Page 80 - First Aid for the USMLE Step 1 2020, Thirtieth edition [MedicalBooksVN.com]_Neat

36 SECTION II BIOCHEmISTRY ``BIOCHEMISTRY—MOlECUlAR BIOCHEmISTRY ``BIOCHEMISTRY—MOlECUlAR

De novo pyrimidine Various immunosuppressive, antineoplastic, and antibiotic drugs function by interfering with
and purine synthesis nucleotide synthesis:
Pyrimidine synthesis:
Pyrimidine base production Purine base production or
(requires aspartate) Ribose 5-P reuse from salvage pathway ƒ Leflunomide: inhibits dihydroorotate
(de novo requires aspartate, dehydrogenase
Glutamine + CO
2 glycine, glutamine, and THF) ƒ 5-fluorouracil (5-FU) and its prodrug
2 ATP CPS2 (carbamoyl
phosphate capecitabine: form 5-F-dUMP, which inhibits
2 ADP + P + synthetase II) PRPP (phosphoribosyl thymidylate synthase ( dTMP)
i
Glutamate pyrophosphate) synthetase
Purine synthesis:
Carbamoyl ƒ 6-mercaptopurine (6-MP) and its prodrug
phosphate
Aspartate azathioprine: inhibit de novo purine synthesis
Leflunomide ƒ Mycophenolate and ribavirin: inhibit inosine
PRPP 6-MP,
Orotic azathioprine monophosphate dehydrogenase
acid
Purine and pyrimidine synthesis:
UMP synthase UMP Mycophenolate, ƒ Hydroxyurea: inhibits ribonucleotide
(impaired in IMP ribavirin
orotic aciduria) UDP reductase
Ribonucleotide reductase and pyrimethamine: inhibit dihydrofolate
Hydroxyurea AMP GMP ƒ Methotrexate (MTX), trimethoprim (TMP),
dUDP CTP reductase ( deoxythymidine monophosphate
[dTMP]) in humans, bacteria, and protozoa,
N N - dUMP respectively
5 10
methylene THF
THF Thymidylate synthase 5-FU,
DHF capecitabine CPS1 = m1tochondria (urea cycle)
Dihydrofolate
reductase dTMP CPS2 = cyTWOsol
MTX, TMP,
pyrimethamine

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