Nucleotide metab Flashcards
What is used for Purine Nucleotide sythesis that comes from the Pentose Phosphate Pathway?
Ribose sugar
Ribose 5-phosphate
NADH generally helps with _____, while NADPH helps with___.
breakdown, prod. of TCA, drives ATP, Catabolic processes
bulding things, from pentose phosphate pathway
What enzyme does Methotrexate inhibit?
DHFR, in the oxidation of NADPH by DHRF
How does our body balance the amount of Adenine, Thiamine, Guanine, Cytosine?
Feeback and Cross reg. during PURINE nucelotide synth.
IMP, AMP, GMP, products of this pathway, INHIBIT the main guy PRPP’s synth.
Phases of Pyrimidine Nucl. synth?
Phase 1: fabricate orotate ring
Phase 2: Attach PRPP to form UMP
Phase III: Convert UMP to uridine, cytosine, thymidine (doexy)nuleotides
Phases in Purine Synthesis?
- Ribose-5P activation (which comes from PPP)
- Convert PRPP to PRA
* *3. Construct IMP ring
* *4. Convert IMP to adenosine and guanosine (doxy)nucleotides
Acyclovir
terminates DNA replication (lacks 3’-OH group, terminator)
treats sores for Herpes, Chicken pox
Thymidine kinase has more affinity for acyclovir
_____ + _____ = Uric Acid
GMP + AMP eventually in PURINE nucl. catabolism make Uric Acid
What molecule is inhibited to help with gout pts? What enzymes does this affect?
Allopurinol, which affects xanthine oxidase, lowering teh number of xanthine to Uric Acid.
Why does uric acid, but not it’s intermediates before it during Nucl. catabolism cause gout?
It has 3 oxygens
less water soluble (incr. solubility in joint)
three endproducts of pyrimidine nucl. catabolism?
Malonyl CoA, ketogenic
**Beta-aminoisobutyrate (from dTDP and dTTP) make
methylmalonyl CoA
Succinyl CoA
both glucogenic
sources of atoms in Purine bases
CO2, Gln, Gly, Asp, N10-formyl THF
pyrimidine atom sources
HCO3-, Gln, Asp, N5-methylene THF
What comes before ATP, GTP (RNA) and dATP, dGTP(DNA) during purein ring synth?
IMP
It is converted to AMP or GMP
Commited step in purine synthesis?
- fomration of phosphoribosyl amine
glutamine: phosphoribosyl pyrophosphate amidotransferase
pushed forward from PRPP, the molecule jus the step before via positive feedforward
During what stage of ____ synthesis does Methotrexate attack?
What vitamin does it look very similar to?
Phase III: IMP ring contstruction
Purine ring
B9, folic acid. Competative inhibitor for enzymes taht use folate
Methotrexate prevents ____ of NADPH by ___.
oxidation
DHFR
Sulfa drugs work by___.
Being a competative inhibitor for PABA, the intermeidate for folate synth.
PRPP is inhibited on both sides by ___, the end products of purine nucleotides.
IMP, AMP, GMP
Accumulation of its own endproducts inhibits its own synth.
How are the number of Gs and As balanced?
In Purine synth, AMP synth. stimulated by GTP, and vise versa GMP synth is stimulated by ATP, to ensure they’re balanced and made enough equally
Salvage pathway enzymes
HGPRT
APRT
Commited step of pyrimidine synth
Carbamoyl Phosphate Synthase II
The first step
What phase does the anticancer drug 5-fluorouracil (Adrucil) work?
phase 3: convert UMP to uridine, cytosine, thymidine deoxynucleoties
Blocks** thymidylate synthase* which stops DNA production in cancer
**two regulatory points of pyrimidine synthesis
- carbamoyl phosphate synthetates
inh. by UMP and Purines(end product), stim. by PRPP( - Aspartate transcarbamoylase (ATCase)
Feedback inh. by CTP (endproduct)
Ortic Aciduria is an issue in what phase of pyrmidine synth?
Phase 2: attach PRPP to form UMP
Issue with UMP Synthase
Buld up of Oric acid in urine, it cant be converted to UMP
Acyclovir works by resembling a guanine analogue that the virus has a higher affinity for. what happens then?
it’s helps treat herpes and chicken pox cores bc. DNA polymerase cannot use the DNA bc its a fake nucelotide
Viral supression
Purine synth happens in the ____ while pyrimidine synth happens in the ____.
cytosol
cytosol and mitochondira
enzymes needed for nucleotide degradtion
“Racing Phor New Nuceotides”
- ribonucleases and deoxyribnucleases (conver RNA/DNA to short oligomers
- Phosphodiesterases: convert short oligomers to NMPs or dNMPs
- Nucleotidases: NMPs/dNMPs to nucleosides and deoxynucleosides
- Nucleosidases: remove ribose gorup, conver to pyrimidiens, purines
AMP and GMP break down to __
Uric Acid
Allopurinol inhibits Hypoxanthine and xanthine from turning into Uric acid. These two molecules build up, yet the drug helps with Gout. How?
Uric Acid has 3 oxygens making it less water soluble, more gout causing.
Xanthine 2, and hypoxanthine have only 1 Oxygens and are more water soluble
Monosodium Urate (MSU) crystals
“disease of the wealthy” from wine and protein rich food
AMP to IMP to Inosine to ___ to Xanthine to ___
hypoxanthine
uric acid
ADA deaminase does what? what happens if its too much or too little?
adenosine homeostatis, breaks down adenosine form food
too much: hemolytic anemai, premature destruction of RBC
too little: SCID, severe combined immunodeficiency
End products of pyrimidine catabolism?
malonyl CoA
MEthylmalonyl CoA
Succinyl CoA
Pyrimidine salvage pathyway step taht acyclovir inhibits?
thymidine kinase, not dTMP production
PRPP =
phospho ribosyl pyrophosphate
Lesch Nyhan syndrom is from a default in the ___ enzyme in the ___ salvage pathway.
HGPRT
Purine
overproduction of uric acid
Committed step in purinidine synth?
First step,
Carbamoyl phosphate synthetade II
Anti cancer for pyrimidine synth?
Adrucil
Aka 5-Fluorouracil
Stops dna production
