L33- Pyrimidine Metabolism Flashcards
The first step in pyrimidine synthesis is the synthesis of carbamoyl phosphate in the cytoplasm. What is the enzyme that catalyzes this step?
Carbamoyl phosphate synthetase II (CPSII); not to be confused with CPS I which is in the mitochondria and involved in the urea cycle!
Which three enzymes are domains of the same protein that yields dihydroorotate?
CPS II, aspartate transcarbamoylase and dihydroorotase.
Which enzyme oxidizes dihydroorotate to orotate?
Dihydroorotate dehydrogenase.
What reaction is catalyzed by orotate phosphoribosyltransferase (OPRT)?
Condensation of orotate with PRPP to form orotidine-5-phosphate (OMP).
Which enzyme generates UMP from OMP?
OMP decarboxylase.
Deficiency of which enzyme(s) can lead to orotic aciduria?
The bifunctional protein that consists of both orotate phosphoribosyltransferase (OPRT) and OMP decarboxylase. Orotic aciduria can also be secondary to urea cycle enzyme deficiencies, like ornithine transcarbamylase (OTC) in particular.
Which molecule is produced when the amide nitrogen from glutamine is transfered to the C4 of the UTP pyrimidine ring?
CTP.
What class of enzyme is thought to be involved in pyrimidine synthesis via the salvage pathway?
The pyrimidine nucleoside kinases.
What is the end product of the catabolism of uracil?
Beta-alanine.
What is the end product of the catabolism of thymine?
Beta-aminoisobutyrate.
True or False. Unlike purine catabolism, pyrimidine catabolism occurs in the liver, yields soluble end products, and the pyrimidine rings are opened.
True.
Which enzyme converts ribonucleosides disphosphates into deoxyribonucleoside diphosphates?
Ribonucleotide reductase.
What is the function of the small protein thioredoxin?
It is the electron donor in the reaction catalyzed by ribonucleotide reductase. In other words, it reduces ribonucleoside diphosphates to deoxyribonucleoside diphosphates.
Which enzyme regenerates the reduced form of thioredoxin?
Thioredoxin reductase.
What is the cofactor for the reaction catalyzed by thioredoxin reductase?
FAD.
Which enzyme is inhibited by hydroxyurea?
Ribonucleotide reductase.
What is the product of dUMP methylation?
TMP.
Which enzyme methylates dUMP to form TMP?
Thymidylate synthase.
What is the carbon donor in the methylation of dUMP to produce TMP?
N5, N10 - methylene tetrahydrofolate.
Formation of TMP from dUMP oxidizes tetrahydrofolate to dihydrofolate. What enzyme regenerates tetrahydrofolate?
Dihydrofolate reductase.
What is the main regulatory site of de novo pyrimidine synthesis?
The carbamoyl phosphate synthetase II (CPS II) reaction.
What are the activators and inhibitors of carbamoyl phosphate synthetase (CPS II)?
CPS II is stimulated by PRPP and ATP, and inhibited by UTP.
What are the activators and inhibitors of OMP-decarboxylase?
OMP-decarboxylase is inhibited by UMP and indirectly stimulated by PRPP.
Which pyrimidine synthesis metabolite accumulates when OMP-decarboxylase is inhibited?
Orotate (not OMP). This is because orotate phosphoribosyltransferase (OPRT) and OMP-decarboxylase are located on the same polypeptide.
