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Glucose is a carbohydrate that’s made up of six carbon, six oxygen, and twelve hydrogen atoms. Glucose molecules may be drawn in different ways. The linear form of the glucose molecule is in equilibrium with its cyclic, or ring, forms. The ring with six atoms is the most stable form. Glucose supplies energy to our brain, muscles, blood cells, and other body parts. When we eat sugars and other carbohydrates, they are broken down to glucose, which can then enter the glycolytic pathway.
Energy is released when carbon is oxidized. You saw that heat and light are released when the carbon in wood is burned. Oxidation reactions are always coupled to reduction reactions. When one molecule loses electrons, another molecule gains them. In catabolic pathways such as glycolysis, oxidation reactions are often coupled to the reduction of the coenzyme NAD.
In glycolysis, glucose is converted to pyruvate through a series of ten enzyme-catalyzed reactions. Although occurring in both aerobic and anaerobic pathways, glycolysis itself is an anaerobic process, and it doesn’t generate a lot of energy. As we’ll see, the big energy payoff in terms of ATP production comes during aerobic metabolism.
Glycolysis takes place in the cytoplasm of eukaryotic and prokaryotic cells,
and anaerobic fermentation pathways are completed in the cytoplasm. In eukaryotes, the aerobic metabolism of glucose is completed in the mitochondria, which have evolved specialized protein complexes for this task.
Glycolysis occurs in two phases. An old adage may help you understand why. In business and finance, it is said “It takes money to make money.” This is also true in biology if the concept of money is replaced with the concept of energy.
Sometimes bonds have to be made and rearranged to efficiently harvest the energy stored in a molecule. Such reactions may be endergonic and require the input of energy, often in the form of ATP. This is what happens in glycolysis.
In the first phase of glycolysis, two molecules of ATP are invested per glucose molecule. The return on this investment comes in the second phase where ATP is made by the direct transfer of a phosphate to ADP. The payoff in the second phase is four molecules of ATP per glucose molecule. The net return for the conversion of one glucose molecule into two pyruvate molecules is four minus two, or two molecules of ATP.
In the first reaction, a phosphate group is transferred from ATP to glucose. This reaction takes place with the help of the enzyme hexokinase. This reaction consumes glucose, lowering its intracellular concentration and making it easier for more glucose to enter the cell. The coupling of glucose phosphorylation to ATP hydrolysis makes it thermodynamically favored. The large negative free energy change guarantees that the reaction proceeds spontaneously in the forward direction.
The second reaction of glycolysis involves a rearrangement of chemical bonds. Although enzymes can do many wonderful things, bonds often need to be rearranged to make other reactions possible. This type of bond rearrangement is called isomerization, and the enzyme that assists in the reaction is called an isomerase. This step gets the molecule ready for the next enzyme-catalyzed reaction.
The third reaction of glycolysis is similar to the first in that a molecule of ATP is consumed. A second phosphate is added to the substrate. This reaction is catalyzed by the enzyme phosphofructokinase or PFK. As in reaction 1, the addition of a phosphate is coupled to ATP hydrolysis. The overall reaction has a large negative free energy change, making the reaction spontaneous.
In reaction 4, the sugar is split into two different molecules, each with 3 carbon atoms. The enzyme aldolase catalyzes the reaction. Since the two molecules produced in reaction 4 are different, reaction 5 rearranges one of them so that two identical molecules of glyceraldehyde-3-phosphate enter phase 2 of glycolysis, the payoff phase. Reaction 5 is catalyzed by another isomerase.
We’re now going to enter the second phase of glycolysis, where ATP is generated.
Reaction 6 is the first enzyme-catalyzed oxidation-reduction reaction in glycolysis. It’s easy to recognize because the coenzyme NAD is involved. As the substrate from reaction 5, glyceraldehyde-3-phosphate, is oxidized, it loses a hydride ion, H-minus, and gains oxygen. Whenever a molecule is oxidized, another must be reduced. NAD is reduced when it accepts the hydride ion. Some of the energy released by oxidation is stored in NADH, the reduced form of NAD. And some of the oxidation energy is used to add another phosphate to the substrate. In the previous phosphorylation reactions, 1 and 3, the energy stored in ATP was used to drive the reactions.
In reaction 7, a phosphate group is transferred to ADP to produce ATP. This is the break-even step of the glycolytic pathway. Two ATP molecules were consumed in phase 1 and two ATP molecules are made in this reaction, as the two substrate molecules formed in phase 1 pass through.
Reactions 8 and 9 are isomerization reactions that prepare the substrate for another ATP-generating step. In reaction 8, the phosphate is moved to the middle carbon. In reaction 9, a water molecule is removed.
Reaction 10 completes glycolysis. With the assistance of the enzyme pyruvate kinase, this reaction produces two more molecules of ATP and two molecules of pyruvate. Like reactions 1 and 3, reaction 10 has a large, negative free energy change.
Let’s look at the profits and losses of our energy transactions. Two ATP molecules are consumed in phase 1 and four ATP molecules are made in phase 2. The net amount of ATP generated in glycolysis is two molecules of ATP. In addition to ATP, glycolysis yields two NADH molecules and two pyruvate molecules per glucose molecule.
In the next section, we’ll see what happens to these other molecules.
Copyright 2006 The Regents of the University of California and Monterey Institute for Technology and Education