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High-Yield Terms

  • Glucose-6-phosphate dehydrogenase (G6PDH): primary rate-limiting, oxidative enzyme of the PPP; mutations in this gene are the most common causes of hemolytic anemia worldwide, yet protect individuals from malaria

  • Transketolase: thiamine-requiring enzyme, enzyme of the nonoxidative stage of the PPP that transfers 2-carbon units

  • Transaldolase: thiamine-requiring enzyme, enzyme of the nonoxidative stage of the PPP that transfers 3-carbon units

  • Oxygen burst: phagocytic cells of the immune system utilize NADPH generated via the PPP to generate superoxide radicals to kill phagocytized microorganisms. This requires a dramatic increase in O2 consumption referred to as the oxygen burst

  • Chronic granulomatous disease: results in individuals harboring defects in the NADPH oxidase system of phagocytic cells, results in frequent pneumonia, abscesses of the skin, tissues, and organs, suppurative arthritis, and osteomyelitis. Defects occur in both the NADPH oxidase complex itself and the enzymes of the PPP that yield the required NADPH, particularly G6PDH


The Pentose Phosphate Pathway


The pentose phosphate pathway (PPP) (also called hexose monophosphate shunt, HMS) consists of series of interconnected reactions that serve as an alternate route for the metabolism of glucose. The pathway is primarily an anabolic pathway that utilizes the 6 carbons of glucose to generate 5-carbon sugars and reducing equivalents in the form of NADPH. However, this pathway does play a role in the oxidation of glucose and under certain conditions can completely oxidize glucose to CO2 and water. The 2 primary functions of this pathway are (1) the generation of NADPH for use in other reductive biosynthetic (anabolic) pathways and (2) to convert glucose carbons into ribose 5-phosphate (R5P) for the synthesis of the nucleotides and nucleic acids. Although not a significant function of the PPP, it can operate to metabolize dietary pentose sugars derived from the digestion of nucleic acids as well as to rearrange the carbon skeletons of dietary carbohydrates into glycolytic/gluconeogenic intermediates (Figure 15-1).

FIGURE 15-1:

Flow chart of pentose phosphate pathway and its connections with the pathway of glycolysis. The full pathway, as indicated, consists of three interconnected cycles in which glucose 6-phosphate is both substrate and end product. The reactions above the broken line are nonreversible, whereas all reactions under that line are freely reversible apart from that catalyzed by fructose 1,6-bisphosphatase. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Harper's Illustrated Biochemistry, 29th ed. New York, NY: McGraw-Hill; 2012.

Graphic Jump Location

Enzymes that function primarily in the reductive direction utilize the NADP+/NADPH cofactor pair as cofactors as opposed to oxidative enzymes that utilize the NAD+/NADH cofactor pair. The reactions of fatty acid biosynthesis and steroid biosynthesis utilize large amounts of NADPH. As a consequence, cells of the liver, adipose tissue, adrenal cortex, testis, and lactating mammary gland have high levels of the PPP enzymes. In fact 30% of ...

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