Lower mevalonate pyrophosphate decarboxylase activity is caused by the reduced amount of enzyme in stroke-prone spontaneously hypertensive rat.

Spontaneously hypertensive rat (stroke-prone) (SHRSP) has a low serum cholesterol level as compared with the normotensive Wistar Kyoto rat (WKY). We previously indicated that the lower activity of mevalonate pyrophosphate decarboxylase (MPD) was responsible for the reduced cholesterol biosynthesis in the liver of SHRSP [Sawamura et al. (1992) J. Biol. Chem. 267, 6051-6055]. To elucidate the mechanism of the reduced activity, we purified liver MPD from SHRSP treated with cholestyramine and pravastatin in this study. We compared its enzymatic properties with those of the enzyme from WKY, and also measured the amounts of MPD in the crude extract of various tissues in WKY and SHRSP by Western blot analysis. Results indicated that (i) MPD of SHRSP has essentially the same properties as MPD of WKY, except for a difference in the dependency on divalent cations. (ii) The amount, as well as the activity, of MPD in the crude extract of brain and liver was reduced in SHRSP. (iii) There was no difference between SHRSP and WKY, in the ratio of the enzyme activity to the amount of MPD in the crude extract. These data led us to conclude that the lower activity of MPD was caused by the reduced amount of this enzyme in SHRSP.