nucleotide metabolism 2

Question 1

all nucleoside X-phosphates are ____

dNXP means ____ is sugar, NXP means ____ is sugar

Answer 1

nucleotides

deoxyribose, ribose

Question 2

DNA nucleotides are dervied from

Answer 2

RNA nucleotides

Question 3

important precursor for all nucleotides is

Answer 3

PRPP

Question 4

de novo synthesis of ribonucleotides - pyrmidines:

• forms nitrogenous base:
• ____ pathway
• occurs in ____
• precursors used
  
  • ____ from ____
  • ____
  • ____
• allosteric regulation
  
  • ____ inhibits (C)
  • ____ activates (A/G)

Answer 4

• independent of PRPP
• unidirectional
• cytoplasm
• • NH3 from Gln
    
    • Asp
    • HCO3-
• • pymidine
    
    • purine

Question 5

de novo synthesis of ribonucleotides - purines:

• form nitrogensous base:
• ____ pathway
• occurs in ____
• precursers used
  
  • ____ from ____
  • ____
  • ____
  • ____
  • ____
• regulation: feedback inhibtion b ____

Answer 5

• on PRPP
• branched
• cytoplasm
• • NH3 from Gln
    
    • Gly
    • Asp
    • N¹⁰ - formyl-THF
    • HCO3-
• purines

Question 6

carbamoyl phosphate synthetase II (CPSII):

• used in ____ synthesis
• part of ____ complex
• bicarbonate → ____ → ____ → ____
• NH3 (from glutamine) → ____ → ____
• activators:
• inhibitors:

Answer 6

• pyrimidine
• CAD
• carboxyphosphate → carbamic acid → carbamoyl phosphate
• PRPP and ATP
• UTP

Question 7

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 ____

Answer 7

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

Question 8

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 ____

Answer 8

1. 1. Gln
   2. Glycine
   3. THR
2. 1. Gln
   2. 5
   3. HCO3-
   4. CO2
   5. Asp
   6. fumarate
   7. THF
   8. hypoxanthine

Question 9

in vertebrates, purines are made in the

Answer 9

purinosome

Question 10

branch point for purine synthesis

Answer 10

inosine monophosphate (IMP)

Question 11

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 ____

Answer 11

• AMP
  
  • GTP
  • NH3 from Asp
  • fumarate
  • AMP
• GMP
  
  • ATP
  • NH3 from Gln
  • GMP

Question 12

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

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

Answer 12

specific

broad

Question 13

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 ____

Answer 13

• UMP synthetase
• orotate
• B9/B12
• divide

Question 14

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

Answer 14

orotate

PRPP

uracil

Question 15

deoxyribonucleotide synthesis overview:

converting ribose to deoxyribose requires a ____ reaction

deoxyribonucleotides are created from their respective ____

pyrimidines take a ____

Answer 15

reduction

NDPs

detour

Question 16

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

Answer 16

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

Question 17

deoxyribonucleottide synthesis:

all the dNDPs are converted to dNTPs by

Answer 17

nucleoside diphosphate kinase just like their NDP cousins

Question 18

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

2 ways to create dUMP:

• removal of ____ from dUTP
• deamination of ____

Answer 18

dUMP

• PPi
• dCMP

Question 19

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

Answer 19

• dTTP detour
  
  • methyl
  • THF

Question 20

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 ____

Answer 20

• suicide inhibitor
  
  • thymidylate synthase
• • methotrexate
    
    • trimethoprim

Question 21

salvage and breakdown overview:

• ____ cut in the middle
• ____ chew from the end

Answer 21

• endonucleases
• exonucleases

Question 22

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 ____

Answer 22

• phosphorylases and kinases
  
  • nucleosides and nucleobases
  • nucleosides to nucleotides
  • nucleotides to nucleosides

Question 23

salvage and breakdown:

• purines use ____ to interconvert between ____ and ____ in one step
• adenine phosphoribosyltransferase makes ____
• hypoxanthine-guanine phosphoribosyltransferase (HGPRT or HPRT) makes ____/____

Answer 23

• phosphoribosyltransferases, nucleobases and NMPs
• AMP
• IMP/GMP

Question 24

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

Answer 24

• uric acid and beta-ureidopropionic acid
  
  • purine
  • alanine, pyrimidine

Question 25

_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

Answer 25

* viral, human * viral, synthesis * picky

Question 26

_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 \_\_\_\_

Answer 26

* antioxidant * insoluble * urate * mutated * crystallizes * gout * HPRT * salvaged * X * infancy

Question 27

_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

Answer 27

* adenosine deaminass, dAMP * dATP * ribonucleotide reductase * deoxyribonucleotides