De novo purine 1 (23)

What is the de novo pathway?

Synthesis of nt from starting materials + highly conserved

What are those starting materials?

AAs, rbose and CO₂

What are the 2 de novo pathways?

1. Purine pathway

2. Pyrimidine pathway

What is the outcome of the purine pathway?

Inosine monophosphate or IMP

What is the outcome of the pyrimidine pathway?

Uridine monophosphate or UMP

What structure(s) corresponds to the base?

Aromatic ring

What structure(s) correspond to the nucleoside?

Base + sugar

What structure(s) correspond to the nucleotide?

Base+sugar+Phosphate group

What does the base look like for purines?

6 membered ring + 5 membered ring

What does the base look like for pyrimidines?

6 membered ring

On which ring number are the Nitrogen atoms located on purine bases?

1,3,7 and 9

On which ring number are the Nitrogen atoms located on pyrimidine bases?

1 and 3

On which nitrogen atom is the link to ribose located for both pathways?

1. Purine = N9

2. Pyrimidine = N1

What are the 2 types of sugars?

Ribose and Deoxyribose

What’s the difference between them and what does it mean?

C2 group -OH→-H = RNA→DNA

What are the 3 nucleotides found in both DNA and RNA?

1. Adenylate (AMP)

2. Guanylate (GMP)

3. Cytidylate (CMP)

What is the nucleotide that is only found in RNA?

Uridylate (UMP)

What nucleotide is ony found in DNA?

Deoxythymidylate (dTMP)

What are the nucleotide linkages observed in RNA?

A+U and G+C

What base is this?

Hypoxanthine

What base is this?

Xanthine

What base is this?

Orotate

What base is this?

Uric acid

What nucleotides does the purine pathway yield?

A + G

What nucleotides does the pyrimidine pathway yield?

C + U + T

What’s the difference between caffeine and theobromine?

Caffeine N3 = -CH3 whereas Theobromine N3 = -H

Differences between dideoxycytidine and AZT (2)

1. Cytosine vs Thymine base

2. C3 = -H vs C3 = N₃^-

What other types of molecules are made from the purine pathway?

Cofactors, vitamins and signalling molecules

What is the preferred structure of oral drugs and why?

Base or nucleosides, rarely nucleotides BC the phosphates get hydrolyzed by our gut

What is surprising about tRNA modification?

Up to a quarter of it is modified

How are the nucleotides assembled in the purine pathway?

Sugar → Add phosphate groups → Add base

Step #1 of purine pathway

R5P + ATP → PRPP + AMP

What does that first step entail?

1. Addition of 2 PO3^3-

2. Complex regulation

What can be the source of phosphate?

ATP or GTP

Step #2 of purine pathway

PRPP + Glutamine → Phosphoribosylamine + PP_i

What does this 2nd step entail?

1. Anomeric inversion = beta sugar anomer

2. Site of purine specific regulation

Which of these steps is the committing step?

Step #2

What are the 2 nitrogen donors?

1. Glutamine: from the sidechain

2. Aspartate: from the backbone