1-C Metabolism Flashcards
What are 2 key 1-C donors?
1) THF (tetrahydrofolate - de novo purine synthesis; thymidylate synthesis)
2) SAM (S-adenosylmethionine: epinephrine synthesis; DNA methylation)
What is the process in which the 1-C donors are involved?
DNA methylation nucleotide synth epi synth AA synth complex lipid synth secondary metabolites
How is THF synthesized in humans? bacteria?
Humans: Folate –> DHF –> THF
Enzyme: DHFR
Bacteria (additional step): PABA –> Folate –> DHF –> THF
Additional enzyme: DHPS
What is the mech of action of methotrexate?
competitively binds to DHFR, blocking THF production –> no THF –> no purines/thiamines –> cell death
What is the mech of action of aminopterin?
inhibit DHFR in bacteria
What is the mech of action of trimethoprim?
inhibit DHFR in humans
What is the mech of action of sulfonamides?
inhibit DHPS in bacteria
How is N10-formyl-THF synthesized?
Formate + THF
What is the role of N10-formyl-THF in purine nucleotide synthesis?
x
How is N5.N10-Methylene-THF synthesized?
Glycine or Serine or Formaldehyde + THF
What is the role of N5.N10-Methylene-THF in thymidylate synthesis?
substrate for thymidylate synthase, which also requires conversion of dUMP to dTMP
this conversion won’t happen with folate deficiency –> megablastic anemia
How is SAM synthesized?
L-methoninie + ATP –> SAM + Pi
Enzyme: SAM Synthetase
What is SAM’s role in epinephrine metabolism?
substrate in production
How is SAM metabolized?
x
What is the folate trap?
x
