Determination of mevalonate in blood plasma in man and rat. Mevalonate "tolerance" tests in man.

Abstract

A method is described for the determination of mevalonate in ultrafiltrates of blood plasma. The method depends on the phosphorylation of mevalonate with [gamma-32P]ATP and mevalonate kinase to 5-[32P]phosphomevalonate, and the subsequent isolation of the 5-[32P]phosphomevalonate together with known amounts of added 5-phospho[14C]mevalonate by ion-exchange chromatography. The 32P/14C ratio in the isolated 5-phosphomevalonate is a linear function of the mevalonate content of the samples. The smallest amount that can be determined is 1--2 pmol. The fasting level in human plasma varied between 20 and 75 pmol/ml. Human red blood cells absorb mevalonate from plasma relatively slowly; their maximum storage capacity is about 1.3 pmol/10(6) red cells. An oral and intravenous "mevalonate tolerance test" in man is described that can be carried out with 200 and 30 mumol. respectively, of the unlabeled (RS)-mevalonate in a 70-kg man. Beer and wine contain mevalonate at a concentration of 3--8 microns, too low to provide a significant amount of mevalonate even for heavy drinkers. The mevalonate content of the plasma from the blood of the vena cava inferior of male rats varied between 81 and 502 pmol/ml and is positively related to the levels of liver 3-hydroxy-3-methylgultaryl-CoA reductase, suggesting that the liver is probably the main source of mevalonate circulating in blood. The plasma of renal venous blood contained only 33--85% as much mevalonate as the arterial plasma.