Question

Certain glutamine analogs irreversibly inactivate enzymes that bind glutamine. Identify the nucleotide biosynthetic intermediates (and the enzymes that catalyze the reactions that utilize them) that accumulate in the presence of those compounds. For a given pathway, list your answers in the order of the reactions involved.

Answer 1

5-phosphoribosyl-1-pyrophosphate to accumulate, PRPP will accumulate due to the inactivation of the enzyme glutamine-PRPP amidotransferase

Formylglycinamide ribonucleotide (FGAR) will accumulate due to inactivation of the enzyme formylglycinamide ribonucleotide amino transferase.

Xanthylate (XMP) will accumulates because of the inactivation of the GMP synthetase reaction.

Uridine 5'triphosphate (UTP), a nucleotide biosynthetic product as well as an intermediatein the synthesis ofCytidine 5'triphosphate will accumulate due to the inactivation of cytidylate synthetase.

Step-by-step explanation:

The biosynthesis of nucleotides occurs by means of two pathways: the de novo pathways and the salvage pathways.

The de novo pathways of the synthesis of nucleotides begins with their metabolic precursors which include amino acids, ribose-5-phosphate, carbon (iv) oxide and ammonia.

The salvage pathways reuse the free bases and nucleotides from the breakdown of nucleic acids.

Glutamine analogs that irreversibly inactivate enzymes that bind glutamine will cause accumulation of intermediates in the nucleotide biosynthetic pathways.

Glutamine is used as the amino group donor in the first committed step of de novo synthesis of purine nucleotides. In this step, 5-phosphoribosyl-1-pyrophosphate, (PRPP) is converted to 5-phosphoribosylamine using the amino group of glutamine by the enzyme glutamine-PRPP amidotransferase. Inactivation of this enzyme will cause 5-phosphoribosyl-1-pyrophosphate to accumulate.

In the fourth step of the de novo synthesis of purine nucleotides, inactivation of the enzyme formylglycinamide ribonucleotide amino transferase will cause formylglycinamide ribonucleotide (FGAR) to accumulate.

In the biosynthesis of guanylate from Inosinate, the intermediate xanthylate (XMP) will accumulate due to inactivation of the enzyme xanthylate-glutamine amidotransferase.

In the de novo synthesis of pyrimidine nucleotides, Uridine 5'triphosphate (UTP), a nucleotide biosynthetic oroduct as well as an intermediate of Cytidine 5'triphosphate will accumulate due to the inactivation of cytidylate synthetase.

Carbamoyl phosphate is synthesized by the enzyme carbamoyl phosphate synthetase II using glutamine and bicarbonate and two ATP molecules. However, the other substrates of this enzyme do not accumulate.