INFLUENCE OF HYPOXANTHINE AND OTHER PURINES ON THE LECITHIN - CHOLESTEROL ACYLTRANSFERASE REACTION IN THE PLASMA OF RAT AND OTHER SPECIES

1. Esterification of radiolabelled cholesterol in the plasma of rat, mouse, pig, ox and, to a lesser extent, guinea pig was partially inhibited by hypoxanthine, xanthine and guanine; esterification in human plasma and in plasma from 12 other vertebrate species was unaffected by purines. 2. Esterification of endogenous cholesterol and the formation of lysolecithin in rat plasma were decreased in the presence of purines indicating that it was the lecithin:cholesterol acyltransferase (LCAT) reaction that was inhibited rather than the isotopic equilibration of labelled cholesterol with the endogenous substrate lipoproteins. 3. Maximum inhibition of the LCAT reaction in rat plasma occurred at 1.4 mM hypoxanthine or xanthine; inhibition was not dependent upon the concentration of LCAT or plasma lipoproteins but increased with the amount of lipoprotein depleted rat plasma (LDRP) present in the incubation mixture. 4. Partial inhibition of the LCAT reaction in rat or mouse plasma by purines had no significant effect on the fatty acyl composition of the cholesteryl esters (CE) formed by LCAT. 5. In the presence of heated rat plasma, LDRP or, to a lesser extent, rat high density lipoproteins (HDL) prepared from heated plasma, the LCAT reaction in human plasma was inhibited by hypoxanthine. 6. Rat HDL and LDRP prepared from plasma pre-incubated at 37-degrees-C for 4 hr before heating increased and decreased, respectively, the inhibitory effect of hypoxanthine on human plasma LCAT compared with HDL and LDRP prepared from unincubated rat plasma. 7. These findings suggest that purines inhibit the LCAT reaction in rat plasma not through any direct effect on the enzyme, but by interacting with a protein present both in HDL and in LDRP; this protein may be an apolipoprotein co-factor of LCAT not found in human plasma.