Pyrimidines

What are some examples of pyrimidines?

- uracil

- uridine

- cytosine

- cytidine

De novo synthesis of pyrimidine is produced in what 2 areas?

- cytosol

- mitochondria

What is the enzyme complex used in the de novo synthesis of pyrimidine?

C: carbamoyl-phosphate synthetase

A: aspartate transcarbamoylase

D: dihydroorotase

What is the first step of the de novo synthesis of pyrimidine?

Carbon dioxide, glutamine, ATP + carbamoyl phosphate synthetase II --> carbamoylphosphate

What is the rate limiting enzyme of the de novo synthesis of pyrimidine?

aspartate carbamoyl transferase

Dihydroorotase produces ______?

dihydroorotate

Dihydroorotate produces orotate by what enzyme?

dihydroorotate dehydrogenase

Dihydroorotase dehydrogenase is bound to...?

inner mitochondrial membrane

What 2 drugs inhibits dihydroorotase dehydrogenase?

- leflunomide

- teriflunomide

Orotate + PRPP produces _____?

OMP (orotidine monophosphate)

Ribonucleotides --> deoxyribonucleotides uses what enzyme?

ribonucleoside diphosphate reductase

What inhibits ribonucleodie diphosphate reductase?

- gemcitabine

- hydroxyurea

- fludarabine

dUMP --> dTMP uses what enzyme?

thymidylate synthase

Methotrexate inhibits _____?

dihydrofolate reductase (DHFR)

5-fluro uracil (5-FU) inhibits ______?

thymidylate synthase (inhibits DNA synthesis)

What is the salvage pathway of pyrimidine?

nucleosides & free bases generated by DNA & RNA breakdown are converted back to nucleotide monophosphates

Uridine is converted to _____?

UMP

Cytidine is converted to _____?

CMP

Deoxythymidine is converted to _____?

TMP

Deoxycytidine is converted to _____?

dCMP

Deficiency of both orotate phosphoribosyltransferase & orotidylate decarboxylase is what disease?

Type I orotic aciduria

Deficiency of only orotidylate decarboxylase is what disease?

Type II orotic acuduria

What are the complications of orotic aciduria?

- anemia

- developmental delay

- impairment of growth & cognition

Catabolism (degradation) of pyrimidine forms highly water-soluable products like what?

- CO2

- NH3

- Uracil (b-alanine)

- Thymine (b-aminoisobutyrate)

B-hydroxybutyric aciduria is due to a deficiency of ______?

dihydropyrimidine dehydrogenase

What are the complications of B-hydroxybutyric aciduria?

- seizures

- microcephaly

- hypertonia

- delayed development

- intellectual disability

- autism