Nucleotide biosynthesis and degradation

Question 1

Where are nucleotides synthesised?

Answer 1

Purines: de novo biosynthesis and and reusing purine bases
Pyrimidines: mainly produced de novo

*Both occur in cytosol of all cells.

Question 2

What are the sources of atoms in a purine ring?

Answer 2

• Aspartate
• Glycine
• Glutamine
• CO2,
• THF (folic acid derivative)

Question 3

Discuss the steps in purine biosynthesis.

Answer 3

End products ATP and GTP.

Question 4

What is the common intermediate of AMP and GMP.

Answer 4

IMP (Inosine monophosphate)

Question 5

What are the sources of atoms in a pyrimidine ring?

Answer 5

• Amide nitrogen (R group) of glutamine
• Aspartic acid
• CO2

Question 6

Discuss the steps in pyrimidine biosynthesis.

Answer 6

End products CTP and dTTP.

Question 7

What is the common intermediate of CTP and dTTP?

Answer 7

UMP, uridine monophosphate

Question 8

How are pyrimidines (single ring) broken down?

Answer 8

• Bases are broken down to simple carbon skeletons
  (b-alanine or b-aminoisobutyrate) and degraded.

Question 9

How are purines (2 rings) broken down?

Answer 9

• Bases are either reused (salvage) or degraded
  Xantine - uric acid - excretion

Question 10

What is the clinical relevance of inhibiting dTMP synthesis via chemotherapy drugs?

Answer 10

• They prevent cell division by inhibiting DNA replication
• E.g methotrexate inhibits dihydrofolate reductase DHFR

Question 11

What happens in excessive breakdown of purine bases?

Answer 11

• An excess of uric acid which can precipitate as urate crystals and lead gout.
• These crystals cause inflammation & swelling in joint = ^ pain.