NUCLEOTIDES LECTURE 2 Flashcards
what is the 1st synthesis cycle of de novo purine synthesis, starting with beta-5-phosphoribosilamine?
- 3 cycles of glycine addition to add 3 atoms
complex regulation - nitrogen from glutamine
- C from N10-formyl THF
- Cyclization
nucleophilic attack by enamine N9 on C=O
what are steps 7-10 in the de novo synthesis of purines?
addition of HCO3- to get a new carbon
N from aspartate in 2 steps:
- N succinyl adduct intermediate
- release of fumarate
this makes AICAR
new C from N10 formyl THF
why is AICA ribotide banned from sports?
nucleoside: acadesine
nucleotide: ZMP
this ribotide stimulates AMP dependent protein kinase and speeds up metabolism
used as a performance enhancing drug and has been banned
how does the final step happen (synthesis of IMP)?
2nd ring closure
dehydration
no ATP required
what is IMP a branch point for
purine base intermediate
branch point for AMP and GMP biosynthesis
what do the synthesis of AMP and GMP need?
AMP uses aspartate and GTP
GP via XMP uses glutamine and ATP
general rule:
amino groups put on, taken off via carbonyls
how are diphosphates made?
made via base specific kinases (not specific for ribose/deoxyribose) (for example adenylate kinase or uridylate kinase)
phosphate comes from ATP
close to thermodynamic equilibrium
how are triphosphates made?
ubiquitous, non specific kinases
nucleoside diphosphate kinase
the phosphate comes from another triphosphate
close to thermodynamic equilibrium
what are the ratios of those reactions?
ratio of diphosphate/monophosphate is the same as triphosphate/diphosphate
the reactions depend on the concentrations of reactants
what is the intracellular ratio of RNA to DNA in E.coli?
roughly 7 times more RNA than DNA
what is the intracellular ratio of NTP to dNTP in E.coli?
roughly 7 more times NTPs than dNTPs
what is the intracellular ratio of NTP to NDP in E.coli?
roughly 7 more times NTP than NDP
what is the intracellular ratio of NDP to NMP in E.coli?
roughly 7 more times NDP than NMP
how is purine synthesis regulated?
feedback inhibition by nucleotides
regulation at steps 1 and 2 (making PRPP and 5-phosphoribosylamine)
activation by PRPP
characteristics of tetrahydrofolate
THF
most versatile enzyme cofactor
carries 1 carbon unit in three different oxidation states
either on N5 or N10
carries carbon in 5 different chemical forms
from folic acid found in leaves (foliage)
what are the oxidation levels, the group carried and the THF derivatives for THF?
