6.1: Introduction

We used to get free metabolic pathway wall charts like this one from vendors of biochemical reagents. The big picture is correct (as noted, a sizable version is available at the link below the chart), but the charts may be out of date in small details of metabolism. In this chapter, we’ll zoom in on the middle of the chart, encompassing glycolysis and the Krebs cycle (named for Hand Krebs, its discoverer) to see how thermodynamic laws apply to chemical reactions. We’ve looked at the principles governing thermodynamics (the flow of energy in the universe) and bioenergetics (energy flow in living systems). We saw evidence that energy is exchanged between components in the universe, but that it can be neither created nor destroyed. That makes the universe a closed system, a conclusion codified as the first law of thermodynamics. Personally, I find the idea of a closed universe troubling since there is no escape from it—that is, until I remind myself that the universe is a big place, and I am only a small part of a small system that you can define for yourself: the solar system, planet Earth, the country you pledge allegiance to, your city or village, your school, your farm, or your homestead!

You may derive comfort from the realization that you can move from one system to another and even exchange goods and services between them. This is a metaphor for energy flow between systems in the universe. We also saw that the first law applies to closed systems within the universe, and that there are no closed systems in the universe! Any system in the universe is open, always exchanging energy and mass with neighboring systems. What we mean by the term closed system is that we can define and isolate some small part of the universe and then measure any energy that this isolated system gives up to its environment or takes in from it. The simplest demonstration of the first law in action is the bomb calorimeter, which measures heat released or absorbed during a chemical reaction.

A second thermodynamic concept says that energy flows from one place to another only when it can. In the vernacular, we say that energy flows downhill. Anything that happens in the universe (a galaxy moving through space, a planet rotating, you getting out of bed in the morning, coffee perking you up, your cells burning sugar, DNA replicating…) does so because energy flows downhill. We saw that any happening or event in the universe, however large or small, must be spontaneous. That is, it occurs with a release of free energy. Remember, spontaneous means “by itself” and not necessarily “instantaneous” or “fast”! Finally, we noted that when enzymes catalyze biochemical reactions in a closed system, the reactions still reach equilibrium, despite the higher rate of the catalyzed reaction. What does this tell you about the energetics of catalyzed reactions in closed systems?

With this brief reminder about energy flow and what enzymes do, we’ll look at how our cells capture nutrient free energy (the chemical energy in foods), a topic that will include examples of the energetics of closed systems that reach equilibrium and open systems that don’t! First, we tackle glycolysis, an anaerobic fermentation pathway for generating chemical energy from glucose, as well as the first of several aerobic pathways of respiration. We’ll see that most of the energy from glycolysis and respiration is captured in molecules of ATP, the universal energy currency of life, used by cells to…live! Then we look at gluconeogenesis, a regulated reversal of glycolysis. We ask when, where, and why we would want to make rather than burn glucose. Finally, we begin a discussion of respiration with a look at the Krebs cycle. The complete respiratory pathway can be summarized by the following equation:

\(C_6H_{12}O_6 + 6O_2 \rightleftharpoon 6CO_2 + 6H_2O\)

The standard free energy change for this reaction (\(\Delta Go\)) is about −687 Kcal/mol. This is the maximum amount of nutrient free energy that is (at least in theory) available from the complete respiration of a mole of glucose. Given a cost of about 7.3 Kcal to make each mole of ATP (adenosine triphosphate), how many moles of ATP might a cell produce after burning a mole of glucose? We’ll figure this out here.

learning Objectives

When you have mastered the information in this chapter, you should be able to:

1. explain the difference between fermentation and respiratory glycolysis and the role of redox reactions in both processes.

2. calculate and then compare and contrast DGo and DG’ for the same reaction, and explain any differences in free energy in open and closed systems.

3. describe and explain the major events of the first stage of glycolysis and trace the free energy changes through the formation of G-3-P.

4. describe and explain the major events of the second stage of glycolysis and trace the free energy changes through the formation of pyruvate and lactic acid.

5. state the role of redox reactions in glycolysis and fermentation.

6. compare and contrast glucose (i.e., carbohydrates in general), ATP, NADH and FADH2 as high-energy molecules. [Just for fun, click Power in the Primordial Soup to read some far out speculations on prebiotic high-energy molecules that might have been around when ATP was being hired for the job!].

7. explain why only a few cell types in the human body conduct gluconeogenesis.

8. explain why gluconeogenesis, an energetically unfavorable pathway, occurs at all.

9. explain why the Atkins Diet works and speculate on its downside (and that of the related South Beach Diet).

10. explain the concept of a super-catalyst.

11. explain why a super-catalyst like the Krebs Cycle would have evolved.

12. explain the role of high energy linkages and electron carriers in the Krebs cycle.

13. compare phosphate ester linkages in ATP and GTP, and thioester linkage in acetyl-S- CoA and succinyl-S-CoA in terms of energetics and their biochemical reactions.

speculate on why the Krebs Cycle in E. coli generates GTP molecules and why it generates ATP molecules eukaryotes.