7: Pentose Phosphate Pathway (PPP), Purine and Pyrimidine Metabolism

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Learning objectives

Describe the role of NADPH produced by the pentose phosphate pathway in metabolism and regulation of glucose 6-phosphate dehydrogenase.
Determine the utility of the oxidative and nonoxidative portions of the pentose phosphate pathway (PPP) and how these pathways interface with glycolysis.
Describe the amino acid composition of glutathione (GSH) and understand the role of GSH in attenuating oxidative damage.
Describe how the pentose phosphate pathway and the process of DNA replication interface with the biosynthesis of purine and pyrimidine nucleotides.
Evaluate the central role of 5-phosphoribosyl-1-pyrophosphate (PRPP) in nucleotide metabolism.
Describe the purine salvage pathway, specifically the reaction catalyzed by hypoxanthine-guanine phosphoribosyltransferase (HGPRT).
Identify the key regulatory steps in both purine and pyrimidine synthesis, and evaluate flux through each pathway depending on levels of allosteric activators and inhibitors.
Describe conditions that lead to elevated orotic acid, and interpret urine orotic acid concentration for the diagnosis of defects of the urea cycle or pyrimidine biosynthesis.

As we have seen previously, glucose can be diverted to several different pathways depending on metabolic needs. One of these pathways is the pentose phosphate pathway, which plays an integral role in producing both NADPH and the five-carbon sugar ribose. NADPH provides the cell with an energy source for reductive biosynthesis and detoxification of free radicals, while ribose is an essential component in the synthesis of both purine and pyrimidine nucleotides. Aberrations (increases or decreases) in either of these metabolic pathways, PPP or nucleotide synthesis, can result in the common clinical presentations of anemia, jaundice, or gout.

Thumbnail: Grey, Kindred, Chapter 7. 2021. Chemical structure by Henry Jakubowski. CC BY 4.0.