Fludarabine inhibits DNA synthesis by interfering with ribonucleotide reductase and DNA polymerase. This reaction is catalyzed by the enzyme glutathione reductase. This conversion involves the enzyme ribonucleoside triphosphate reductase. The enzyme ribonucleotide reductase (RNR) catalyzes the de novo synthesis of dNDPs. Statins act by inhibiting the enzyme hydroxymethylglutaryl CoA reductase (HMG-CoA-reductase) in the liver. AMPK also phosphorylates and inactivates 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a key enzyme in cholesterol synthesis. Methotrexate inhibits dihydrofolate reductase (DHFR), an enzyme that regenerates tetrahydrofolate from dihydrofolate. This molecule is then reduced to mevalonate by the enzyme HMG-CoA reductase. The mechanism involves a tyrosine residue in the active site of aldehyde reductase. The iron-containing proteins ribonucleotide reductase and aconitase are deactivated by NO. Its active metabolite, cycloguanil, is an inhibitor of dihydrofolate reductase (DHFR). This conversion is catalysed by ribonucleotide reductase (see figure). Mutations in the malarial gene for dihydrofolate reductase may reduce its effectiveness. The ferredoxin reductase is such an example. Then, the NAD(P)H dependent enzyme dihydropteridine reductase (DHPR) converts q-BH back to BH.