Regulation Of Pyrimidine Nucleotide Biosynthesis

Gene Expression & Enzyme Activity Both Are Regulated

The activities of the first and second enzymes of pyrimidine nucleotide biosynthesis are controlled by allosteric

CDP-

GDP-

Figure 34-6. Regulation of the reduction of purine and pyrimidine ribonucleotides to their respective 2'-deoxyribonucleotides. Solid lines represent chemical flow. Broken lines show negative (©) or positive (©) feedback regulation.

CARBAMOYL PHOSPHATE SYNTHASE II

5CH2

ASPARTATE TRANSCAR-BAMOYLASE

Carbamoyl phosphate (CAP)

Aspartic acid

Carbamoyl aspartic acid (CAA)

DIHYDRO-OROTASE

DIHYDROOROTATE DEHYDROGENASE

XH2 2

COO-

Dihydroorotic acid (DHOA)

CO2 + Glutamine + ATP

HN3 4 5H

OROTIDYLIC ACID DECARBOXYLASE

PPi PRPP

OROTATE PHOSPHORIBOSYL-TRANSFERASE

- dUDP (deoxyuridine diphosphate)

RIBONUCLEOTIDE REDUCTASE

dUMP

CTP SYNTHASE

- Glutamine

THYMIDYLATE SYNTHASE

- N5,N1°-Methylene H4 folate

Orotic acid (OA)

Figure 34-7. The biosynthetic pathway for pyrimidine nucleotides.

H2 folate

regulation. Carbamoyl phosphate synthase II (reaction 1, Figure 34-7) is inhibited by UTP and purine nucleotides but activated by PRPP. Aspartate transcar-bamoylase (reaction 2, Figure 34-7) is inhibited by CTP but activated by ATP. In addition, the first three and the last two enzymes of the pathway are regulated by coordinate repression and derepression.

Purine & Pyrimidine Nucleotide Biosynthesis Are Coordinately Regulated

Purine and pyrimidine biosynthesis parallel one another mole for mole, suggesting coordinated control of their biosynthesis. Several sites of cross-regulation characterize purine and pyrimidine nucleotide biosynthesis. The PRPP synthase reaction (reaction 1, Figure 34-2), which forms a precursor essential for both processes, is feedback-inhibited by both purine and pyrimidine nucleotides.

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