Nucleic Acids (Lecture 32) Flashcards
how is uracil converted into thymine?
dTMP is synthesized from dUMP, thus dUTP must go from a triphosphate to a monophosphate
where is the methyl group derived from to synthesize thymine?
THF donates a methyl group when added to dUMP to synthesize dTMP and glutamate
the CH2 of N5,N10 methylene THF is not of the same oxidation level when compared to the CH3 of dTMP, so THF is oxidized to proved Hydrogens and is converted into DHF
how is THF regenerated and why must is gop through this step?
since the methyl group donated to form dTMP is sourced from a lower oxidation level, THF must be oxidized to DHF
regenerating THF is important to allow the enzyme to be functional again
this is done by reducing DHF via dihydrofolate reductase
what is the function of thymidylate synthase?
convert dUMP to dTMP
explain the TS cycle
- N5,N10 methylene-THF provides a methyl group to convert dUMP to dTMP via thymidylate synthase. (THF is oxidized to DHF)
- DHF is reduced via NADPH via dihydrofolate reductase to generate THF
- methylene group is added to THF via serine hydroxymethyl transferase to generate N5,N10 methylene-THF
what is the inhibitor of thymidylate synthase?
5-fluoriodeoxyuridylate (FdUMP)
This inhibits the synthesis of thymine, which is critical for DNA synthesis
what kind of inhibitor is thymidylate synthase?
suicide inhibitor : covalently modifies the enzyme
inhibitors of DHF reductase are used for…
THF analogs
competitive inhibitors used for anti cancer and antibacterial
what are some key points in the methionine cycle?
N5-methyl-THF
N5,N10-methylene-THF via thymidylate synthase
N10-formyl-THF
when there are mutations, which pathway is used to compensate and what is the treatment?
genetic mutations (i.e. inability to make pyrimidines due to orotic aciduria)
treatment is to administer enough pyrimidines to prevent the activation of the de novo pathway, thus the salvage pathway is used
what is Lesch-Nyhan disease caused by and what are the symptoms?
genetic disease caused by the loss of HGPRT activity
the symptoms are gout and mental retardation
what does nucleoside phosphorylase do?
a salvage enzyme that takes one phospho-ribose and converts it into a nucleoside
an inversion around the C1 to produce the beta configuration
what does nucleoside transglycosylase do?
takes a base and converted it directly in one step into another base
specificity to avoid making thymine ribonucleotide
salvage pathway
- 5-phosphoribose converted to PRPP via PRPP synthase
- a transferase uses PRPP to add a base and generate a nucleotide
OR
- 5-phsophoribose is converted into 1-posphoribose via mutate
- 1-posphoribose is converted to a nucleoside via a phsophorylase
- nucleoside uses kinase to become a nucleotide (puts a 5’ Pi)
how are purines degraded?
amines are removed from adenosine deaminase to form inosine from adenosine
then inosine is converted to its base, hypoxanthine and then hypoxanthine is oxidized via xanthine oxidase to form xanthine
xanthine is the. common degradation intermediate
xanthine is then oxidized again to form uric acid
