Pyrophosphomevalonic acid

Tada, M., and Lynen, F. (1961). On the biosynthesis of terpenes. XIV. On the determination of phosphomevalonic acid kinase and pyrophosphomevalonic acid decarboxylase in cell extracts. J Biochem 49 758-764. 

Henning, V., E. M. Moslein, and F. Lynen Biosynthesis of terpenes V. Formation of 5-pyrophosphomevalonic acid by phosphomevalonic kinase. Arch. Biochem. 83, 259(1959). 

Cell-free extracts and acetone powder preparations from Agave amerkana have been shown to phosphorylate mevalonic acid to give phosphomevalonic acid and thence pyrophosphomevalonic acid at an optimum pH of 7.0. Glutathione and mercaptoethanol enhance the activity of these preparations. Tracer studies with tissue cultures derived from Tanacetum vulgare have revealed the formation of phosphomevalonic acid, pyrophosphomevalonic acid, isopentenyl pyrophosphate, dimethylallyl pyrophosphate, and the incorporation of mevalonic acid into monoterpenes. However, the mono-terpene components of the tissue culture differed from those of the whole plant, sabinene being formed rather than isothujone. 

Mevalonic acid is converted to 5-pyrophosphomevalonate in two steps, each of which transfers a phosphate group from ATP. 

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. 

As soon as mevalonate acid has formed, a series of enzymes are involved in order to transform MVA to IPP. Mevalonate kinase [EC 2.7.1.36] phosphorylates the primary alcohol to mevalonate 5-phosphate, whereas phosphomevalonate kinase [EC 2.7.4.2] produces 5-pyrophosphomevalonate... 

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