of Factor XII in the Presence of Long-Chain Saturated Fatty Acids – A Comparison with the Potency of Sulphatides and Dextran Sulphate

Abstract

SummaryThe incubation of purified human factor XII (Hageman factor [HF]) in the presence of long-chain saturated fatty acids (FA) like stearate (C-18) or behenate (C-22) resulted in a time-dependent increase of amidolytic activity. The HF autoactivation progress curves were sigmoidal. The first order rate for the initial period was constant; this was followed by a period of decreasing rate and a plateau of zero rate. These progress curves were similar to those obtained on the incubation of HF in the presence of sulphatide vesicles or dextran sulphate. The initial rate of autoactivation of HF was dependent on the FA concentration of contact surface and increased with increasing concentration of HF. At constant concentration of contact surface and varying concentration of HF, autoactivation rates in the presence of behenate, sulphatide vesicles or dextran sulphate followed Michaelis-Menten kinetics. The Km values for all three contact surfaces were above the physiological plasma concentration of HF whereas the catalytic efficiency in the presence of behenate (0.034 εM-1s-1) was about % of that in the presence of sulphatide vesicles (0.053 εM-1s-1) and considerably higher than that in the presence of dextran sulphate (0.004 εM-1s-1). Long-chain saturated FA bound to human serum albumin at the high- or low-affinity sites are ineffective, whereas the crystalline non-bound stearate or behenate provided a potent contact surface. Since oleic acid or other unsaturated fatty acids did not promote autoactivation it is suggested that the requirement for an effective contact surface is one containing immobile negatively charged groups with a critical charge density such as that found in miscelles composed of FA in the crystalline phase. It is suggested that saturated FA on triglyceride-rich lipoproteins resulting from the action of lipoprotein lipase could provide these requirements.