L18: Pyrimidine nucleotide biosynthesis

Question 1

How are nucleotides provided to our cells?

Answer 1

• dietary intake of RNA and DNA
• salvage of bases: allows us to re-use purine bases by forming nucleotides; reduces the need for additional foodstuffs
• de novo synthesis: we make our own purines and pyrimidines

Question 2

Phosphoribosyl-pyrophosphate Synthetase (PRPP)

Answer 2

salvage and de novo synthesis pathways require PRPP to make nucleoside-5’-monophosphates

Question 3

Purine biosynthetic/salvage rxns utilize ___?

Answer 3

an activated sugar intermediate

Question 4

Formation of Carbamoyl-Phosphate

Answer 4

Carboxylate anion + Gln + ATP -> Carbamoyl-P

Question 5

Formation of carbamoyl-aspartate

Answer 5

Carbamoyl-P + ATCase -> [carbamoylation] -> Carbamoyl-aspartate

Question 6

Formation of Dihydroorotate

Answer 6

Carbamoyl-Aspartate (-H2O) -> dihydroorotate

Question 7

Formation of orotate

Answer 7

Dihydroorotate -> orotate

Question 8

Formation of Orotidine 5’-monophosphate (OMP)

Answer 8

Orotate (Prib-PP) -> OMP

Question 9

Formation of Uridine 5’-monophosphate (UMP)

Answer 9

OMP -> UMP

- CO2 leaves

Question 10

CTP is formed directly from ___?

Answer 10

UTP

Question 11

what are the 2 different CTP synthase isoforms?

Answer 11

Human CS-1

Human CS-2

Question 12

what is human CPS-1 essential for?

Answer 12

CDP-diacylglycerol formation

Question 13

What is Human CPS-2?

Answer 13

it is the rate-limiting enzyme in the biosynthesis of pyrimidine precursors of RNA and DNA

• it shows cooperativity in v versus [UTP] plots
• it is activated by GTP and acts to balance amounts of purine and pyrimidine nucleotides
• CS-2 deficiency affects cell growth and development

Question 14

targets for cancer chemotherapy

Answer 14

look at slide 101