The Metabolism of Glucose 6Phosphate by the Pentose Phosphate Pathway Is Coordinated with Glycolysis

II. Transducing and Storing Energy
20. The Calvin Cycle and the Pentose Phosphate Pathway
20.4. The Metabolism of Glucose 6-Phosphate by the Pentose Phosphate Pathway Is
Coordinated with Glycolysis
Conceptual Insights, Overview of Carbohydrate and Fatty Acid Metabolism.
View this media module to gain a "bigger picture" understanding of the roles of
the pentose phosphate pathway in the context of other metabolic pathways
(glycolysis, citric acid cycle, glycogen and fatty acid metabolism).
Glucose 6-phosphate is metabolized by both the glycolytic pathway (Chapter 16) and the pentose phosphate pathway.
How is the processing of this important metabolite partitioned between these two metabolic routes? The cytoplasmic
concentration of NADP+ plays a key role in determining the fate of glucose 6-phosphate.
20.4.1. The Rate of the Pentose Phosphate Pathway Is Controlled by the Level of NADP
+
The first reaction in the oxidative branch of the pentose phosphate pathway, the dehydrogenation of glucose 6phosphate, is essentially irreversible. In fact, this reaction is rate limiting under physiological conditions and serves as
the control site. The most important regulatory factor is the level of NADP+, the electron acceptor in the oxidation of
glucose 6-phosphate to 6-phosphoglucono-δ-lactone. The inhibitory effect of low levels of NADP+ is exacerbated by the
fact that NADPH competes with NADP+ in binding to the enzyme. The ratio of NADP+ to NADPH in the cytosol of a
liver cell from a well-fed rat is about 0.014, several orders of magnitude lower than the ratio of NAD+ to NADH, which
is 700 under the same conditions. The marked effect of the NADP+ level on the rate of the oxidative phase ensures that
NADPH generation is tightly coupled to its utilization in reductive biosyntheses. The nonoxidative phase of the pentose
phosphate pathway is controlled primarily by the availability of substrates.
20.4.2. The Flow of Glucose 6-phosphate Depends on the Need for NADPH, Ribose 5phosphate, and ATP
We can grasp the intricate interplay between glycolysis and the pentose phosphate pathway by examining the
metabolism of glucose 6-phosphate in four different metabolic situations (Figure 20.24).
Mode 1. Much more ribose 5-phosphate than NADPH is required. For example, rapidly dividing cells need ribose 5phosphate for the synthesis of nucleotide precursors of DNA. Most of the glucose 6-phosphate is converted into fructose
6-phosphate and glyceraldehyde 3-phosphate by the glycolytic pathway. Transaldolase and transketolase then convert
two molecules of fructose 6-phosphate and one molecule of glyceraldehyde 3-phosphate into three molecules of ribose 5phosphate by a reversal of the reactions described earlier. The stoichiometry of mode 1 is
Mode 2. The needs for NADPH and ribose 5-phosphate are balanced. The predominant reaction under these conditions
is the formation of two molecules of NADPH and one molecule of ribose 5-phosphate from one molecule of glucose 6phosphate in the oxidative phase of the pentose phosphate pathway. The stoichiometry of mode 2 is
Mode 3. Much more NADPH than ribose 5-phosphate is required. For example, adipose tissue requires a high level of
NADPH for the synthesis of fatty acids (Table 20.4). In this case, glucose 6-phosphate is completely oxidized to CO2.
Three groups of reactions are active in this situation. First, the oxidative phase of the pentose phosphate pathway forms
two molecules of NADPH and one molecule of ribose 5-phosphate. Then, ribose 5-phosphate is converted into fructose
6-phosphate and glyceraldehyde 3-phosphate by transketolase and transaldolase. Finally, glucose 6-phosphate is
resynthesized from fructose 6-phosphate and glyceraldehyde 3-phosphate by the gluconeogenic pathway. The
stoichiometries of these three sets of reactions are
The sum of the mode 3 reactions is
Thus, the equivalent of glucose 6-phosphate can be completely oxidized to CO2 with the concomitant generation of
NADPH. In essence, ribose 5-phosphate produced by the pentose phosphate pathway is recycled into glucose 6phosphate by transketolase, transaldolase, and some of the enzymes of the gluconeogenic pathway.
Mode 4. Both NADPH and ATP are required. Alternatively, ribose 5-phosphate formed by the oxidative phase of the
pentose phosphate pathway can be converted into pyruvate. Fructose 6-phosphate and glyceraldehyde 3-phosphate
derived from ribose 5-phosphate enter the glycolytic pathway rather than reverting to glucose 6-phosphate. In this mode,
ATP and NADPH are concomitantly generated, and five of the six carbons of glucose 6-phosphate emerge in pyruvate.
Pyruvate formed by these reactions can be oxidized to generate more ATP or it can be used as a building block in a
variety of biosyntheses.
20.4.3. Through the Looking Glass: The Calvin Cycle and the Pentose Phosphate
Pathway
The complexities of the Calvin cycle and the pentose phosphate pathway are easier to comprehend if we consider them
mirror images of each other. The Calvin cycle begins with the fixation of CO2 and goes on to use NADPH in the
synthesis of glucose. The pentose phosphate pathway begins with the oxidation of a glucose-derived carbon atom to CO2
and concomitantly generates NADPH. The regeneration phase of the Calvin cycle converts C6 and C3 molecules back
into the starting material the C5 molecule ribulose 1,5-bisphosphate. The pentose phosphate pathway converts a C5
molecule, ribose 5-phosphate, into C6 and C3 intermediates of the glycolytic pathway. Not surprisingly, in
photosynthetic organisms, many enzymes are common to the two pathways. We see the economy of evolution: the use of
identical enzymes for similar reactions with different ends.
II. Transducing and Storing Energy
20. The Calvin Cycle and the Pentose Phosphate Pathway
20.4. The Metabolism of Glucose 6-Phosphate by the Pentose Phosphate Pathway Is Coordinated with Glycolysis
Figure 20.24. Four Modes of the Pentose Phosphate Pathway. Major products are shown in color.
II. Transducing and Storing Energy
20. The Calvin Cycle and the Pentose Phosphate Pathway
20.4. The Metabolism of Glucose 6-Phosphate by the Pentose Phosphate Pathway Is Coordinated with Glycolysis
Table 20.4. Tissues with active pentose phosphate pathways
Tissue
Function
Adrenal gland
Liver
Testes
Adipose tissue
Ovary
Steroid synthesis
Fatty acid and cholesterol synthesis
Steroid synthesis
Fatty acid synthesis
Steroid synthesis