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Medical Biochemistry > Purine/Pyrimidine Metabolism > Flashcards

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)?

A

Liver

24
Q

What enzyme can transfer hypoxanthine to PRPP?

A

HGPRT

25
Q

What is the final product of Purine degradation?

A

Uric Acid

26
Q

What is Lesch-Nyah’s Syndrome?

A

HGPRT r other purine salvage enzyme Deficiency (X-linked recessive)

  • Spastic cerebral palsy
  • Self mutilation
  • Hyperuricemia/gout
27
Q

What results fro Adenosine deaminase deficiency?

A
  • 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
Q

What are the important enzymes in purine degradation?

A
  1. Purine Nucleoside phosphorylase (Inosine —> Hypoxanthine)
  2. Adenosine deaminase (Adenosine —> Inosine)
  3. Xanthine Oxidase (Xanthine —> Uric Acid)
29
Q

What is the action of Allopurinol?

A

Blocks Xanthine Oxidase

30
Q

Describe pathology of Gout.

A
  • 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
Q

What are the reactant molecules which form the pyrimidine ring? What is initially formed from them? The enzyme?

A

Gln+HCO3+H2O+ATP —> Carbamoyl Phosphate

  • CPS II
32
Q

What is formed from carbamoyl phosphate in pyrimidine synthesis? Enzyme? Other reactants?

A

Carb-Pho + Aspartate —> Carbamoyl Aspartic Acid

  • Aspartate Transcarboxylase
33
Q

What type of enzyme is Aspartate transcarboxylase?

A

ATCase

34
Q

What is converted from Carbamoyl Aspartate acid in pyrimidine synthesis? Enzyme?

A

CAA —> Orotate

  • Dihydroorotase
35
Q

What is made from orotate in pyrimidine synthesis? Enzyme? Other reactants?

A

Orotate + PRPP —> OMP

  • OPRT
36
Q

What is the final precursor in Pyrimidine synthesis? Enzyme?

A

OMP —> UMP

  • UMP Synthase
37
Q

Describe pathology of Orotic aciduria.

A
  • 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
Q

What is the action of Hydroxyurea?

A

Blocks DNA synthesis by inhibiting ribonucleotide reductase

39
Q

What else is needed for Robinucleotide reductase to function?

A

Reducing agents:

  • Thioredoxin
  • Glutathione
40
Q

Which subunits of ribonucleotide reductase is the catalytic sites?

A

R1 subunits

  • One os On/Off
  • One is specificity
41
Q

What is special about the R2 subunit of Ribonucleotide Reductase?

A

R2 have a Tyr radical

42
Q

What inhibits ribonucleotide reductase?

A

dATP

43
Q

Describe the production of CTP from UTP

A

UTP + Gln + ATP —> CTP

-CTP Synthase

44
Q

What are the Regulators of CPS II?

A

PRPP + ATP —> Allosteric activators

CTP —> Inhbiitor

45
Q

What is AZT?

A
  • Blocks DNA Polymerization
  • Very similar to thymidine
  • No 3’-OH; NH3 group instead
46
Q

What are Pyrimidines broken down to?

A

Uridine —> Ribose-1P —> Uracil —> Beta-Alanine

Medical Biochemistry (26 decks)

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