nucleotide metabolism 2 Flashcards
all nucleoside X-phosphates are ____
dNXP means ____ is sugar, NXP means ____ is sugar
nucleotides
deoxyribose, ribose
DNA nucleotides are dervied from
RNA nucleotides
important precursor for all nucleotides is
PRPP
de novo synthesis of ribonucleotides - pyrmidines:
- forms nitrogenous base:
- ____ pathway
- occurs in ____
- precursors used
- ____ from ____
- ____
- ____
- allosteric regulation
- ____ inhibits (C)
- ____ activates (A/G)
- independent of PRPP
- unidirectional
- cytoplasm
- NH3 from Gln
- Asp
- HCO3-
- NH3 from Gln
- pymidine
- purine
- pymidine
de novo synthesis of ribonucleotides - purines:
- form nitrogensous base:
- ____ pathway
- occurs in ____
- precursers used
- ____ from ____
- ____
- ____
- ____
- ____
- regulation: feedback inhibtion b ____
- on PRPP
- branched
- cytoplasm
- NH3 from Gln
- Gly
- Asp
- N10 - formyl-THF
- HCO3-
- NH3 from Gln
- purines
carbamoyl phosphate synthetase II (CPSII):
- used in ____ synthesis
- part of ____ complex
- bicarbonate → ____ → ____ → ____
- NH3 (from glutamine) → ____ → ____
- activators:
- inhibitors:
- pyrimidine
- CAD
- carboxyphosphate → carbamic acid → carbamoyl phosphate
- PRPP and ATP
- UTP
de novo synthesis of ribonucleotides - pyrimidines steps:
- CAD
- CPSII
- Aspartate transcarboamobylase (ATCase)
- (1) activates:
- (2) inhibits:
- Dihydroorotase
- (3) closes the ____
- dihydroorotate dehydrogenase
- (4) located in ____
- UMP Synthetase
- (5) removes PPi when ____ is added to PRPP
- (6) decarboxylates orotate to form ____
- nucleoside monophosphate kinases are ____ to each NMP
- (7) e.g. UMP + ATP → ____ + UDP
- nucleoside diphosphate kinase has ____ specificity
- CTP synthetase
- (8) UTP → ____
- (9) **CTP is the only nucleotide to be synthesized directly as a ____
- (1) ATP
- (2) CTP
- (1) ATP
- (3) ring
- (4) mitochondria
- (5) orotate
- (6) uracil
- (5) orotate
- specific
- (7) UDP
- broad
- (8) CTP
- (9) triphosphate
- (8) CTP
de novo synthesis of ribonucleotides - purines:
- reactions 1-3 forms the 5 membered ring
- swaps PPi of PRPP for NH3 from ____
- adds ____
- adds a formyl group from ____ to complete the ring
- reactions 4-10 form the 6 membered ring
- adds an NH3 from ____ to start the second ring
- closes the ____-membered ring
- adds CO2 from ____, first to Gln then to Gly
- adds ____ at the carboxyl
- releases ____
- second addition on a formyl group from another ____ completing the 6 membered ring
- closes the 6 membered ring forming ____
- Gln
- Glycine
- THR
- Gln
- 5
- HCO3-
- CO2
- Asp
- fumarate
- THF
- hypoxanthine
in vertebrates, purines are made in the
purinosome
branch point for purine synthesis
inosine monophosphate (IMP)
purines - branching from IMP:
- AMP
- uses ____ for energy
- replaces carbonyl with ____ from ____
- releases ____
- inhibited by ____
- GMP
- uses ____ for energy
- redox with H2O to make 2nd carbonyl, then replaces it with ____ from ____
- inhibited by ____
- AMP
- GTP
- NH3 from Asp
- fumarate
- AMP
- GMP
- ATP
- NH3 from Gln
- GMP
in both pyrimidine and purine synthesis, nucleoside monophosphate kinases are ____ to each NMP
in both pyrimidine and purine synthesis, nucleoside diphosphate kinase has ____ specificity
specific
broad
hereditary orotic aciduria:
- caused by deficiency of ____ ____
- excessive ____ excreted the urine
- megaloblastic anemia that fails to respond to ____ treatment
- megaloblastic anemia occurs when cells fail to ____
- UMP synthetase
- orotate
- B9/B12
- divide
UMP synthetase removes PPi when ____ is added to ____ and decarboxylates orotate to form ____
orotate
PRPP
uracil
deoxyribonucleotide synthesis overview:
converting ribose to deoxyribose requires a ____ reaction
deoxyribonucleotides are created from their respective ____
pyrimidines take a ____
reduction
NDPs
detour
ribonucleotide reductase:
- function:
- ____ reaction
- catalytic ____ is a free radical
- not picky, so it acts on all ____ and ____
- ____ provides the necessary electrons from redox reactions
- regulation
- active site = ____ site
- allosteric site
- activity site and acts as a ____ switch
- ____ promotes function
- ____ turns off
- specificity site and acts as a ____ dial
- activity site and acts as a ____ switch
- makes dNDPs (from NDPs)
- redox
- tyrosine
- NDPs and NTPs
- NADPH
- regulation
- catalytic
- allosteric site
- on/off
- ATP
- dATP
- volume
- on/off
deoxyribonucleottide synthesis:
all the dNDPs are converted to dNTPs by
nucleoside diphosphate kinase just like their NDP cousins
to get from UDP to dTTP, we must go through which intermediate?
2 ways to create dUMP:
- removal of ____ from dUTP
- deamination of ____
dUMP
- PPi
- dCMP
deoxyribonucleotide synthesis:
- dTTP detour
- thymidylate synthase adds a ____ to dUMP to create dTMP
- dihydrofolate is reduced to form ____ through the oxidation of NADPH via dehyrdofolate reductase
- dTTP detour
- methyl
- THF
several chemotherapy drugs acts upon enzymes in the dTTP detour:
- 5-fluorouracil (5-FU) is a ____ ____
- it makes an unusable substrate for ____ ____
- 2 drugs that competitively inhibit dihydrofolate reductase are
- the anti-cancer drug ____
- the antibacterial/antiprotozoan drug ____
- suicide inhibitor
- thymidylate synthase
- methotrexate
- trimethoprim
- methotrexate
salvage and breakdown overview:
- ____ cut in the middle
- ____ chew from the end
- endonucleases
- exonucleases
salvage and breakdown of pyrimidines:
- pyrimidines use ____ and ____ to interconvert between nucleobases and NMPs it two steps
- phosphorylases interconvert between ____ and ____
- kinases convert ____ to ____
- nucleotidases convert ____ to ____
- phosphorylases and kinases
- nucleosides and nucleobases
- nucleosides to nucleotides
- nucleotides to nucleosides
salvage and breakdown:
- purines use ____ to interconvert between ____ and ____ in one step
- adenine phosphoribosyltransferase makes ____
- hypoxanthine-guanine phosphoribosyltransferase (HGPRT or HPRT) makes ____/____
- phosphoribosyltransferases, nucleobases and NMPs
- AMP
- IMP/GMP
salvage and breakdown:
- nitrogenous bases can ben broken down to ____ acid and ____
- uric acid is the final product of ____ catabolism
- beta-ureidopropionic acid can be converted to ____ + CO2 + NH3 to complete ____ catabolism
- uric acid and beta-ureidopropionic acid
- purine
- alanine, pyrimidine
acyclovir:
- binds tightly to ____ thymidine kinase, but will not interact with ____ thymidine kinase
- acyclovir triphosphate can be incroporated into ____ DNA, where it terminates ____
- viral thymidine kinase is not as ____ as human thymidine kinase where it only accepts thymines
- viral, human
- viral, synthesis
- picky
nucleotide metabolism in medicine:
- uric acid, like glutathione is an ____
- uric acid/urate is ____
- urate oxidase solubilzes ____ at the cost of its antioxidant potential
- humans and great apes have ____ urate oxidase genes
- at high concentrations, urate ____
- chronic elevated levels of urate in blood (hyperuricemia) results in uric acid crystals collecting in joints = ____
- symptoms include: ____ , ____ , and ____ ____
- many pathologies can produce gout symptoms, such as ____ deficiency (Lesch-Nyhan Syndrome)
- purines cannot be ____ , only degraded (making more uric acid)
- HPRT is located on ____ -chromosome
- symptoms begin in ____
- antioxidant
- insoluble
- urate
- mutated
- crystallizes
- gout
- HPRT
- salvaged
- X
- infancy
severe combined immunodeficiency disease:
- is a deficiency of ____ ____ , without it, ____ accumulates
- dAMP is converted to ____ by salvage pathway enzymes
- dATP inhibits ____ ____
- ____ are not produced, DNA cannot be syntheized, (cells (e.g. immune cells) do not proliferate
- adenosine deaminass, dAMP
- dATP
- ribonucleotide reductase
- deoxyribonucleotides
