Mevalonate. decarboxylation isopentenyl diphosphate from

Methyl-l-propanol, l3C NMR spectrum of. 453 2-Methylpropene, heat of hydrogenation of. 187 Mevalonate, decarboxylation of, 1075 isopentenyl diphosphate from, 1072-1075... 

In animals all isoprenoid compounds are apparently synthesized from mevalonate, which is converted by the consecutive action of two kinases21 23 into mevalonate 5-diphosphate (Fig. 22-1, step b). Mevalonate kinase is found predominantly in peroxisomes, which are also active in other aspects of steroid synthesis in humans.2124 A deficiency of this enzyme is associated with mevalonic aciduria, a serious hereditary disease in which both blood and urine contain very high concentrations of mevalonate.23 Mevalonate diphosphate kinase, which is also a decarboxylase, catalyzes phosphorylation of the 3-OH group of mevalonate (step c, Fig. 22-1) and decarboxylative elimination of phosphate (step d)25 to form isopentenyl diphosphate. 

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. 

Scheme 11.41. The enzyme-catalyzed phosphorylation (ATP -y ADP) and decarboxylation (with elimination of inorganic phosphate) of (i )-mevalonate [(i )-3,5-dihydroxy-3-methylpentanoic acid] to isopentenyl diphosphate (diphosphoric acid mono-[3-methylbut-3-enyl] ester) and the isomerization of the latter to dimethylallyl diphosphate (EC 5.3.3.2). It is important to note that the isomerization involves the specific removal of the pro-R hydrogen of C2 of the former. EC numbers and some graphic materials provided in this scheme have been taken with permission from appropriate links in a URL starting with http // www.chem.qmul.ac.uk/iubmb/enzyme/.

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