Blake_Biochem_21_Nucleotide Metabolism

Question 1

Pyrimidine Nucleotide Catabolism:

UTP ptwy:

Substrate/Enzyme

Answer 1

• (d)UTP to (d)Uridine/nucleotidase
• (d)Uridine to Uracil/Uridine phosphorylase
• Uracil to ß-alanine
  
  • ​P_i (in), ribose 1-P (or 2-deoxyribose 1-P) (out)
• ß-alanine to Malonyl CoA (ketogenic)

Question 2

Pyrimidine Nucleotide Catabolism:

dTTP

• Substrates to products/Enzymes:
  
  • other substrates/products

Answer 2

• dTTP to Deoxythymidine/nucleotidase
• Deoxythymidine to Thymine/Uridine phosphorylase
• Thymine to ß-aminoisobutyrate
  
  • ​P_i (in) 2-deoxyribose 1-P (out)
• ⇒ß-aminoisobutyrate
• ⇒Methylmalonyl CoA (glucogenic) +Succinyl CoA (glucogenic)

Question 3

Purine Nucleotide Catabolism:

GMP ptwy

substrate/Enzyme

Answer 3

• GM​P to Guanosine/nucleotidase
• Guanosine to Guanine/PNP (purine nucleoside phosphorylase)
• Guanine to Xanthine/Guanine deaminase
  
  • P_i (in), Ribose 1-P (out)
• Xanthine to Uric Acid/Xanthine oxidase
• Uric Acid

Question 4

Pyrimidine Nucleotide Catabolism:

CTP ptwy:

Substrate/Enzyme:

Answer 4

• (d)CTP to (d)Cytosine/nucleotidase
• (d)Cytosine to (d)Uridine/ aminohyrolase
• (d)Uridine to Uracil/Uridine phosphorylase
  
  • ​​P_i (in), ribose 1-P (or 2-deoxyribose 1-P) (out)
• Uracil to ß-alanine
• ß-alanine to Malonyl CoA (ketogenic)

Question 5

Purine Nucleotide Catabolism:

Adenosine Ptwy

Substrate/Enzyme

Answer 5

• AMP to Adenosine/nucleotidase
• Adenosine to Inosine/ Adenosine Deaminase (ADA)
• Inosine to Hypozanthine/Purine Nucleoside Phosphorylase (PNP)
• Hypozanthine to Xanthine / Xanthine Oxidase
  
  • • Ribose 1-P
• Xanthine to Uric Acid/ Xanthine Oxidase

Question 6

Purine Nucleotide Catabolism

IMP ptwy

Substrate to products/Enzyme

Answer 6

• AMP to IMP/ AMP deaminase
• IMP to Inosine/ + Phosphate
• Inosine to Hypoxanthine/ PNP
• Hypoxanthine to Xanthine/ Xanthine Oxidase
• Xanthine to Uric Acid/ Xanthine Oxidase

Question 7

Phase I-III: Purine Synthesis:

• Substrate to Products/Enzyme
  
  • +/-
  • byproducts or additional substrate

Answer 7

• I. a-_D-ribose 5P to PRPP/PRPP synthease
  
  • +P_i/ - Purine Nucleotides (GMP, AMP, IMP)
  • ATP⇒AMP
• II: PRPP to PRA/glutamine PRPP Amidotransferase
  
  • + PRPP/ - Purine Nucleotides (GMP, AMP, IMP)
  • Gln⇒Glu, ⇒PP_i
• III: PRA to IMP/ 9 rxns (tetrahydrofolate: N¹⁰-fTHF)
  
  • - Methotrexate
  • ​CO₂, Gly, Gln, Asp, N¹⁰-fTHF (additional substrates)

Question 8

Phase IV Purine Synthesis:

GMP ptwy

• Substrate to Products/Enzyme
  
  • +/-
  • Byproducts or additional substrates

Answer 8

• IMP to XMP (xanthosine phosphate)/ IMP dehyrogenase
  
  • • GMP
  • NAD⁺ ⇒ NADH
• XMP to GMP/ GMP synthase
  
  • Gln ⇒Glu, ATP⇒AMP +PP_i
• GMP to GDP/ 2 paths
  
  1. ​GDP to dGDP/ribonucleotide reductase
     
     • dGDP to dGTP
  2. GDP to GTP

Question 9

Phase IV Purine Synthesis:

AMP ptwy

• Substrate to Products/Enzyme
  
  • +/-
  • Byproducts or additional substrates

Answer 9

• IMP to adenlylosuccinate MP/ adenylosuccinate synthease
  
  • -AMP
  • Asp ⇒, GTP⇒GDP
• Adenylosuccinate MP to AMP
  
  • ​⇒Fumarate (used in TCA)
• AMP to ADP/2 paths
  
  1. ADP to dADP/ribonucleotide reductase
     
     • ​dADP to dATP
  2. ​ADP to ATP

Question 10

Phase I Pyrimidine Synthesis:

4 steps

• Substrate to Products/Enzyme
  
  • +/-
  • Byproducts or additional substrates

Answer 10

• Gln to Carbamoylphosphate/Carbaboyl Phosphate Synthease II
  
  • +PRPP/-UTP
  • ⇒Glu, 2ATP⇒2ADP, HCO₃^-(in), P_i (out)
• Carbanoylphosphate to Carbamoyl Aspartate/ Aspartate transcarbomylase
  
  • Asp(in), P_i (out)
• Carbamoyl Aspartate to Dihydroorotate/ dihydroorotase
  
  • ​H₂O (out)
• Dyhydroorotate to Orotate/ dyhydroorotate dehydrogenase

Question 11

Phase II Pyrimidine Synthesis:

2 steps

• Substrate to Products/Enzyme
  
  • +/-
  • Byproducts or additional substrates

Answer 11

• Orotate to OMP/ UMP synthase
  
  • PRPP (in), PP_i (out)
• OMP to UMP/ UMP synthase
  
  • H₂O (in), HCO₃^- (out)

Question 12

Phase III Pyrimidine Synthesis:

dTTP

5steps

• Substrate to Products/Enzyme
  
  • +/-
  • Byproducts or additional substrates

Answer 12

• UMP to UDP/ Phosphorylase
  
  • P_i (in)
• UDP to dUDP/ ribonucleotide reductase
  
  • H₂O (out)
• dUDP to dUMP/ UTP kinase
• dUDP to dUTP to dUMP/ dUTPase
• dUMP to dTMP/Thymidylate synthase
  
  • N⁵,N¹⁰-mTHF⇒Dihydrofolate
• dTMP to dTDP to dTTP

Question 13

Phase III Pyrimidine Synthesis

dCTP

5steps

• Substrate to Products/Enzyme

Answer 13

• UMP to UDP/ ? phosphorylase
• UDP to UTP/ ? phosphorylase
• UTP to CTP/ CTP synthase
• CTP to CDP/ ? kinase
• CDP to dCDP/ ribonucleotidase reductase
• dCDP to dCTP/ ? phosphorylase

Question 14

Purine Nucleotide Salvage Pathway

Answer 14

• Adenine to AMP/ Adenine Phosphoribosyl Transferase (APRT)
  
  • PRPP to PP_i
• Guanine (or Hypoxanthine) to GMP (or IMP)/ Hypoxanthine-guanine phophorybosyl-transferase (HGPRT)
  
  • PRPP to PP_i

Question 15

Pyrimidine Nucleotide Salvage Pathway

Answer 15

• Uracil
  
  • Uracil to Uridine/ Uridine phosphorylase
    
    • Ribose 1-P to P_i
  • _​Uridine to UMP/ Kinase
  • UMP to UDP to UTP/ Phoshphorylase
• Thymine
  
  • Thymine to Deoxythymidine/ thymidine phosphorylase
    
    • 2-deoxyribose 1-P to P_i
  • Deoxythymidine to dTMP/ thymidine kinase
  • dTMP to dTDP to dTTP/ Phosphorylase

Question 16

Pyrimidine Nucleotide Catabolism

CTP

Answer 16

• (d)CTP to (d)Cytosine/ nucleotidase
• (d)Cytosine to (d)Uridine/ aminohydrolase
• (d)Uridine to (d)Uracil/Uridine phosphorylase
• Uracil to ß-alanine
  
  • ​Pi (in), ribose 1-P (or 2-deoxyribose 1-P) (out)
• ⇒ß-alanine
• ⇒Malonyl CoA (ketogenic)