Pyrimidines

What are the three components of a nucleotide

Nitrogenous base (pyrimidine/purine) , pentose, 1+ phosphate

Name: Adenine in DNA and RNA

Base Type: Purine

Double ring

Name: Guanine DNA and RNA

Base Class: Purines

Double Ring structure

Name: Cytosine DNA and RNA

Base Type: Pyrimidine

Single ring structure

Name: Thymine

Base Type: Pyrimidines

Single ring structure

Name: Uracil

Base Type: Pyrimidines

Single ring structure

Dietary DNA and RNA

ingested nucleic acids are degraded through sequential action of nucleases

de novo pathways

-bases are synthesized while attached to ribose

-pyrimidine ring is synthesized as orotate

-gly is the precursor for purines

-asp is the precursor for pyrimidines

-amino acids, ribose-5-phosphate, co2, nh3

salvage pathway

recycle the free bases and nucleotides released from nucleic acid breakdown

Phosphoribosyl-pyrophosphate (PRPP)

activated ribose sugar ring and base

made from ribose 5-phosphate + ATP converted to PRPP and AMP

Pyrimidine Biosynthesis Pathway

-ribose 5-phosphate attached after pyrimidine ring formation

-aspartate and carbamoyl phosphate provides atoms for ring structure

CPS 2

-Makes carbamoyl phosphate needed in pyrimidine biosynthesis

-in cytosol

-uses a transfer tunnel to move ammonia from glutamine to biosynthetic site

-tunnel prevents protonation of ammonia and allows carbamate to be transferred carbamoyl phosphate

Explain carbamoyl pools

Same metabolite (carbamoyl phosphate) is used for different purposes: The Urea Cycle and nucleotide synthesis

Which enzyme makes N-carbamoyl aspartate? What does it require? What inhibits it

Aspartate trans-carbamoylase

It’s high regulated and require carbamoyl phosphate and aspartate

It’s inhibited by CTP

What makes L-dihydroorotate?

-Dihydroorotase

-Dehydration reaction (removes H2O) to close ring

What makes orotate

-Enzyme: Dihydroorotate dehydrogenase

-Reduces NAD+ to NADH

What forms orotidylaye? How?

-enzyme: orotate phosphoribosyl transferase

-add phosphate and sugar

-amine of ring attacks PRPP

-what’s required: PRPP

Name the structure

OMP (Orotidylate 5’ monophosphate)

Describe the formation of UTP

1) OMP is decarboxylated to UMP (uridylate) by orotidylate decarboxylase

2) UMP is phosphorylated to UTP by kinases

3) UTP is converted to CTP by cytidylate synthetase using glutamine and ATP

Describe formation of TMP

-Enzyme: Thymidylate synthase converts dUMP to dTMP by transferring a methylene group from N5,N10 Methylene tetrahydrofolate

-Dihydrofolate reductase reduces dihydrofolate to tetrahydrofolate

Describe regulation of the CAD complex

Enzymes: CPS2, Aspartate Transcarbamoylase (ATCase), Dihydroxyorotase

• CPS2 and transcarbamoylase is inhibited by UTP and activated by PRPP

What activates CTP Synthetase to form UTP?

-GTP (a purine) which balances the amount of C/G

What does catabolism of pyrimidines lead to?

NH4+ production and urea synthesis

What are carbons of thymine degraded to?

Succinyl-CoA

What are carbons of cytosine and uracil degraded to?

Acetyl-CoA