Question

how can you make 2 moles of fructose 6 phosphate using 3 moles of glucose 6 phosphate in the pentose phosphate pathway?

Answer 1

The first reaction in the oxidative branch of the pentose phosphate pathway, the dehydrogenation of glucose 6-phosphate, 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.

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 6-phosphate in the oxidative phase of the pentose phosphate pathway. The stoichiometry of mode 2 is

Glucose 6-phosphate + 2 NADP H20 ribose 5-phosphate + 2 NADPH 2H CO2

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

6 Glucose 6-phosphate 12 NADP+ 6H2O-> 6 ribose 5-phosphate 12 NADPH 12 H+ 6 CO2

6 Ribose 5-phosphate-> 4 fructose 6-phosphate 2 glyceraldehyde 3-phosphate

4 Fructose 6-phosphate + 2 glyceraldehyde 3-phosphate + H2O→ 5 glucose 6-phosphate P