Phosphomevalonate kinase EC

The next reaction in the transformations of mevalonate is unusual in that the transfer of a phosphoryl entity from ATP to mevalonate-5-phosphate forms the 

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Full details have appeared of the rubber enzyme phosphomevalonate kinase (EC 2.7.4.2) and 5-pyrophosphomevalonate decarboxylase (EC 4.1.1.33). 

Then (Scheme 11.41) mevalonate [(l )-3,5-dihydroxy-3-methylpentanoic acid] is phosphorylated by the enzyme mevalonate kinase (EC 2.7.1.36) at the primary hydroxyl. The phosphate that is added is obtained (an addition-elimination reaction or a displacement reaction) from the terminal phosphate group of ATP forming ADP in turn. Another phosphorylation, again using ATP yields mevalonate diphosphate, this time by the enzyme phosphomevalonate kinase (EC 2.7.4.2) and then, after one more phosphorylation, this time on the tertiary hydroxyl, decarboxylation and dehydration co-occur, catalyzed by the enzyme mevalonate diphosphate decarboxylase (EC 4.1.1.43). The products are inorganic phosphate, carbon dioxide, and isopentenyl diphosphate (diphosphoric acid mono[3-methylbut-3-enyl] ester). Isopentenyl diphosphate isomerase (EC S.3.3.2) catalyzes the isomerization, via loss of the C2 pro-R hydrogen, between isopentenyl diphosphate and dimethylallyl diphosphate. 

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... 

Phosphomevalonate kinase (PMK, EC 2.7.4.2) is the enzyme involved in the second step of the terpenoid biosynthesis and catalyzes the reversible conversion of mevalonate 5-phosphate and ATP to mevalonate 5-diphosphate and ADP, a key step in that synthesis. Fig. (6), [289-290]. Kinetic characterisation of PMK has been carried out using enzymes from mainly animal sources including human, S. cerevisiae and some plants. In addition, PMK has only been partially purified and characterized. It seems that this enzyme is quite a unique enzyme, but its characteristics reveal some remarkable differences among diverse sources. Thus, pig liver and human liver PMKs show molecular weights between 21 and 22 kDa [291-292], whereas the enzyme isolate from S. cerevisiae has a molecular weight of 47 kDa [293]. 

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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