NUCLEOTIDES LECTURE 4 Flashcards
why is uracyl in DNA bad and how can you control it?
mimics deamination of cytosine and leads to mutations following repair/synthesis
a specific UTPase hydrolyzes dUTP to decrease its concentration and prevent its incorporation
dUTP can also come from the deamination of dCTP
uridylate kinase is not specific for ribose vs deoxyribose which can lead to production of dUDP and then dUTP
how is dUTP controlled by dUTPase?
dUTPase degrades dUTP to dUMP
dUMP is then converted to dTMP by thymidylate synthase
characteristic of thymidylate synthase
last step of synthesis of dTMP from dUMP
important target for drugs against cancer and bacteria because it is require for DNA synthesis but not for RNA synthesis
synthesis at the level of monophosphate
how does thymidylate synthase work
THF goes to DHF (dihydrofolate), oxidation reaction
methylene is reduced to methyl
which enzyme reduces DHF back to THF?
dihydrofolate reductase
what is the thymidylate synthase cycle
what does FdUMP do?
5-fluorodeoxyuridylate
suicide inhibitor
messes up thymidylate synthase
how do methotrexate, aminopterin and trimethoprim work?
inhibitors of DHF reductase
analogs of THF, mimic the substrate and bind very tightly to the enzyme
competitive inhibitor
aminopterin and methotrexate are anticancer
trimethoprim is antibacterial
how do sulfonamides (sulfa drugs) work?
where is THF used
methionine cycle and purine de novo pathway
what is the salvage pathway?
recovery of bases for making new nucleotides
more divergent and varied
what are some salvage pathway enzymes?
what does hypoxanthine/guanine phosphoribosyl transferase do and what does the loss of it lead to?
hypoxanthine+PRPP-> inosinate + PPi
guanine+PRPP-> guanylate + PPi
goes up two levels in the cube
genetic loss of HGPRT activity leads to Lesch Nyhan disease which leads to gout and mental retardation
there are other enzymes for adenine+uracil
how are nucleosides formed in the salvage pathway?
overview of the de novo pathway
purine degradation pathway
what does loss of adenosine deaminase lead to?
leads to severe combined immunodeficiency
what is gout and how is it treated?
deposition of uric acid in joints
painful, prevalent in middle aged males
thought to be due to excess meat, but more likely due to kidney disfunction
metabolic imbalance: too much purine synthesis, high PRPP levels
treated by inhibiting xanthine oxidase (the step before making uric acid)
uric acid characteristics
final degradation product of purines
the way that birds use to eliminate nitrogen
more conservation of water
purine de novo synthesis discovered by studying pigeons
uric acid is less soluble at low pH, birds lower it to precipitate the uric acid and get rid of it
naturally obtained from guano
used as fertilizer and to make gunpowder
used to make facial cream
ammonia is the cheapest energetically but it is toxic and requires water
uric acid takes lots of energy but isnt toxic and no need of water
