Pyrimidine Biosynthesis

• for pyrimidine biosynthesis, first have to make orate base, and then attach phosphoribose to form UMP
• build orate from aspartate, ammonia from glutamine, and bicarbonate as well as PRPP
• DODH = uses FMN as an oxidant, but the method of reoxidation of FMNH2 to FMN differs between bacteria and eukaryotes...

  • bacteria: use NAD+ to oxidize (shown on diagram)
  • eukaryotes: use Q to oxidize, which creates QH2 that can feed into the ETC
• animals regulate pyrimidine biosynthesis at CPSII, the rate determining step; where UDP or UTP inhibits and ATP or PRPP activates
• bacteria regulate pyrimidine biosynthesis at ATCase (not CPS because they only have one, unlike eukaryotes)
• ATCase regulation: has both catalytic and regulatory subunits, where binding at regulatory subunits induces conformational changes (cooperative! either promote R or T state)

  • ATP activates, and promotes the R state
  • CTP inhibits, and promotes the T state
  • UTP can bind on top of already bound CTP to further inhibit