Lecture 30 - Nucleotide Formation Flashcards
What is PRPP and where does it come from?
L30 S5
5-phospho-α-D-ribosyl-1-pyrophosphate
Derived from ribose-5-phosphate (pentose phosphate pathway) and can be used in synthesis of all neucleotides
What are the characteristics of pyrimidine synthesis (PRPP dependency, branched/linear, location, and precursors)?
L30 S6
PRPP independent
Linear pathway
Occurs in cytoplasm
Precursors:
- Gln
- Asp
- HCO3
What are the characteristics of purine synthesis (PRPP dependency, branched/linear, location, and precursors)?
L30 S15
PRPP dependent (base synthesized on PRPP)
Branched pathway (inosine is made first and then either GMP or AMP)
Occurs in cytoplasm
Precursors:
- Gln (NH3)
- Aspartate and glycine
- N10-formal-THF
- HCO3
How is UMP synthesized and what regulates it?
L30 S7
Formed from HCO3-, glutamine (NH3), and aspartate
Base is formed without PRPP
Promoters:
-ATP (ATP pairs with UMP, dTTP comes from UMP, so if there is excess ATP more UMP is needed)
Inhibitors:
-CTP (CTP is made from UMP so if there is excess CTP, more UMP is not needed)
How is CTP synthesized and what regulates it?
L30 S7
CTP is made from UTP (unidirectional pathway)
Base is formed without PRPP
Promoters:
-GTP (cytosine pairs with guanine so if there is excess GTP, more CTP is needed)
Inhibitors:
-CTP (inhibits excessive production of itself)
How is GMP synthesized and what regulates it?
L30 S25
Synthesized from IMP (branched pathway)
Additional NH3 is from glutamine (bond energy from GTP) at secondary carbonyl which is from water
IMP synthesized with PRPP
Inhibitors:
-GTP (inhibits excessive production of itself)
How is AMP synthesized and what regulates it?
L30 S25
Synthesized from IMP (branched pathway)
Carbonyl replaced by NH3 which is from aspartate (bond energy from ATP)
IMP synthesized with PRPP
Inhibitors:
-ATP (inhibits excessive production of itself)
What is ATCase and what is significant about it?
L30 10
Aspartate transcarbamoylase
Regulatory enzyme of pyrimidine synthesis (carbonyl + aspartate -> carbamoyl aspartate)
Promoted by:
-ATP
Inhibited by:
-CTP
What is dihydroortate dehydrogenase and what is significant about it?
L30 S11
Enzyme of pyrimidine synthesis (dihydroorotate -> orotate)
Found in the mitochondria and uses FMN producing FMNH2 which is passed to Q of the ETC
What is dihydroorotase and what is significant about it?
L30 S11
Enzyme of pyrimidine synthesis (carbamoylaspartate -> dihydroorotate + H20)
Closes ring
Opposite of a hydrolase (she really like this
What is CTP synthetase and what is significant about it?
L30 S15
Regulatory enzyme of pyrimidine synthesis (UTP -> CTP)
Promoted by:
-GTP
Inhibited by:
-CTP
What is UMP synthase and what is significant about it?
L30 S12
Enzyme of pyrimidine synthesis (add PRPP to orotate and converts orotate to uracil)
What are nucleotide monophosphate kinases and what is significant about them?
L30 S14
Phosphorylates monophosphates to diphosphates
Unique to each NMP
What are nucleotide diphosphate kinases and what is significant about them?
L30 S14
Phosphorylates diphosphates to triphosphates
Not specific for certain NDP
What is the purinosome and what is significant about it?
L30 S23
Enzyme of purine synthesis.
Consists of 6 enzymes that perform the 10 reactions of purine synthesis
What is rNDP reductase and what is significant about it?
L30 S28
Converts NDPs to dNDPs (or NTPs to dNTPs)
What is special about dTTP synthesis?
L30 S27
Must go through dUMP from dUDP or dCDP first
Differentiate between endonucleases and exonucleases.
L30 S39
Endonuclease:
-cuts in the middle
Exonuclease:
-cuts from the ends
What results from HPRT deficiency?
L30 S48
Leach-Nyhan syndrome
What results from adenosine deaminase deficiency?
L30 S49
SCID
What results from UMP synthetase deficiency?
L30 S13
Megaloblastic anemia
What is the significance of acyclovir?
L30 S42
Is accepted by viral thymidine kinase and acyclovir triphosphate acts as a terminator of DNA synthesis if incorporated into DNA
