Nucleotides Flashcards
Functions of nucleotides:
Energy currency: ATP, GTP Energy carrier: FADH, NADH
Enzyme cofactors - Acetyl CoA (adenine)
Genetic information - DNA, RNA
Hormonal(first messenger) signaling - cyclic nucleotides (second messenger), GTP in G-coupled receptors
Metabolic intermediates
To which of the C-atoms of the sugar is the phosphate/base attached?
Phosphate: 1
Base: 5
Purines (P A G) by numbers:
Adenine: 6-amino purine
Guanine: 2-amino 6-keto purine
Pyrimidines by numbers:
Cytosine: 2-keto 4-amino pyrimidine
Uracil: 2,4 keto pyrimidine
Thymine: 5-methyl uracil
How are phosphates/bases connected to sugars?
Phosphate: Phosphoester bond
Bases: N-glycosidic bond
The enzyme used for Thymidine synthesis:
Source of methyl group:
Thymidylate synthase, methyl group from N5 N10 methylene tetrahydrofolate
Substrates of Thymidine synthase:
Products of Thymidine synthase:
Substrate: N5 N10 methylene tetrahydrofolate and dUMP
Products: 7,8 Dihydrofolate and dTMP
What happens to 7,8 Dihydrofolate?
It is part of the cycle: 7,8 Dihydrofolate reduced to H4 folate -> H4 folate converted back to N5 N10 methylene tetrahydrofolate (CH3 donor for Thymidine syntahse)
Enzyme converting 7,8 Dihydroflae in H4 folate:
dihydrofolate reductase
-> competitive inhibitors: Methotrexate, Aminopterin, Trimethoprim
How can the formation of Thymine (dTMP) be inhibited?
-Fluorouracil: has Flourid at position 5 instead of -CH3 and blocks the active site of Thymidine synthase
-inhibition of H4 Folate formation (7,8 Dihydrofolate -> H4 folate)
by Methotrexate, Aminopterin, Trimethoprim -> mimicking folate