BIOCHEMISTRY - L. Stryer - 1984

VOLUME 2

PART III. BIOSYNTHESIS OF MACROMOLECULAR PRECURSORS

CHAPTER 22. NUCLEOTIDE BIOSYNTHESIS

PROBLEMS

1. Write a balanced equation for the synthesis of PRPP from glucose via the oxidative branch of the Pentose Phosphate Pathway.

2. Write a balanced equation for the synthesis of orotate from glutamine, CO₂, and aspartate.

3. What compound serves as the activated precursor in the Synthesis of the following compounds:

a) phosphoribosylamine,

b) carbamoylaspartate,

c) orotidylate (from orotate),

d) nicotinate ribonucleotide,

e) phosphoribosylanthranilate?

4. Amidotransferases are inhibited by the glutamine analogue azaserine (O-diazoacetyl-L-Serine), an antibiotic:

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Which intermediates of Purine Biosynthesis will accumulate in Cells treated with azaserine?

5. Write a balanced equation for the synthesis of dTMP from dUMP, coupled with The conversion of serine into Glycine.

6. Bacterial growth is inhibited by sulfonamides and other related sulfa drugs. Concurrently, 5-aminoimidazole-4-carboxamide ribonucleotide accumulates. This inhibition can be reversed by The addition of p-aminobenzoate:

Propose a mechanism for the inhibitory action of sulfonamides.

7. Name the major biosynthetic reactions in which PRPP participates.

8. E. coli carbamoyl phosphate synthetase consists of a small subunit (40 kd) and a large subunit (130 kd). The purified small subunit has glutaminase activity, whereas the purified large subunit can synthesize carbamoyl phosphate from NH₃ but not from glutamine. Furthermore, the isolated small subunit exhibits ATPase activity in the presence of bicarbonate. Based on the activities of the isolated subunits, propose a likely mechanism for the reaction catalyzed by the intact enzyme.