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36 Cards in this Set
- Front
- Back
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How are diP formed?
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BASE specific kinases (non-specific for deoxy/ribose)
monoP-> diP adenylte kinase: (d)AMP + ATP <=> (d)ADP + ADP uridylate kinas: (d)UMP + ATP<=> (d)UDP + ADP |
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How are triP formed?
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Via ubiquitous non-specific kinase
Nucleoside diP kinase: (d)NDP + (d)N'TP <=> (d)NTP + (d)N'DP both formation of di and tri P run close t equilib (G=0) |
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How does the ration of ADP/AMP compare to ATP/ADP?
NTP/NDP to N'TP/N'DP? |
They're about the same for bothe cases
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What do cells have more of: DNA or RNA?
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RNA (have ribosomes etc)
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What is the difference btw ADP and ATP? AMP? Btw GDP and GTP?
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10X more ATP then ADP, even less AMP
7fold dif btw GDP and GTP |
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What are the intracellular amounts of nucleotides and PRPP in cells? (ratios)
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~7x more RNA than DNA
~7x more NTP than dNTP ~7x more NTP than NDP ~7x more NDP than NMP .: ~50x more NTP then NMP |
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What determines the relative conc of nuceotides in the cell?
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Energy charge (i.e [ATP]/[ADP])
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Which is more reduced, DNA or RNA?
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DNA
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At what lvl are deoxyribose?
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carried out at lvl of DNPs (diP)
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Why doesn't DNA have a 2' OH?
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RNA is less stable and hydrolyzes under alkaline conditions (nuc attack by 2'OH on PO4, get a 2',3' cyclic P--> can end up in RNA)
End up cleaving your backbone and hydrolyzing the RNA .: avoid this by getting rid of your 2'OH and making DNA |
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What does ribonucleotide reductase (RR)?
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Makes DNA nucleotide from RNA (loss of O in 2' position)
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What is used as reducing power? What is used as oxidizing power?
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Red: NADPH
Oxid: NAD+ |
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Why is NADPH used to reduce RNA to DNA?
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More NADPH then NADH, NADPH conc will run downhill
-NADPH coupled through thioredoxin to actual enzyme -> RR (thioredoxin has thiols from cys res) |
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How many allosteric sites does RR (ribonucleotide reductase) have? How is RR regulated?
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2
-activity controlled by ATP/dATP levels =>high lvls of ATP, enz more active cuz this enz req'd to keep the~7fold dif btw lvls of ATP and dATP => too much dATP, reduce activity of RR, fdbk inhibition -Specificity controlled by dATP/dGTP/dTTP |
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What are the 2 lvls of regulation of RR?
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Activity (ATP, dATP)
Specificity (dATP, dGTP, dTTP) |
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What are characteristics of the tyrosine free radical in RR?
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unusually stable
->Inhibited by hydroxyurea -> peptidomimetics against viral RR's |
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What does hydroxyurea do?
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Inhibitor of RR
destroys tyr free radical blocks activity of the enz |
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How many types of fdbk regulation maintain proer and equilibrated lvls of dNTP's for DNA synthesis?
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2 (activity and specificity)
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What level are deoxyribonuc made at?
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NDP lvl (diP)
(ADP, GDP) |
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Where does RR work in the pyrimidine path?
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look for XDP-->dXDP
CDP-->dCDP UDP-->dUDP (but not suppose to have U in DNA) |
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Why is it bad to incorporate Uridine into DNA?
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Mimincs deamindation of cytosine and leads to mutations following repair/synthesis
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How is incorporation of U into DNA prevented?
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Specific enz UTPase hydrolyzes dUTP to dec its concentration and prevent its incorporation
->hydrolyzes 2 P from dUTP, release PPi and make dUMP |
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What's the dif btw U and T?
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U with a methyl gp = T
(don't want to confuse U with natural deamination of C-> U, .: only add T in DNA) When cell sees a U in DNA, turns it into a C cuz it thinks it came from cytosine |
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What is important about the synthesis of thymidylate step?
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make dTMP from dUMP
works at level of monoP Important target against cancer and bacteria required for DNA but not RNA synthesis Enz= Thymidylate sunthetase |
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How is thymine synthesized?
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At the lvl of deoxyribose monoP (made from dUMP)
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Where does most dUMP come from?
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action of dUTPase on dUTP
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What rxn does thymidylate synthetase catalyze?
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dUMP + N5, N10-Methylene-THF --> dTMP + DHF
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What is the dif btw DHF and THF?
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DHF is more oxidized than THF, has a db and one less H
Oxid of THF-->DHF gives E for reducton of methylene to methyl |
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What is the TS cycle?
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THF oxidized to DHF
DHF reduced by DHF reductase Add methylene group from serine |
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Why does THF have to be regenerated?
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Won't be able to make any more thymine without THF
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In what processes is the syn of thymidine a critical step?
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Syn of DNA
Treatment of cancers Treatment of viral an bacterial infections |
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What does FdUMP do?
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Inhibits dUMP --> dTMP step
Its a suicide inhibitor When cells incorporate this into nuc, form covalent adducts w/ thymidylate synthase -suicide inhibitor cuz every molec ends up bound by it (lose inhib but remove enz) |
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What enz reduces DHF to THF?
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dihydrofolate (DHF) reductase
(When DHF is reduced, NADPH is oxidized to NADP+) |
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What are inhibitors of DHF reductase? (DHF--> THF)
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Aminopterin: anti-cancer
Methotrexate: anti-cancer Trimethoprim:antibacterial --> they are all THF analogs -->Competitive inhibitors |
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What do sulfamides do?
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Structural analogues of the p-aminobenzoic acid constituent of THF
--> block de novo synthesis of THF in bacteria -->Animals get THF from diet so they are insensitive to sulfamides, .: can use it to fight bact infections (urinary tract) |
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What is THF required for?
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Thymine synthesis
-->N5,N10-methylene THF Purine de novo -->N10-formyl-THF |
