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Lecture 32- Folate SUMMARY

Lecture 32- Folate SUMMARY - /fi Nucleotide Felicficid...

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Unformatted text preview: /fi Nucleotide . . Felicficid BlosyntheSIS l, J, DHFR scrim TetrahydmfolatefiHF} Methianinea S-adenasylmefihianine Dimemflghfline K wfil BHMT - uridvlate “”3 #5 ifl-CHz-THF —- 5-CHa-THF HomowsteineeS—adenesvlhomowstteine MTHFR 4 Thymidylate i a £035 iU-CHO-THF Wei“? /— purines Cellular / Methyiation NA \\ __ D mfgw RN35; a k:“ Methotrexate is an anti—folate drug used to treat cancer “mm” Works by binding to dihydrofolate reductase [DHFR) in lieu of folic acid Tumor-promoting mechanism: l. DNA strand breaks Tumor - Inhililtorg-r mechanisms: l. Ineffective DNA synthesis loading to inhibition of tumor growth and progression 2. Reversal of promoter CpG islands 2. Impaired DNA repair 3. Increased mntagenesis 4. Genomic DNA hypomethyiation Folflte —3ficienc3 hypem'iethylation'? progression of progression of progression of ' early IEN late IEN to cancer cancer Premalignant transformation and abnormal growth Normal — Intraepithelial Neoplasia—r Cancer risk of neoplastic progression of progression of progression of transformation earl-y [EN late IEH to cancer cancer Folate _upplementatian risk of neoplastic tramrormatlon Tumor~inhihimry mechanisms: 1. DNA stability and integrity Tmnar-promating mechan'ems: L Provision of nucleotide precursors. for proliferation and growth of neoplastic cells 2. Optimal DNA repair 3. Decreased mutagenesis 4. Prevention of aberrant DNA methylation 2. De novo methylation of promoter Cpfi islands of tumor suppressor genes leading to gene inactivation 3. Hypen'n utabt'lity of methylated cytosines in {3:36 ...
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