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Biochemistry Final Review > Ford (Nucleotide Metabolism) > Flashcards

Ford (Nucleotide Metabolism) Flashcards

1
Q

What is the important precursor for all nucleotides?

A

PRPP

Ribose-5-phosphate –> PRPP (PRPP synthetase)

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2
Q

Pyrimidines

A
  • nitrogenous bases INDEPENDENT of PRPP
  • unidirectional pathway
  • cytoplasmic
  • precursors: NH3 from Gln, Asp, HCO3
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3
Q

CAD

A
  • multifunctional, eukaryotic protein performs functionsL
  1. Carbamoyl phosphate synthetase II (CPSII)
    • has channel for glutamine
  2. Aspartate transcarbamoylase (ACTase)
    • has two allosteric regulators (ATP +/CTP -)
  3. Dihydroorotase
    • closes the ring (hydrolase in reverse)
    • dihydroortase dehydrogenase located in mitochondria
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4
Q

Megaloblastic Anemia

A
  • occurs when cells FAIL TO DIVIDE
  • common: B9/B12 deficiencies

Hereditary Orotic Aciduria

  • excessive orotate in urine
  • megaloblastic Anemia that fails to respond to B9/B12 treatment

DEFICIENCY OF UMP SYNTHETASE

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5
Q

Purines

A
  • form nitrogenous base on PRPP
  • branched pathway
  • cytoplasmic
  • precursors: NH3, Gly, Asp, N10-formyl-THF, HCO3

Regulation: feedback inhibition by purines

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6
Q

Purines - Purinosome

A

6 enzymes perform 10 reactions

  • 1,4,8 –> 3 individual proteins
  • 2,3,5,6,7,9,10 –> 3 multifunctional proteins

2 additional enzymes provide N10-Formyl-THF

proximity facilitates flow

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7
Q

Purines - Branching off from IMP

A
  1. AMP –> uses GTP for energy
    - replace carbonyl w/NH3 from Asp
    - releases fumarate
    - AMP inhibited
  2. GMP –> uses ATP for energy
    - redox w/ water to make 2nd carbonyl, then replaces with NH3 from Gln
    - GMP inhibited
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8
Q

Ribonucleotide Reductase Regulation

A
  1. Activity Site –> allosteric
    • ON = ATP
    • OFF = dATP (alter subunit contacts)
  2. Specificity Site
    • dATP –> pyrimadines preferred
    • dTTP –> GDP (+), pyrimadines (-)
    • dGTP –> ADP (+), pyrimadines (-)
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9
Q

Antivirals (Acyclovir)

A

Viral Thymidine Kinase accepts purines as well as T’s

Acyclovir binds tightly to viral Thymidine Kinase, does not react with human TK
- incorporated into viral DNA, terminates synthesis

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10
Q

Uric Acid

A
  • antioxidant
  • uric acid/urate is insoluble
  • Urate Oxidase solubilizes urate, at cost of antioxidant potential
    • genes mutated in humans and great apes
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11
Q

Gout

A
  • high concentrations = urate crystallizes
    • chronic elevated lvls of urate in blood (hyperuricemia) –> uric acid crystals in joints (GOUT)
    • inflammation, arthritis, joint degradation

HPRT deficiency (Lesch-Nyhan Syndrome)

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12
Q

SCID

A

Severe Combined Immunodeficiency Disease

 - Adenosine Deaminase deficiency
 - w/o --> dAMP accumulates (converted to dATP by salvage pathway)
 - dATP inhibits ribonucleotide reductase

Deoxyribonucleotides NOT produced, DNA NOT synthesized, cells do not proliferate

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13
Q

Ring Structure of Pyrimidines

A
  • Glutamine: provides 1 N
  • CO2: provides 1 C
  • Aspartate: provides 1 N and 3 carbons
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14
Q

Carbomoyl Phosphate Synthetase II

A
  • makes bicarbonate into carbamoyl phosphate
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15
Q

Aspartate transcarbamoylase (ATCase)

A
  • adds aspartate to carbamoyl phosphate

- creates carbamoylaspartate

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16
Q

Dihydroorotase and Dihydroorotate Dehydrogenase

A
  • dihydroorotase closes ring (hydrolase in reverse) = dihydroorotate
  • dehydrogenase changes dihydroorotate into orotate
17
Q

UMP Synthetase

A
  1. removes PPi when orotate added to PPRP

2. decarboxylates orotate to form uracil

18
Q

Nucleoside monophosphate and diphosphate kinases

A

monophosphate: specific to each NMP
diphosphate: broad specificity

19
Q

CTP synthetase

A
  • similar to ATCase (GTP/ATP act, CTP inactivates)

- changes UTP to CTP

20
Q

Ring Structures of Purines

A

5 membered ring:

  • Glycine: 1 N and 2 Cs
  • N-formyl THF: 1 C
  • Glutamine: 1 N

6 membered ring:

  • Aspartate: 1 N
  • N-formyl THF: 1 C
  • Glutamine: 1 N
  • CO2: 1 C
21
Q

Ribonucleotide Reductase

A
  • reduction reaction that converts ribose to deoxyribose

- NADPH provides necessary electrons for redox rxns

22
Q

2 ways to created dUMP

A
  1. removal of PPi from dUTP

2. deamination of dCMP

23
Q

Thymidylate Synthase (dUMP)

A

adds methyl to dUMP to create dTMP

24
Q

Pyrimidine Salvage

A
  • use phosphorylases and kinases to salvage in 2 steps
  • phosphorylases make NUCLEOSIDES
  • kinases make NUCLEOTIDES
25
Q

Purine Salvage

A
  • use phosphoribosyltransferases to salvage in 1 step
26
Q

Types of Phosphoribosyltransferases (2)

A
  1. Adenine –> make AMP

2. Hypoxanthine-Guanine (HGPRT/HGPT) –> IMP/GMP

27
Q

Breakdown of Nitrogenous bases (2 end products)

A
  1. Uric acid (purine catabolism)

2. B-Ureidopropinoic acid converted to alanine, CO2, NH3 by Ureidopropionase (pyrimidine catabolism)

28
Q

Endonucleases and Exonucleases

A
  1. Endonuclease: cuts nucleic acids from the inside
    - makes oligonucleotides
  2. Exonucleases: cuts oligonucleotides from outside
    - makes nucleoside monophosphates

Biochemistry Final Review (8 decks)

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