Quais são as Purines e as bases ?
Guanosine - base Guanine
Adenosine - base Adenine
Inosine- base Hypoxanthine
Compostas por 2 rings, phosphate and pentose ( sugar)
Nomes vão variar de acordo com o número de phosphate
Ex:
AMP : adenosine mono phophate
ATP: adenosine tri phosphate
Purine carbon donors
CO2
Glycine
THF - B9
Purine Nitrogen DONORS
Glutamine
Aspartate
Glycine
Purine syntheses de novo
- came from zero
- HMP shunt ➡️ribose 5 -P➡️PRPP
PRPP ( * enz: glutamine PRPP amidotransferase ) ➡️ IMP
O IMP segue para tres caminhos
1)➡️AMP ➡️ adenine
2)*enz: IMP dehydrogenase ➡️GMP ➡️ guanine
3)➡️hypoxanthine
enz: IMP dehydrogenase pode ser inibida por :
RIBAVARIN
MYCOPHENOLATO
Purine SALVAGE
-Mechanism to recycle
Hypoxanthine , guanine and adenine to make more purine
- todas as bases se conectarao a PRPP e gerarão nucleotides
Hypoxanthine + PRPP= IMP *
Guanine + PRPP=GMP* enz HGPRT
Adenine + PRPP =AMP * enz APRT
Obs: 6 mercaptopurine compete com Hypoxanthine e guanine pelo PRPP
redução de RNA E DNA.
OBS: HGPRT - lesch Nyhan syndrome
Purine BREAKDOWN
- excreção das purinas
- 2 formas:
1) Hypoxanthine and Guanine ➡️ xantine ➡️ (* enz xantine oxidase) ➡️ac úrico
2) adenine ➡️ AMP ➡️ adenosine ➡️
*enz: adenosine deaminase ➡️ IMP ➡️ Hypoxanthine e segue igual n 1
Obs def de adenosine deaminase
Leads to severe imunodeficiency
Obs: alopurinol inibe xantine oxidase
Reduz ácido úrico
Lesch Nyhan Syndrome
- X LINKED
- def HGPRT
- ⬆️ Hypoxanthine
- ⬆️ guanine
- desviados para breakdown ⬆️ ac úrico
Paciente com gota juvenil, mta dor
Automutilação , corea
Pyramidine carbon and nitrogen donors
Are the same
Aspartate
Carbamoyl - P
Pyrimidine metabolism
Glutamine ➡️ * enz carbamoyl synthetase II ➡️ carbamoyl P ➡️
➡️ orotic acid
Orotic acid ➡️ * enz UMP synthetase ➡️ Adiciona PRPP ➡️ UMP
UMP SEGUE 2 caminhos :
1) UDP ➡️ dUDP ➡️ d UMP ➡️ * enz thymidylate ➡️ d TMP
Thimidine so existe em DNA
FORMATO d TMP
2) UTP ➡️ CTP
Cytarabine : quimioterápico ( ARA C)
Imita o CTP no DNA porém eh disfuncional , reduz DNA SYNTHESES E provoca morte celular
Quais são as pyrimidinas e as bases?
Thimidine - base thymine
Cytidine- base cytosine
Uridine - uracil
Thimidine - just used in DNA
FORM d TMP
d TMP SYNTHESIS
Pyrimidine cycle
d UMP ➡️➡️➡️➡️ dTMP
Enz: thymidylate synthase
This enzyme needs cofactor
N5, N10- THF ( forma ativa ) , doa metil e se torna DHF ( folate B9 tb doa DHF para o cycle, atenção para deficiência de folate )
DHF ➡️➡️➡️➡️ THF
Enz dihydroxyfolate reductase
( inibida pelo methotrexate trimethoprim )
THF ➡️➡️➡️➡️ N5 N10 THF
parte da forma ativa N5 N10 THF desvia para forma de reserva - N5 methylTHF
Forma reserva retorna ao ciclo para permitir a fabricacao de DNA
N5 methylTHF ➡️➡️➡️ THF
COFACTOR B12
( atenção para deficiência de B12)
Lembrar dos influenciadores do cicko:
B9, metrotexato, B12
