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Biochemistry > nucleotide metabolism 2 > Flashcards

nucleotide metabolism 2 Flashcards

1
Q

all nucleoside X-phosphates are ____

dNXP means ____ is sugar, NXP means ____ is sugar

A

nucleotides

deoxyribose, ribose

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2
Q

DNA nucleotides are dervied from

A

RNA nucleotides

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3
Q

important precursor for all nucleotides is

A

PRPP

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4
Q

de novo synthesis of ribonucleotides - pyrmidines:

  • forms nitrogenous base:
  • ____ pathway
  • occurs in ____
  • precursors used
    • ____ from ____
    • ____
    • ____
  • allosteric regulation
    • ____ inhibits (C)
    • ____ activates (A/G)
A
  • independent of PRPP
  • unidirectional
  • cytoplasm
    • NH3 from Gln
      • Asp
      • HCO3-
    • pymidine
      • purine
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5
Q

de novo synthesis of ribonucleotides - purines:

  • form nitrogensous base:
  • ____ pathway
  • occurs in ____
  • precursers used
    • ____ from ____
    • ____
    • ____
    • ____
    • ____
  • regulation: feedback inhibtion b ____
A
  • on PRPP
  • branched
  • cytoplasm
    • NH3 from Gln
      • Gly
      • Asp
      • N10 - formyl-THF
      • HCO3-
  • purines
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6
Q

carbamoyl phosphate synthetase II (CPSII):

  • used in ____ synthesis
  • part of ____ complex
  • bicarbonate → ____ → ____ → ____
  • NH3 (from glutamine) → ____ → ____
  • activators:
  • inhibitors:
A
  • pyrimidine
  • CAD
  • carboxyphosphate → carbamic acid → carbamoyl phosphate
  • PRPP and ATP
  • UTP
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7
Q

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 ____
A
        • (1) ATP
          • (2) CTP
        • (3) ring
    • (4) mitochondria
    • (5) orotate
      • (6) uracil
  • specific
    • (7) UDP
  • broad
    • (8) CTP
      • (9) triphosphate
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8
Q

de novo synthesis of ribonucleotides - purines:

  1. ​reactions 1-3 forms the 5 membered ring
    1. swaps PPi of PRPP for NH3 from ____
    2. adds ____
    3. adds a formyl group from ____ to complete the ring
  2. reactions 4-10 form the 6 membered ring
    1. adds an NH3 from ____ to start the second ring
    2. closes the ____-membered ring
    3. adds CO2 from ____, first to Gln then to Gly
    4. adds ____ at the carboxyl
    5. releases ____
    6. second addition on a formyl group from another ____ completing the 6 membered ring
    7. closes the 6 membered ring forming ____
A
    1. Gln
    2. Glycine
    3. THR
    1. Gln
    2. 5
    3. HCO3-
    4. CO2
    5. Asp
    6. fumarate
    7. THF
    8. hypoxanthine
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9
Q

in vertebrates, purines are made in the

A

purinosome

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10
Q

branch point for purine synthesis

A

inosine monophosphate (IMP)

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11
Q

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 ____
A
  • AMP
    • GTP
    • NH3 from Asp
    • fumarate
    • AMP
  • GMP
    • ATP
    • NH3 from Gln
    • GMP
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12
Q

in both pyrimidine and purine synthesis, nucleoside monophosphate kinases are ____ to each NMP

in both pyrimidine and purine synthesis, nucleoside diphosphate kinase has ____ specificity

A

specific

broad

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13
Q

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 ____
A
  • UMP synthetase
  • orotate
  • B9/B12
  • divide
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14
Q

UMP synthetase removes PPi when ____ is added to ____ and decarboxylates orotate to form ____

A

orotate

PRPP

uracil

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15
Q

deoxyribonucleotide synthesis overview:

converting ribose to deoxyribose requires a ____ reaction

deoxyribonucleotides are created from their respective ____

pyrimidines take a ____

A

reduction

NDPs

detour

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16
Q

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
A
  • makes dNDPs (from NDPs)
  • redox
  • tyrosine
  • NDPs and NTPs
  • NADPH
  • regulation
    • catalytic
    • allosteric site
      • on/off
        • ATP
        • dATP
      • volume
17
Q

deoxyribonucleottide synthesis:

all the dNDPs are converted to dNTPs by

A

nucleoside diphosphate kinase just like their NDP cousins

18
Q

to get from UDP to dTTP, we must go through which intermediate?

2 ways to create dUMP:

  • removal of ____ from dUTP
  • deamination of ____
A

dUMP

  • PPi
  • dCMP
19
Q

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
A
  • dTTP detour
    • methyl
    • THF
20
Q

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 ____
A
  • suicide inhibitor
    • thymidylate synthase
    • methotrexate
      • trimethoprim
21
Q

salvage and breakdown overview:

  • ____ cut in the middle
  • ____ chew from the end
A
  • endonucleases
  • exonucleases
22
Q

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 ____
A
  • phosphorylases and kinases
    • nucleosides and nucleobases
    • nucleosides to nucleotides
    • nucleotides to nucleosides
23
Q

salvage and breakdown:

  • purines use ____ to interconvert between ____ and ____ in one step
  • adenine phosphoribosyltransferase makes ____
  • hypoxanthine-guanine phosphoribosyltransferase (HGPRT or HPRT) makes ____/____
A
  • phosphoribosyltransferases, nucleobases and NMPs
  • AMP
  • IMP/GMP
24
Q

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
A
  • uric acid and beta-ureidopropionic acid
    • purine
    • alanine, pyrimidine
25
Q

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
A
  • viral, human
  • viral, synthesis
  • picky
26
Q

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 ____
A
  • antioxidant
  • insoluble
  • urate
  • mutated
  • crystallizes
  • gout
  • HPRT
    • salvaged
    • X
    • infancy
27
Q

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
A
  • adenosine deaminass, dAMP
  • dATP
  • ribonucleotide reductase
    • deoxyribonucleotides

Biochemistry (32 decks)

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