An Overview: Releasing Energy from Glucose

Depending on the presence or absence of O₂, the energy-harvesting processes in cells use different combinations of metabolic pathways:

When O₂ is available as the final electron acceptor, four pathways operate. Glycolysis takes place first and is followed by three pathways of cellular respiration: pyruvate oxidation, the citric acid cycle and the respiratory chain (also known as the electron transport chain).

When O₂ is unavailable, pyruvate oxidation, the citric acid cycle, and the respiratory chain do not function, and the pyruvate produced by glycolysis is further metabolized by fermentation. These five metabolic pathways, which we will consider at a time, have different locations in the cell.

Glycolysis: From Glucose to Pyruvate

We begin our discussion of the energy-harvesting pathways with glycolysis which begins glucose metabolism. Glycolysis takes place in the cytoplasm of cells. It converts glucose to pyruvate, produces a small amount of energy and does not generate CO₂. In glycolysis, a reduced fuel molecule, glucose, gets partially oxidized and in the process releases some of its energy. After ten enzyme-catalyzed reactions, the end products of glycolysis are two molecules of pyruvate (pyruvic acid)*. These reactions are accompanied by the net formation of two molecules of ATP and by the reduction of two molecules of NAD+ to two molecules of NADH + H+ for each molecule of glucose. Glycolysis can be divided into two stages: energy-investing reactions that use ATP, and energy-harvesting reactions that produce ATP.

The energy-investing reactions of glycolysis require ATP

The first five reactions of glycolysis are endergonic; that is, the cell is investing free energy in the glucose molecule, rather than releasing energy from it. In two separate reactions, the energy of two molecules of ATP is invested in attaching two phosphate groups to the glucose molecule to form fructose 1,6-bisphosphate,* which has a free energy substantially higher than that of glucose. Later, these phosphate groups will be transferred to ADP to make new molecules of ATP. Although both of these first steps of glycolysis use ATP as one of their substrates, each is catalyzed by a different, specific enzyme. The enzyme hexokinase catalyzes reaction 1, in which a phosphate group from ATP is attached to the sixcarbon glucose molecule, forming glucose 6-phosphate. (A kinase is any enzyme that catalyzes the transfer of a phosphate group from ATP to another substrate.) In reaction 2, the six-membered glucose ring is rearranged into a fivemembered fructose ring. In reaction 3, the enzyme phosphofructokinase adds a second phosphate (taken from another ATP) to the fructose ring, forming a six-carbon sugar, fructose 1,6-bisphosphate. Reaction 4 opens up and cleaves the six-carbon sugar ring to give two different three-carbon sugar phosphates: dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. In reaction 5, one of those products, dihydroxyacetone phosphate, is converted into a second molecule of the other one, glyceraldehyde 3-phosphate (G3P). By this time—the halfway point of the glycolytic pathway— the following things have happened:

Two molecules of ATP have been invested.

The six-carbon glucose molecule has been converted into two molecules of a three-carbon sugar phosphate, glyceraldehydes 3-phosphate (G3P, a triose phosphate).

The energy-harvesting reactions of glycolysis yield NADH + H+ and ATP

With the investment of two ATPs, the first five reactions of glycolysis have rearranged the six-carbon sugar glucose and split it into two three-carbon sugar phosphates (G3P). In the discussion that follows, remember that each reaction occurs twice for each glucose molecule going through glycolysis because each glucose molecule has been split into two molecules of G3P. It is the fate of G3P that now concerns us—its transformation will generate both NADH + H+ and ATP.

Producing NADH + H+.

Reaction 6 is catalyzed by the enzyme triose phosphate dehydrogenase, and its end product is a phosphate ester, 1,3-bisphosphoglycerate (BPG). Reaction 6 is an oxidation and it is accompanied by an enormous drop in free energy — more than 100 kcal of energy per mole of glucose is released in this extremely exergonic reaction. If this big energy drop were simply a loss of heat, glycolysis would not provide useful energy to the cell. However, rather than being lost as heat, this energy is stored as chemical energy by reducing two molecules of NAD+ to make two molecules of NADH + H+. Because NAD+ is present in small amounts in the cell, it must be recycled to allow glycolysis to continue; if none of the NADH is oxidized back to NAD+, glycolysis comes to a halt. The metabolic pathways that follow glycolysis carry out this oxidation, as we will see.

Producing ATP.

In reactions 7–10, the two phosphate groups of BPG are transferred one at a time to molecules of ADP, with a rearrangement in between. More than 20 kcal (83.6 kJ/mol) of free energy is stored in ATP for every mole of BPG broken down. Finally, we are left with two moles of pyruvate for every mole of glucose that entered glycolysis.

The enzyme-catalyzed transfer of phosphate groups from donor molecules to ADP molecules (as in reaction 7) is called substrate-level phosphorylation. (Phosphorylation is the addition of a phosphate group to a molecule. Substrate-level phosphorylation is distinguished from the oxidative phosphorylation carried out by the respiratory chain, which we will discuss later in the chapter.) As an example of substrate-level phosphorylation, when G3P reacts with a phosphate group (Pi) and NAD+ in reaction 6, a second phosphate is added, an aldehyde is oxidized to a carboxylic acid, NAD+ is reduced and BPG is formed. The oxidation provides so much energy that the newly added phosphate group is linked to the rest of the molecule by a covalent bond that has even more energy than the terminal phosphate-to-phosphate bond of ATP. Another example of substrate-level phosphorylation occurs in reaction 7, where phosphoglycerate kinase catalyzes the transfer of a phosphate group from BPG to ADP forming ATP. Both reactions 6 and 7 are exergonic, even though a substantial amount of energy is consumed in the formation of ATP. A review of the glycolytic pathway shows that at the beginning of glycolysis, two molecules of ATP are used per molecule of glucose, but that ultimately four molecules of ATP are produced (two for each of the two BPG molecules)— a net gain of two ATP molecules and two NADH + H+.

Glycolysis is followed by cellular respiration (if O₂ is present) or fermentation (if no O₂ is present). The first reaction of cellular respiration is the oxidation of pyruvate.

Date: 2014-12-22; view: 917