Regulating Energy Pathways

We have described the relationships between metabolic pathways and noted that these pathways work together to provide homeostasis in the cell and organism. But how does the cell regulate interconversions between these pathways to maintain constant metabolic pools?

Consider what happens to the starch in your burger bun. In the digestive system, starch is hydrolyzed to glucose, which enters the blood for distribution to the rest of the body. Before this happens, however, a "decision" must be made: Is there already enough glucose in the blood to supply the body's needs? If there is, the excess glucose is converted to stored glycogen in the liver. If not enough glucose is supplied by food, liver glycogen is broken down, or other molecules are used to make glucose by gluconeogenesis.

The end result is that the level of glucose in the blood is remarkably constant. We will describe the details of how this happens in Part Seven of this book. For now, it is important to realize that the interconversions of glucose involve many steps, each catalyzed by an enzyme, and it is here that controls often reside.

Glycolysis, the citric acid cycle, and the respiratory chain are regulated by allosteric control of the enzymes involved. In metabolic pathways, as we saw in Chapter 6, a high concentration of the products of a later reaction can suppress the action of enzymes that catalyze an earlier reaction. On the other hand, an excess of the product of one branch of a synthetic chain can speed up reactions in another branch, diverting raw materials away from synthesis of the first product (Figure 7.19). These negative and positive feedback control mechanisms are used at many points in the energy-harvesting pathways, which are summarized in Figure 7.20.

The main control point in glycolysis is the enzyme phos-phofructokinase (reaction 3 in Figure 7.6). This enzyme is al-losterically inhibited by ATP and activated by ADP or AMP.

As long as fermentation proceeds, yielding a relatively small amount of ATP, phosphofructokinase operates at full efficiency. But when cellular respiration begins producing 18 times more ATP than fermentation does, the abundant ATP allosterically inhibits the enzyme, and the conversion of fructose 6-phosphate to fructose 1,6-bisphosphate declines, as does the rate of glucose utilization.

The main control point in the citric acid cycle is the enzyme isocitrate dehydrogenase, which converts isocitrate to a-ke-toglutarate (reaction 3 in Figure 7.8). NADH + H+ and ATP are feedback inhibitors of this reaction; ADP and NAD+ are activators (Figure 7.20). If too much ATP is accumulating, or if NADH + H+ is being produced faster than it can be used by the respiratory chain, the conversion of isocitrate is slowed, and the citric acid cycle is essentially shut down. A shutdown of the citric acid cycle would cause large amounts of isocitrate and citrate to accumulate if the conversion of acetyl CoA to citrate were not also slowed by abundant ATP and NADH + H+. However, a certain excess of citrate does accumulate, and this excess acts as an additional negative feedback inhibitor to slow the fructose 6-phosphate reaction early in glycolysis. Consequently, if the citric acid cycle has been slowed down because of abundant ATP (and not because of a lack of oxygen), gly-colysis is shut down as well. Both processes resume when the ATP level falls and they are needed again. Allosteric control keeps these processes in balance.

Another control point involves a method for storing excess acetyl CoA. If too much ATP is being made and the citric acid cycle shuts down, the accumulation of citrate switches acetyl CoA to the synthesis of fatty acids for storage. This is one reason why people who eat too much accumulate fat. These fatty acids may be metabolized later to produce more acetyl CoA.

Negative Feedback Control Glycolysis

7.20 Feedback Regulation of Glycolysis and the Citric Acid Cycle Feedback controls glycolysis and the citric acid cycle at crucial early steps, increasing their efficiency and preventing the excessive buildup of intermediates.

► Glycolysis operates in the presence or absence of O2. Under aerobic conditions, cellular respiration continues the process of breaking down glucose. Under anaerobic conditions, fermentation occurs. Review Figure 7.5. See Web/CD Activity 7.1

► Cellular respiration consists of three pathways: pyruvate oxidation, the citric acid cycle, and the respiratory chain.

► Pyruvate oxidation and the citric acid cycle produce CO2 and hydrogen atoms carried by NADH and FADH2. The respiratory chain combines these hydrogens with O2, releasing enough energy for the synthesis of ATP. Review Figure 7.5

► In eukaryotes, glycolysis and fermentation take place in the cytoplasm outside of the mitochondria; pyruvate oxidation, the citric acid cycle, and the respiratory chain operate in association with mitochondria. In prokaryotes, glycolysis, fermentation, and the citric acid cycle take place in the cytoplasm, and pyru-vate oxidation and the respiratory chain operate in association with the plasma membrane. Review Table 7.1. See Web/CD Activity 7.2

Glycolysis: From Glucose to Pyruvate

► Glycolysis is a pathway of ten enzyme-catalyzed reactions located in the cytoplasm. Glycolysis provides starting materials for both cellular respiration and fermentation. Review Figure 7.6

► The energy-investing reactions of glycolysis use two ATPs per glucose molecule and eventually yield two G3P molecules. In the energy-harvesting reactions, two NADH molecules are produced, and four ATP molecules are generated by substrate-level phosphory-lation. Two pyruvate molecules are produced for each glucose molecule. Review Figures 7.6, 7.7

7.20 Feedback Regulation of Glycolysis and the Citric Acid Cycle Feedback controls glycolysis and the citric acid cycle at crucial early steps, increasing their efficiency and preventing the excessive buildup of intermediates.

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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Responses

  • kian
    Why energy pathways involve many small regulated steps?
    8 years ago
  • yohannes
    How is glycolysis regulated?
    7 years ago

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