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Purine/Pyrimidine Metabolism Flashcards

1
Q

PRPP Synthesis

  • Reactant
  • Enzyme
  • Other substrates
A

Ribose-5-phosphate —> PRPP

  • PRPP Synthase/ Ribose Phosphate
    Pyrophosphokinase
  • ATP —> AMP
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2
Q

What is the role of PRPP Glutamine Amidotranferase? How is it controlled?

A
  • Takes amino group from Glutamine and converts PRPP to Phosphoribosylamine

Allosterically regulated:

Positive: PRPP

Negative: IMP, AMP, GMP

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3
Q

What is the action of Mercaptopurine?

A

Inhibits PRPP amidotranferase

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4
Q

What pathway is Phosphoribosylamine committed to?

A

De Novo Purine synthesis

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5
Q

What enzyme is used to build purines from Phosphoribosylamine? What other reactants are used?

A

GAR Synthase

  • Gly
  • ATP
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6
Q

After GAR Synthase, what reaction occurs in De novo purine synthesis of IMP?

A

A charged THF is used to transfer a formal group

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7
Q

What high energy molecules are needed for production of AMP/GMP?

A

AMP: requires GTP

GMP: requires ATP

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8
Q

Describe how IMP is used to produce AMP

A

IMP —> Adenylosuccinate —> AMP

  • Adenylosuccinate Synthetase
  • Uses Asp + GTP
  • 2nd step releases Fumarate
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9
Q

Describe how IMP is used to produce GMP.

A

IMP —> XMP —> GMP

Step 1: IMP DH
- Uses H2O, NAD+ -> NADH

Step 2: XMP-GLNG Amidotranferase

  • Gln -> Glu
  • ATP —> AMP + PPi
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10
Q

What are the various origins of the different parts of a purine molecule?

A
  • N3/9 —> Glutamine
  • C2/8 —> Formyl Group
  • C6 —> BiCarb Keto
  • N1 —> Aspartate
  • C4/5, N7 —> Glycine
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11
Q

What is the importance of folate in nucleic acid synthesis?

A
  • Folate needed to produce THF
  • THF important for 1 carbon units transfers —> Amino acids and nucleic acid synthesis

*N10 Formyl THF in NA synthesis

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12
Q

What is used to detoxify methanol poisoning?

A

Folate

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13
Q

What two drugs interact with THF production?

A

Sulfonamides: inhibits folate production

Trimethoprim: Inhibits DHFR Which Conversion DHF to THF

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14
Q

What enzymes are used for Purine Salvage?

A

HGPRT (Guanine breakdown)

APRT (Adenine Breakdown)

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15
Q

What enzyme can also break down a nucleic acid to IMP?

A

HGPRT

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16
Q

What is the significance of the salvage pathways?

A

RBCs —> No nuclei —-> Rely on salivate pathways

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17
Q

What does NDPK catalyze?

A

Conversion of all nucleoside diphosphates to triphosphates

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18
Q

What are the three components of Folate?

A
  • PABA
  • Pteridine ring
  • Glutamate
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19
Q

What does 5-Fluorouracil block?

A

Thymidylate Synthase

Conversion of dUMP —> dTMP

Conversion of N5N10 Methylene THF

20
Q

What does Methotrexate block?

A

Recycling of Folate; DHF reductase

Conversion of DHF —> THF

21
Q

What amino acid is need to convert THF to N5N10THF?

A

Serine —> Glycine

22
Q

Describe pathology of megaloblastic anemia.

A
  • Folate or Vit B12 Deficiency

- Decreased DNA/RNA Synthesis

23
Q

Which organ synthesizes nucleic acids (De novo synthesis)?

24
Q

What enzyme can transfer hypoxanthine to PRPP?

25
What is the final product of Purine degradation?
Uric Acid
26
What is Lesch-Nyah’s Syndrome?
HGPRT r other purine salvage enzyme Deficiency (X-linked recessive) - Spastic cerebral palsy - Self mutilation - Hyperuricemia/gout
27
What results fro Adenosine deaminase deficiency?
- Cannot convert adenosine —> Inosine - Severe combined immunodeficiencies —> Both T and B Cell function - dATP and dGTP not catabolized - Indirect inhibition of ribonucleotide reductase —> Inhibition of DNA synthesis * Autosomal recessive
28
What are the important enzymes in purine degradation?
1. Purine Nucleoside phosphorylase (Inosine —> Hypoxanthine) 2. Adenosine deaminase (Adenosine —> Inosine) 3. Xanthine Oxidase (Xanthine —> Uric Acid)
29
What is the action of Allopurinol?
Blocks Xanthine Oxidase
30
Describe pathology of Gout.
- Hyperuricemia —> Sharp Na+-Urate Crystals in Joints/Kidneys - Podagra and Gouty attacks - Exacerbating factors: Increased Purine consumption/production, Decreased clearance (Dehydration), Obesity, and diabetes - Kidney stenosis and urate nephropathy
31
What are the reactant molecules which form the pyrimidine ring? What is initially formed from them? The enzyme?
Gln+HCO3+H2O+ATP —> Carbamoyl Phosphate - CPS II
32
What is formed from carbamoyl phosphate in pyrimidine synthesis? Enzyme? Other reactants?
Carb-Pho + Aspartate —> Carbamoyl Aspartic Acid - Aspartate Transcarboxylase
33
What type of enzyme is Aspartate transcarboxylase?
ATCase
34
What is converted from Carbamoyl Aspartate acid in pyrimidine synthesis? Enzyme?
CAA —> Orotate - Dihydroorotase
35
What is made from orotate in pyrimidine synthesis? Enzyme? Other reactants?
Orotate + PRPP —> OMP - OPRT
36
What is the final precursor in Pyrimidine synthesis? Enzyme?
OMP —> UMP - UMP Synthase
37
Describe pathology of Orotic aciduria.
- Autosomal recessive - Megaloblastic Anemia - Atypical —> Not a Vit B or Folate deficiency - Inhibition of UMP Synthase —> Decreased Pyrimidine synthesis + Build up of Orotic acid in blood
38
What is the action of Hydroxyurea?
Blocks DNA synthesis by inhibiting ribonucleotide reductase
39
What else is needed for Robinucleotide reductase to function?
Reducing agents: - Thioredoxin - Glutathione
40
Which subunits of ribonucleotide reductase is the catalytic sites?
R1 subunits - One os On/Off - One is specificity
41
What is special about the R2 subunit of Ribonucleotide Reductase?
R2 have a Tyr radical
42
What inhibits ribonucleotide reductase?
dATP
43
Describe the production of CTP from UTP
UTP + Gln + ATP —> CTP -CTP Synthase
44
What are the Regulators of CPS II?
PRPP + ATP —> Allosteric activators CTP —> Inhbiitor
45
What is AZT?
- Blocks DNA Polymerization - Very similar to thymidine - No 3’-OH; NH3 group instead
46
What are Pyrimidines broken down to?
Uridine —> Ribose-1P —> Uracil —> Beta-Alanine

Medical Biochemistry (26 decks)

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