BIOL302 Class 17 Flashcards
nitrogenous bases
- pyrimidine
- purine
- both are weakly basic
- both are flat/planar molecules (useful to form hydrogen bonds between bases & provides a 3D structure)
Purines
Adenine & Guanine
Pyrimidines
Cytosine, Uracil, Thymine
Nucleic Acid Polymers
DNA: ATG
RNA: UGC
5 prime to 3 prime
nucleosides are building blocks for numerous biological molecules
examples such as cyclic AMP & cGMP are important signaling molecules
NTPS (not just ATP)
Important sources of energy for enzymatic catalysis in metabolism (energizing compounds for chemical transfers)
AMP
a structural component of important coenzymes like NAD(P), coenzyme A, and FAD
cAMP/cGMP and GTP
are important metabolic regulators and signaling molecules (PKA, G-Proteins, etc)
metabolic requirements for nucleotides are met by
1) recycling/salvage pathways
2) dietary intake
3) de novo synthesis from pre-existing metabolites
metabolic fates of dietary nitrogenous bases overlaps with salvage pathways of bases during normal “tunover”
- free bases and 5-P-Ribose can be used to rebuild NTPS (salvage pathways)
- Ribose-P can be synthesized from glucose via Pentose Phosphate Pathway
- there is a constant and rapid turn-over of nucleic acids in a cell, so salvage is essential
PRPP Kinase
- ADP and GDP are negative regulators (PRPP is the limiting substrate in purine synthesis)
- NOT the commitment step since PRPP has multiple metabolic fates (such as the salvage pathway)
where does Ribose-5-Phosphate come from? under what conditions would this sugar become available?
- comes from Pentose Phosphate pathway
- becomes available when there’s a high energy demand & when RNA and DNA need to be made
Purine Biosynthesis
- step by step building of the base onto the activated ribose PRPP
- the eventual cyclization yields Inosine monophosphate (IMP) which is the direct precursor to both AMP and GMP
committed step for purine biosynthesis
Gln-PRPP Amidotransferase
why does it make sense for AMP and GMP to be negative regulators?
They’re the end products **
once inosine is made it is converted to GMP and AMP
- if you dont have sufficient AMP you cant make GMP, if you dont have sufficient GMP you cant make AMP
what do amino acids provide to nucleotide synthesis?
nitrogens
uric acid
anything causing a build up of uric acid concentration in blood or urine past its solubility in these liquids can lead to its precipitation
gout
painful accumulation of uric acid crystal needles
- clogs arteries, especially at the joints
inhibition of xanthine oxidase by allopurinol
prevents uric acid production and allows for xanthine and hypoxanthine to be excreted instead
purine salvage
purines are a major metabolic investment so salvage pathways collect free adenine, hypoxanthine, and guanine bases and convert them back to useful forms (nucleotides) via PRPP
HGPRT is essential for the purine salvage pathways
- disruption of the enzyme by heritable mutation causes lesch-nyhan syndrome (a sex-linked trait since HGPRT is on the x)
- results in build up of uric acid –> gouty arthritis, severe mental retardation and/or behavioral abnormalities at worse
pyrimidine biosynthesis
- unlike purines, the pyrimidine ring is assembled first, and then added to PRPP as a unit
- initial step uses CPSII to make carbamoyl phosphate; built from HCO3- and amide from glutamine
- end-product regulation targets CPSII
- synthesis is essentially coupling of carbamoyl-P to Aspartate, followed by cyclization and transfer to PRPP
Tetrahydrofolate
the methyl carrier for methylation of dUMP by thymidylate synthase
