Abstract
BackgroundJuvenile hormones (JH) regulate development and reproductive maturation in insects. JHs are synthesized through the mevalonate pathway (MVAP), an ancient metabolic pathway present in the three domains of life. Mevalonate kinase (MVK) is a key enzyme in the MVAP. MVK catalyzes the synthesis of phosphomevalonate (PM) by transferring the γ-phosphoryl group from ATP to the C5 hydroxyl oxygen of mevalonic acid (MA). Despite the importance of MVKs, these enzymes have been poorly characterized in insects.ResultsWe functionally characterized an Aedes aegypti MVK (AaMVK) expressed in the corpora allata (CA) of the mosquito. AaMVK displayed its activity in the presence of metal cofactors. Different nucleotides were used by AaMVK as phosphoryl donors. In the presence of Mg2+, the enzyme has higher affinity for MA than ATP. The activity of AaMVK was regulated by feedback inhibition from long-chain isoprenoids, such as geranyl diphosphate (GPP) and farnesyl diphosphate (FPP).Conclusions AaMVK exhibited efficient inhibition by GPP and FPP (Ki less than 1 μM), and none by isopentenyl pyrophosphate (IPP) and dimethyl allyl pyrophosphate (DPPM). These results suggest that GPP and FPP might act as physiological inhibitors in the synthesis of isoprenoids in the CA of mosquitoes. Changing MVK activity can alter the flux of precursors and therefore regulate juvenile hormone biosynthesis.
Highlights
Juvenile hormones (JH) play a central role in insect development and reproduction [1]
The activity of Aedes aegypti MVK (AaMVK) was regulated by feedback inhibition from long-chain isoprenoids, such as geranyl diphosphate (GPP) and farnesyl diphosphate (FPP)
AaMVK exhibited efficient inhibition by geranyl pyrophosphate (GPP) and farnesyl pyrophosphate (FPP) (Ki less than 1 μM), and none by isopentenyl pyrophosphate (IPP) and dimethyl allyl pyrophosphate (DPPM). These results suggest that GPP and FPP might act as physiological inhibitors in the synthesis of isoprenoids in the corpora allata (CA) of mosquitoes
Summary
Juvenile hormones (JH) play a central role in insect development and reproduction [1]. They are members of the “GHMP kinase family”, a group of sugar kinases that originally included galactokinases, homoserine kinases, mevalonate kinases, and phosphomevalonate kinases [8, 9] These enzymes catalyze the synthesis of phosphomevalonate (PM) by transferring the γ-phosphoryl group from ATP to the C5 hydroxyl oxygen of mevalonic acid (MA) in the presence of a divalent cation [10]. They are involved in the production of cholesterol in mammals [11], as well as JHs in insects. Despite the importance of MVKs, these enzymes have been poorly characterized in insects
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