Notes Feb 1 - Feb 1 Lecture 4 Unique problem of making...

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Feb 1 Lecture 4 Unique problem of making thymine for DNA synthesis - There is a very active dUTPase that breaks dUTP to dUMP, because if the cell doesn’t have a good dUTPase, there will be some incorporateion of uracil into DNA, since the enzyme system that synthesizes DNA from dNTPs does not efficiently discriminate dUTP and dTTP - dUTP is taken into dUMP which is then methylated into dTMP - dUTP is not incorporated because of a very active dUTPase - at the diphosphate level, ribonucleotide reductase level does this methylation step - a kinase takes it to the triphosphate, and an active dUTPase brings it to the monophosphate, since kinase cannot distinguish - methyl group gets added at dUMP level- enzyme is called themidylate synthase o important target for antibacterial and cancer targets - then regular kinases bring dTMP to a higher levels - very active dUTPase must be very specific and does not take the phosphate off of dTTP - the source of the methyl group is N5,N1-THF which becomes dihydrofolate - everytime you methylate, you convert this donor molecule, which comes from folic acif, to DHF, which goes through a cycle to regenerate THF - this enzyme is one of the targets of cancer drugs
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This note was uploaded on 09/14/2011 for the course BIO 362 taught by Professor Walikarzai during the Spring '10 term at SUNY Stony Brook.

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Notes Feb 1 - Feb 1 Lecture 4 Unique problem of making...

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