Question

Hi Everyone,

This is a biochemistry homework problem, I really don't understand some of the questions. Any help is greatly appreciated. Thank you!

3. Draw an the mechanism showing how the glutamine-PRPP amidotransferase adds nitrogen to PRPP in the first comitted step of purine nucleotide biosynthesis. Compare this reaction with the addition of orotate to PRPP in the 5th step of purine biosynthesis.

Answer 1

Given below is the detailed enzymatic mechanism of addition of nitogen to PRPP by glutamine-PRPP amidotransferase

First Ammonia is generated in glutaminase domain active site of an enzyme:

U2N că Gin 102 HN, con Glyoz | >_< on 5 Asn lol Asniol CI Asnool "100 R ol Cysa 27 Alyaz lov H₂NL02 My My Co NM₂] Glyl02 WN 1. Ho (5"-NR Asmiol Sri Ashio

The generated ammonia is used in reaction given below by replacing pyrophosphate in PRPP and thus led to formation of phosphoribosylamine:

Tyres и ти Tur 258 OY D.O. UzNja... OPO U₂N DOPO2- ang -04 : ио "ои on sing no on 5-Phisbhoubisul amine O=P-6--Myat PRPP (s' phosphoribuspl- 1-byrophosphate)

Comparison of addition of Nitrogen to PRPP by Glutamine-PRPP amidotransfersae with addition of orotate to PRPP in the 5th step of Purine biosynthesis

Glutamoll Glutamate 20 pou tud o ( 2-0, pouze Hop-o-p-o Glulamaté- PRPP amido transfrase ou ou cu o tome 51-phosphorbosy) 1 pyrophosphate (PIPP) ou 5. Phosphoribusylamine

2-0₂ POH₂C z Plit 2-0 POHRC O O NI 2 + Ho on -I no on Orotate 5- Phosphoribosyl-1-pyrophosphate Oroticylate

In the addition reaction of Nitrogen to PRPP by Glutamine-PRPP amidotransfersae, Pyrrophosphate at C1 position is replaced by Ammonia (i.e. Ammonia is added to C1 position of ribose). Whereas, in the addition reaction of orotate to PRPP, Pyrophosphate is replaced by orotate at C1 position. Therefore addition reaction in both reaction occurs at same position of ribose moeity.