NUCLEOTIDES Flashcards

1
Q

Structural analog of folate, selectively inhibits bacterial dihydrofolate reductase

A

Trimethoprim

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2
Q

Affected enzyme in Severe Combined Immunodeficiency Syndrome (SCID)

A

Adenosine Deaminase

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3
Q

Donors of atoms for PYRIMIDINE SYNTHESIS

A
  • Glutamine (Q)
  • Aspartate (D)
  • CO2
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4
Q
  • Enzyme Deficiency: HGPRT
  • Clinical Presentation:
    • ↑ PRPP and uric acid leads to gout
    • Self-mutilation, mental retardation o X-linked disease
A

LESCH-NYHAN SYNDROME

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5
Q

Synthesis of Purine

A
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6
Q
A
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7
Q

o Accumulation of deoxyadenosine derivatives (↑ dATP) inhibits ribonucleotide reductase, leading to lack of DNA synthesis in immune cell precursors

o May present as severe combined immunodeficiency

o Absent thymus, no T-cell or B-cell production

(lymphocytopenia)

o Death before age 2 because of overwhelming infection

o Treat with bone marrow transplant, gene therapy

A

ADENOSINE DEAMINASE DEFICIENCY

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8
Q

How many rings does a pyrimidine have?

A

1

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9
Q

NucleoSides

A

BS: Base + Sugar only

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10
Q

rate limiting enzyme for PYRIMIDINE SYNTHESIS

A

Carbamoyl phosphate synthetase II

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11
Q

Donors of atoms of PURINE SYNTHESIS

A
  • glutamine (Q)
  • Aspartate (D)
  • CO2
  • Glycine (G)
  • N10-formyltetrahydrofolate (Vit B9)
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12
Q

Nucleotides composition

A

BSP: Base + Sugar + Phosphate.

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13
Q

Reversible inhibitor of IMP dehydrogenase, depriving T and B lymphocytes of nucleic acids

A

Mycophenolate

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14
Q

Purine Salvage Pathway

A
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15
Q
  • Converts dUMP to thymine
  • Cofactor: N 5 ,N 10 -methylene tetrahydrofolate
  • Inhibited by 5-fluorouracil
A

Thymidylate synthase

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16
Q

Pyrimidine synthesis

A
17
Q

Metabolically converted to 5-FdUMP, which inhibits thymidylate synthase

A

5-fluorouracil

18
Q
  • Converts ribose 5-phoshate to its activated form, 5- phosphoribosyl-1-pyrophosphate (PRPP)
  • Energy requirement: ATP → AMP
  • PRPP is the donor of ribose 5-phosphate of nucleotides, whether they are synthesized de novo or through salvage patwhays
A

PRPP Synthase

19
Q
  • Inhibits xanthine oxidase
  • Non-purine inhibitor of xanthine oxidase
A

Allopurinol

Febuxostat

20
Q

inhibit dihydropteroate synthase

A

Sulfonamides

21
Q
  • Enzyme Deficiency: Glucose 6-phosphatase
  • Clinical Presentation:
    • ↑ ribose 5-phosphate leads to purine overproduction and hyperuricemia, and thus, gout
A

VON GIERKE DISEASE

*G6Phosphatase is needed in glycogenolysis/ gluconeogenesis in the liver for G6P to be converted to G (glucose). If that enzyme is missing, G6P will be shunted towards HMP (so dadami R5P na pwede pang produce ng nucleotides eventually madami dami need idegrade → hyperuricemia)

22
Q

connects base to sugar

A

B-N-glycosidic bond

23
Q
A
24
Q

Affected enzyme in Lesch nyhan Syndrome

A

HGPRT

25
Q

How many rings does a purine have?

A

2

26
Q

bond that joins 2 nucleotides; condensation reaction; dehydration reaction

A

Phosphodiester bond

27
Q

connects Phosphate to Sugar

A

Phosphoester Bond

28
Q
A
29
Q

parent molecule of purine synthesis

A

Inosine monophosphate (IMP)

30
Q

what are the common substrates for Purine and pyrimidine synthesis?

A

• Glutamine

• Aspartate

• Carbon dioxide

31
Q

Inhibits dihydrofolate reductase, which reduces the tetrahydrofolate supply for the synthesis of thymine

A

Methotrexate

32
Q
  • Enzyme Deficiency: Orotidine phosphate decarboxylase or orotate phosphoribosyl-transferase (UMP Synthase)
  • Clinical Presentation:
    • Impaired pyrimidine synthesis
    • Poor growth
    • Megaloblastic anemia
    • Orotate in the urine
    • Treat with uridine
A

OROTIC ACIDURIA

*These two enzymes belong to UMP synthase Note: if orotic aciduria + anemia = think UMP synthase deficiency! (pyrimidine pathway issue). But: if orotic aciduria + hyperAmmonemia and No anemia = think OTC deficiency! (urea cycle issue)

33
Q

parent molecule of pyrimidine synthesis

A

Orotidine monophosphate (OMP)

34
Q
  • Enzyme Deficiency: Dihydropyrimidine dehydrogenase
  • Clinical Presentation:
    • Combined uraciluria-thyminuria
    • Impaired formation of β-alanine and of β-aminoisobutyrate
A

β-HYDROXY-BUTYRIC ACIDURIA

35
Q

Rate limiting enzyme for PURINE SYNTHESIS

A

PRPP glutamyl amidotransferase