During fasting: By contrast, the elevated levels of glucagon and low levels of insulin that occur during fasting (see p. 327) cause a decrease in hepatic fructose 2,6-bisphosphate (PFK-2 is phosphorylated). This results in inhibition of glycolysis and activation of gluconeogenesis.
D. Fructose 1,6-bisphosphate cleavage
Aldolase cleaves fructose 1,6-bisphosphate to dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (see Fig. 8.16). The reaction is reversible and not regulated. [Note: Aldolase B, the hepatic isoform, also cleaves fructose 1-phosphate and functions in dietary fructose metabolism (see p. 138).]
E. Dihydroxyacetone phosphate isomerization
Triose phosphate isomerase interconverts DHAP and glyceraldehyde 3phosphate (see Fig. 8.16). DHAP must be isomerized to glyceraldehyde 3phosphate for further metabolism by the glycolytic pathway. This isomerization results in the net production of two molecules of glyceraldehyde 3-phosphate from the cleavage products of fructose 1,6bisphosphate. [Note: DHAP is utilized in triacylglycerol synthesis (see p. 188).]
F. Glyceraldehyde 3-phosphate oxidation
The conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate (1,3-BPG) by glyceraldehyde 3-phosphate dehydrogenase is the first oxidation-reduction reaction of glycolysis (Fig. 8.18). [Note: Because there is a limited amount of NAD+ in the cell, the NADH formed by the dehydrogenase reaction must be oxidized for glycolysis to continue. Two major mechanisms for oxidizing NADH to NAD+ are the reduction of pyruvate to lactate by lactate dehydrogenase (LDH) (anaerobic, see p. 96) and the electron transport chain ([ETC] aerobic, see p. 74). Because NADH cannot cross the inner mitochondrial membrane, the ETC requires the malate-aspartate and glycerol 3-phosphate substrate shuttles to move NADH reducing equivalents into the mitochondrial matrix (see p. 79).] 1.
1,3-Bisphosphoglycerate synthesis: The oxidation of the aldehyde group of glyceraldehyde 3-phosphate to a carboxyl group is coupled to the attachment of Pi to the carboxyl group. This phosphate group, linked to carbon 1 of the 1,3-BPG product by a high-energy bond (see p. 73), conserves much of the free energy (see p. 69) produced by the oxidation of glyceraldehyde 3-phosphate. This high-energy phosphate drives ATP synthesis in the next reaction of glycolysis.
2.