Question

The concept of energy charge is a very useful way to think about how ATP levels control pathway activity. Discuss the role of ATP in the glycolytic pathway (between glucose and pyruvate and/or lactate) with a focus on how energy charge would alter the pathway and how the pathway activity would alter energy charge. Include both general aspects and specific ATP use and generation.

Answer 1

Cytosolic Enzymes Convert Glucose to Pyruvate

A set of 10 enzymes catalyze the reactions, constituting the glycolytic pathway, that degrade one molecule of glucose to two molecules of pyruvate (Figure 16-3). All the metabolic intermediates between glucose and pyruvate are watersoluble phosphorylated compounds. Four molecules of ATP are formed from ADP in glycolysis (reactions 6 and 9). However, two ATP molecules are consumed during earlier steps of this pathway: the first by the addition of a phosphate residue to glucose in the reaction catalyzed by hexokinase (reaction 1), and the second by the addition of a second phosphate to fructose 6-phosphate in the reaction catalyzed by phosphofructokinase-1 (reaction 3). Thus there is a net gain of two ATP molecules.

Figure 16-3

The glycolytic pathway by which glucose is degraded to pyruvic acid. Reactions in which ATP and ADP are involved are highlighted in blue; the reaction involving NAD and NADH is highlighted (more...)

The balanced chemical equation for the conversion of glucose to pyruvate shows that four hydrogen atoms (four protons and four electrons) are also formed:

(For convenience, we show pyruvate in its un-ionized form, pyruvic acid, although at physiological pH it would be largely dissociated.) All four electrons and two of the four protons are transferred to two molecules of the oxidized form of the electron carrier nicotinamide adenine dinucleotide (NAD+) to produce the reduced form, NADH (Figure 16-4):

The reaction that generates these hydrogen atoms and transfers them to NAD+ is catalyzed by glyceraldehyde 3-phosphate dehydrogenase (see Figure 16-3, reaction 5).

Figure 16-4

Structures of the electron-carrying coenzymes NAD+ and NADH. Nicotinamide adenine dinucleotide (NAD+) and the related nicotinamide adenine dinucleotide phosphate (more...)

Thus the overall reaction for this first stage of glucose metabolism is