Thymidylate synthase: Difference between revisions
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Thymidylate Synthase (TS) is an important enzyme in [[one-carbon metabolism]]. TS catalyzes the transfer of a methyl group and a hydride from 5,10-methylenetetrahydrofolate to 2-deoxyuridine-5'-monophosphate, resulting in the formation of thymidine 5'-monophosphate and dihydrofolate. This is the only de novo source of dTMP (a precursor to Thymine) in humans. <ref name="Kholodar" >DOI:10.1021/acs.biochem.1c00063</ref> | [[Thymidylate Synthase]] (TS) is an important enzyme in [[one-carbon metabolism]]. TS catalyzes the transfer of a methyl group and a hydride from 5,10-methylenetetrahydrofolate to 2-deoxyuridine-5'-monophosphate, resulting in the formation of thymidine 5'-monophosphate and dihydrofolate. This is the only de novo source of dTMP (a precursor to Thymine) in humans. <ref name="Kholodar" >DOI:10.1021/acs.biochem.1c00063</ref> | ||
2-deoxyuridine-5'-monophosphate(dUMP) + 5,10-methylenetetrahydrofolate(CH<sub>2</sub>H<sub>4</sub>F) ⇌ thymidine 5'-monophosphate(dTMP) + Dihydrofolate(H<sub>2</sub>F) | 2-deoxyuridine-5'-monophosphate(dUMP) + 5,10-methylenetetrahydrofolate(CH<sub>2</sub>H<sub>4</sub>F) ⇌ thymidine 5'-monophosphate(dTMP) + Dihydrofolate(H<sub>2</sub>F) | ||
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==Inhibition== | ==Inhibition== | ||
Methotrexate, a competitive inhibitor competes with folate substrate to bind to the active site of TS | Methotrexate, a competitive inhibitor competes with folate substrate to <scene name='49/493689/Inhibited/2'>bind to the active site</scene> of TS and inhibits the conversion of CH<sub>2</sub>H<sub>4</sub>F to H<sub>2</sub>F. This inhibition stops the conversion of products to reactants, stopping cellular reproduction. | ||
The image below shows folic acid on the top and the inhibitor methotrexate on the bottom | The image below shows folic acid on the top and the inhibitor methotrexate on the bottom. Compared the the substrate CH<sub>2</sub>H<sub>4</sub>F to H<sub>2</sub>F, methotrexate has an additional amino group, lacks four hydrogens in the ring (i.e. has more double bonds), and is N-methylated in a different position. | ||
[[Image:Methotrexate.png|400px]] | [[Image:Methotrexate.png|400px]] | ||
