Phospho-5-pyrophosphomevalonate

In the next stage of cholesterol synthesis, three phosphate groups are transferred from three ATP molecules to mevalonate (Fig. 21-35). The phosphate attached to the C-3 hydroxyl group of mevalonate in the intermediate 3-phospho-5-pyrophosphomevalonate is a good... 

FIGURE 21-35 Conversion of mevalonate to activated isoprene units. Six of these activated units combine to form squalene (see Fig. 21-36). The leaving groups of 3-phospho-5-pyrophosphomevalonate are shaded pink. The bracketed intermediate is hypothetical. 

IPP) is the other. IPP is synthesized from 3-phospho-5-pyrophosphomevalonate, as shown in Figure 19.19. The first step in isoprenoid synthesis is as follows ... 

In a series of cytoplasmic reactions, mevalonate is subsequently converted to famesylpyrophosphate. Mevalonate kinase catalyzes the synthesis of phospho-mevalonate. A second phosphorylation reaction catalyzed by phosphomevalonate kinase produces 5-pyrophosphomevalonate. 

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. 

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