B. Ribulose 5-phosphate formation 6-Phosphogluconolactone is hydrolyzed by 6-phosphogluconolactone hydrolase in the second step. The oxidative decarboxylation of the product, 6-phosphogluconate, is catalyzed by 6-phosphogluconate dehydrogenase. This third irreversible step produces ribulose 5-phosphate (a pentose sugar– phosphate), CO2 (from carbon 1 of glucose), and a second molecule of
NADPH (see Fig. 13.2).
III. REVERSIBLE NONOXIDATIVE REACTIONS
The nonoxidative reactions of the pentose phosphate pathway occur in all cell types synthesizing nucleotides and nucleic acids. These reactions catalyze the interconversion of sugars containing three to seven carbons (see Fig. 13.2). These reversible reactions permit ribulose 5-phosphate (produced by the oxidative portion of the pathway) to be converted either to ribose 5-phosphate (needed for nucleotide synthesis; see p. 293) or to intermediates of glycolysis (that is, fructose 6-phosphate and glyceraldehyde 3-phosphate). For example, many cells that carry out reductive biosynthetic reactions have a greater need for NADPH than for ribose 5-phosphate. In this case, transketolase (which transfers two-carbon units in a thiamine pyrophosphate [TPP]-requiring reaction) and transaldolase (which transfers three-carbon units) convert the ribulose 5phosphate produced as an end product of the oxidative phase to glyceraldehyde 3-phosphate and fructose 6-phosphate, which are glycolytic intermediates. In contrast, when the demand for ribose for nucleotides and nucleic acids is greater than the need for NADPH, the nonoxidative reactions can provide the ribose 5phosphate from glyceraldehyde 3-phosphate and fructose 6-phosphate in the absence of the oxidative steps (Fig. 13.3).
In addition to transketolase, TPP is required by the multienzyme complexes pyruvate dehydrogenase (see p. 110), α-ketoglutarate dehydrogenase of the tricarboxylic acid cycle (see p. 112), and branched-chain α-keto acid dehydrogenase of branched-chain amino acid catabolism (see p. 266).
IV. NADPH USES
The coenzyme NADPH differs from nicotinamide adenine dinucleotide (NADH) only by the presence of a phosphate group on one of the ribose units (Fig. 13.4). This seemingly small change in structure allows NADPH to interact with NADPH-specific enzymes that have unique roles in the cell. For example, in the cytosol of hepatocytes, the steady-state NADP+/NADPH ratio is ~0.1, which favors the use of NADPH in reductive biosynthetic reactions. This contrasts with the high NAD+/NADH ratio (~1,000), which favors an oxidative role for NAD+. This section summarizes some important NADPH-specific functions in reductive biosynthesis and detoxification reactions.
A. Reductive biosynthesis