Purines and pyrimadines Flashcards
what do we need to make purines
THF
GLYCINE (major difference)
ASPARTATE
Glutamine
what do we need purines for ?
energy carrier molecules
SAM
DNA synthesis
what are the precursor molecules for purines and pyrimides
purines: IMP - the first purine
pyrimidines; OMP - the first pyrimidie
what is the commited step for purine synthesis
The enzyme glutamin prpp amindotransferase
what are the steps after formation of 5 phosophoriboysul 1 amine
- Glycine +atp
- N-formyl THF - THF
- Glutmine +ATP
- ATP
- CO2
- Aspartate+ATP
- Fumerate (leaving)
- Nformyl THF
- removal of water
IMP
draw the pathway from IMP TO AMP AND GMP and name the 4 enzymes involved
- To form AMP
- adenylosuccinate synthetase (GTP)
- adenylosuccinate lyase (removes fumerate) - To form GMP
- IMP DH (nad, h20)
- XMP- Glutamine amidotransferase (atp)
where does the breakdown and synthesis of purines occure
breakdown: extrahepatic tissues
synthesis : liver
where does the breakdown and synthesis of purines occur
breakdown: extrahepatic tissues
synthesis : liver
describe the salvage pathway of purines
AMP- ADENOSINE- INOSINE-HYPOXANTHINE ( 2 paths)
1.gout 2. recycling goes to IMP then back to AMP
GMP-guanosine-guanine - GMP ( vie HGPRT)
Describe process of forming deoxyribose
happens at the nucleotide diphosphate level , the enzyme is ribonucleotide reductase which has thioreduxin as a cofactor (sh) that gets oxidised. but needs to be replaced to keep the cycle going so another enzyme thioreduxin reductase which uses NADPH .
same example with glutathione
regulation of ribonucleotide reductase
quite complex as enzyme has 2 allosteric sites
ATP- bound to active site (activates)
dATP (deactivates)
starts of with the pyrimides (C+U)
C: CDP-dCDP - dCTP—–dna synthesis
U: UDP-dUDP-dUMP-dTMP-dTDP-dTTP- dna synthesis
the dttp goes and binds to regulatory site and now activates the purines
GDP-dGDP-dGTP-dna
ADP-dADP-dATP-dna (inactives enzyme)
what enzyme abnormailites can cause goat/podogra
- HGPRT
- PRPP sytnthesase ( cos usually its negatively controleed by adp and gdp but in variant forms can lead to an overproduction of purines)
Lesch-Nyan synchdrome
mental retardation, purine salvage aint working , hyerourecemia
X LINKED
self mutalation
disorder of nervous sytem
clincial aspects of purine metabolism
usually results from abnormal purine break down
HGPRT -complet lack = lesh nyan syndrome
HGPRT- partial defect- GOUT
ADA- complet defct - SCID
Glucose 6 phosphatase - von Gierkes disease - hyperurecemia
Xanthine oxidase- xanthinuria - hypourecima - renal lithiasis (stones)
APRT- renal lithiasis
MANY DEFCTECT IN PRPP SYNTHESTASE
- over active because of elevated vmax
- does not respond to feedback loop
- no feedback loop produced
- has an increased affinity for substrate (ribose 5 phosphate)
origin of pyrimidine ring
- majority (aspartate)
- glutamate
- co2
name the products and enzymes of de novo synthesis of pyrimidines
- Carbomoyl phopsphate
- ATtcase gives us carbomoyl aspartate
- dihydrorotase gives us DHOA
- dihydroorat DH gives us orotic acid
- orotate phosphribosyl transferase gives us OMP
- Orotodylic acid decarboxylase
what are the products that can be formed from UMP
UMP-UDP-dUDP-dUMP-dTMP-dTDP-dTTP
OR
UMP——2 kinases——UTP—atp + glutamine -CTP
thymidylate synthase
coverts DUMP —-dTMP
highly regulated
requires THF to work
Thymidylate synthase
coverts DUMP —-dTMP
highly regulated
requires THF to work
how do we regenerate THF after it has been used
THF gets turned into DHF which then gets coverted back by dihydrofolate reductase w which uses NADPH
regulation of Atcase
:) ATP
;( CTP
Which pathways uses the slavage pathway more and why?
purine- about 90~% compared to 30% of pyrimide this is because in pyrimidine we have low numbers of ribose 1 phosphate and deoxy ribose 1 phosphate
thymidine kinase
enzyme that adds ATP to thymidine to give you dTMP. It is allosterically inhibited by dTTP. Activity of TK is closely related to the proliferative state of the cell. TK activity tises dramatically as celll enters S phase
what other products aprart from the slavage pathay can pyrimides form, step by step
Catbabolism:
cytosine - deaminated - uracil - b alanine- acetyl coa
thymine - b aminoisobutyrate- succinyl co A
products are excreted in urine or are converted to water and co2 and Nh3
clinical aspects of pyrimidines
UMP synthase is made up of the last 2 enzymes
- orotate phosphoribosyl transferase
- OMP decarboxylase
orotic aciduria type 1 : deficiency of both
orotic aciduria type 1: deficiency of last enzyme
symptoms:
- retarded growth
- leukopenia
- severe anemia
treatment: oral intake of uridine or cytidine because then they will be convertred to UMP by the acition of kinase
Mild orotic aciduria:
increases levels of CP which increases pyrimidine synthesis
deficiency of Vitamin B12 and folic acid
-deficiency of dTMP
which type of THF is used to give a methyl group to dUMP
methylenetetrahydrofolate
