Nucleotide Metabolism Flashcards
What are the two main ways purine synthesis is regulated?
- Feedback inhibition. End-products inhibited synthesis.
2. Cross-Regulation. AMP synthesis stimulated by GTP, GMP synthesis stimulated by ATP.
What is the purpose of dUTPase during pyrimidine synthesis?
To breakdown dUTP to dUMP in order to prevent dUTP from incorporating into DNA.
What is the first enzyme used in the synthesis of pyrimidines and what stimulates it?
Carbamoyl phosphate synthetase II. Stimulated by PRPP.
What key antioxidant is produced by the pentose phosphate pathway?
Glutathione (GSH)
What is methotrexate and how does it work?
Drug used to treat cancer. Disrupts purine/pyrimidine synthesis, therefore preventing DNA replication in rapidly dividing cancer cells. Efficacy depends on selective drug uptake.
What are sulfa drugs and how do they work?
Antibiotics that selectively disrupt DNA replication in bacteria. Blocks synthesis of folate by bacteria. Does not effect humans as folate is acquired through the diet.
Why would depriving cells of GMP and dGTP be a target for therapeutic intervention?
It can be targeted to disrupt DNA synthesis in B and T cells. This is useful for preventing rejection of other drugs/interventions.
What is allopurinol and how does it work?
Drug used to treat gout. Targets the enzyme xanthine oxidase to limit the production of uric acid.
Why does uric acid play a key role in gout?
It has an acidic hydrogen and limited solubility in water, leads to deposits of sodium urate in extremities.
Describe severe combined immunodeficiency (SCID).
Genetic disorder where both B and T cells are compromised (bubble boys). Can be caused by a deficiency in Adenosine Deaminase (ADA), which has its highest activity in lymphocytes. Deficiency impairs DNA synthesis.
Describe Lesch-Nyhan syndrome.
Deficiency in HGPRT. Excess GMP and IMP are converted into uric acid instead of salvaged.
Symptoms: self-mutilation, metal retardation, poor muscle control
What is Acyclovir and how does it work?
An anti viral drug. It resembles guanine and blocks DNA synthesis in a virally infected cell.
What enzyme is deficient in Severe Combined Immunodeficiency Syndrome (SCID)?
Adenosine deaminase (ADA)
