The autoactivation of factor XII in the presence of long-chain saturated fatty acids--a comparison with the potency of sulphatides and dextran sulphate.
The 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 microM-1s-1) was about 2/3 of that in the presence of sulphatide vesicles (0.053 microM-1s-1) and considerably higher than that in the presence of dextran sulphate (0.004 microM-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitropoulos
K A
KA
MRC Epidemiology and Medical Care Unit, Northwick Park Hospital, Harrow, Middlesex, UK.
Esnouf
M P
MP
D016264:Dextran Sulfate / Q000494:pharmacology*; D005174:Factor XII / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008081:Liposomes; D012709:Serum Albumin / Q000737:chemistry; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*
D005227:Fatty Acids; D008081:Liposomes; D012709:Serum Albumin; D013433:Sulfoglycosphingolipids; D005174:Factor XII; D016264:Dextran Sulfate