We next investigated the biosynthetic fates of aspartate and found:
Aspartyl tRNA charge = OK
Purine nucleotides = OK
ASN = OK - Rebounds with ASP
Pyrimidine nucleotides = Depleted at the first step (ATCase, which makes Carb-ASP) - and stays depleted even with rebounding ASP:
Aspartyl tRNA charge = OK
Purine nucleotides = OK
ASN = OK - Rebounds with ASP
Pyrimidine nucleotides = Depleted at the first step (ATCase, which makes Carb-ASP) - and stays depleted even with rebounding ASP:
Comments
A complete loss of the ASP rebound and a return to the (very reasonable) phenotype of monotonic ASP depletion.
So, SDH loss causes a disproportionate effect on pyrimidine synthesis by impairing ATCase, but why?
https://pubmed.ncbi.nlm.nih.gov/3894357/
Conclusion: succinate competes with diminished ASP at ATCase, blocking pyrimidine synthesis. To our knowledge the first description of this relationship in cells + revealing another potential regulatory function of succinate.