Week 15: Purine and Pyrimidine Synthesis

Purine biosynthesis starts with the activation of a 5-carbon sugar. In this initial reaction, ribose 5-phosphate is converted into which of the following compounds?
- 5- methyl thymidine
- Inosine monophosphate
- Glucose 6-phosphate
- 5- phosphoribosyl pyrophosphate (PRPP)
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Purine biosynthesis starts with the activation of a 5-carbon sugar. In this initial reaction, ribose 5-phosphate is converted into which of the following compounds?
- 5- methyl thymidine
- Inosine monophosphate
- Glucose 6-phosphate
- 5- phosphoribosyl pyrophosphate (PRPP)
- 5- phosphoribosyl pyrophosphate (PRPP)

PRPP is the active sugar needed for nucleotide synthesis.
Increased flux through which of the following pathways will increase the synthesis of purines and pyrimidines?
- Pentose phosphate pathway
- Ketogenesis
- Fatty acid synthesis
- Glycogen synthesis
- Pentose phosphate pathway

Indicate the regulatory role of phosphoribosyl pyrophosphate (PRPP) in hepatic purine biosynthesis and the specific reaction of hepatic purine biosynthesis that is feedback inhibited by AMP and GMP.
Which of the following enzymes is used directly in the synthesis of dTMP (thymidine)?
- Aspartate transcarbamoylase
- Thymidylate synthase
- Dihydrooratase
- Carbamoyl phosphate synthetase II (CPSII)
- Thymidylate synthase

Compare and contrast the roles of dietary nucleic acids and of de novo biosynthesis in the production of purines and pyrimidines destined for polynucleotide biosynthesis, including the reaction by phosphoribosyl 1-pyrophosphate synthetase.
Synthesis of which of the following nucleotides does not require folate?
- CTP
- dTTP
- GTP
- ATP
- CTP

Identify the reactions discussed that are inhibited by anticancer drugs.
Which of the following compounds contributes both the sugar and phosphate groups to the nucleotide bases?
- 5- methyl thymidine
- Inosine monophosphate
- Glucose 6-phosphate
- PRPP (5- phosphoribosylpyrophosphate)
- PRPP (5- phosphoribosylpyrophosphate)

Compare and contrast the roles of dietary nucleic acids and of de novo biosynthesis in the production of purines and pyrimidines destined for polynucleotide biosynthesis, including the reaction by phosphoribosyl 1-pyrophosphate synthetase.
A newborn is suspected of a defect in nucleotide synthesis due to the elevation of orotic acid. It is determined there is no deficiency in orotate phosphoribosyltransferase. Based on this presentation, which of the following enzymes is most likely deficient?
- Carbamoyl phosphate synthetase II (CPSII)
- Thymidylate synthase
- Ornithine transcarbamylase
- Glutamyl amidotransferase
- Ornithine transcarbamylase

Identify reactions whose impairment leads to modified pathologic signs and symptoms. Indicate why there are few clinically significant disorders of pyrimidine catabolism.
A 40-year-old male comes into the doctor's office with severe pain in his big toe. He is diagnosed with gout. Allopurinol is administered and this drug will inhibit which of the following enzymes?
- Xanthine Oxidase
- Adenosine deaminase
- Adenine phosphoribosyltransferase
- Thymidine kinase
- Xanthine Oxidase

Write the structure of the end product of purine catabolism. Comment on its solubility and indicate its role in gout, Lesch-Nyhan syndrome, and von Gierke disease.
Which of the following is the common intermediate for pyrimidine synthesis?
- Uridine monophosphate (UMP)
- Hypoxanthine
- Cytidine monophosphate (CMP
- Inosine monophosphate (IMP)
- Uridine monophosphate (UMP)

Identify reactions whose impairment leads to modified pathologic signs and symptoms. Indicate why there are few clinically significant disorders of pyrimidine catabolism.