Mevalonate 5-pyrophosphate decarboxylase

This enzyme [EC 4.1.1.33], also known as mevalonate pyrophosphate decarboxylase, catalyzes the reaction of ATP with (i )-5-diphosphomevalonate to produce ADP, orthophosphate, carbon dioxide, and isopentenyl diphosphate. 

Shama Bhat, C. Ramasarma, T. Inhibition of rat liver mevalonate pyrophosphate decarboxylase and mevalonate phosphate kinase by phenyl and phenolic compounds. Biochem. J., 181, 143-151 (1979)... 

Mevalonate kinase and mevalonate pyrophosphate decarboxylase activities of skin fibroblasts respond in parallel to altered serum lipoprotein levels [211]. 

Not all investigators are convinced that peroxisomes are involved in cholesterol biosynthesis. In contrast to Olivier and Krisans [4], Hogenboom and colleagues have found no deficiency in cholesterol biosynthesis in fibroblasts from patients with a peroxisomal biogenesis disorder (S. Hogenboom, 2003). In addition, using a variety of biochemical and microscopic techniques, they found that mevalonate kinase, phospho-mevalonate kinase, and mevalonate pyrophosphate decarboxylase are cytosolic, not peroxisomal enzymes (S. Hogenboom, 2004). 

Bhat, C.S. and Ramasarma, T., Effect of phenyl and phenolic acids on mevalonate-5-phosphate kinase and mevalonate-5-pyrophosphate decarboxylase of the rat brain, J. Neurochem., 32, 1531, 1979. 

The conversion of mevalonate (1) to isopentenyl pyrophosphate (IPP) (4) involves two consecutive phosphorylations at position 5 by successive action of mevalonate kinase (EC 2.7.4.2) and a decarboxylation and dehydration of the tertiary alcohol group by mevalonate 5-pyrophosphate decarboxylase (EC 4.1.1.33) (Fig. 18.4) (Crotean Johnson, 1985 Gershenzon and Croteau, 1990). One mole of ATP is required for each phosphorylation reaction. Mevalonate kinase converts mevalonic acid to (5/ )-phosphomevalonate (5). The second phosphorylation is catalyzed by phospho-mevalonate kinase. The subsequent decarboxylation and dehydration is mediated by the enzyme mevalonate diphosphate decarboxylase (di- or pyrophosphomevalonate decarboxylase EC 4,1.1.3.3) this enzyme requires Mg " or Mn + and ATP for activity (Beale and MacMillan, 1988 Harrison, 1988). All three of these enzymes are found in a number of plants. 

Once mevalonate has been formed it is sequentially phosphorylated by two separate kinases yielding mevalonate 5-diphosphate. A third ATP-consuming reaction involving a decarboxylase then generates the universal isoprene unit, isopentenyl pyrophosphate (Figure 7.18). The function of the ATP in this reaction appears to be to act as an acceptor for the leaving OH group in the dehydration part of the reaction. 

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