Metabolic pathways are regulated systems

The regulation of interconnecting biochemical pathways is a problem of systems biology, which seeks to understand how biochemical pathways interact (see Key Concept 8.5). It is a bit like trying to predict traffic patterns in a city: if an accident blocks traffic on a major road, drivers take alternate routes, where the traffic volume consequently changes.

Several mechanisms can be used to regulate the rate of each step in a biochemical pathway:

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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. But before the glucose is distributed, a regulatory check must be made: If there is already enough glucose in the blood to supply the body’s needs, the excess glucose is converted into glycogen and stored in the liver and muscles. If not enough glucose is supplied by food, 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. How does the body accomplish this?

Glycolysis and the citric acid cycle are subject to allosteric regulation (see Key Concept 8.5) of key enzymes involved. In a metabolic pathway, a high concentration of the final product can inhibit the action of an enzyme that catalyzes an earlier reaction (see Figure 8.18). Furthermore, an excess of the product of one pathway can activate an enzyme in another pathway, speeding up its reactions and diverting raw materials away from synthesis of the first product (Figure 9.15). These negative and positive feedback mechanisms are used at many points in the energy-harvesting pathways and are summarized in Figure 9.16.

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Figure 9.15 Regulation by Negative and Positive Feedback Allosteric feedback regulation plays an important role in metabolic pathways. The accumulation of some products can shut down their synthesis, or can stimulate other pathways that require the same raw materials.

Activity 9.7 Regulation of Energy Pathways

www.life11e.com/ac9.7

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Figure 9.16 Allosteric Regulation of Glycolysis and the Citric Acid Cycle Allosteric regulation controls glycolysis and the citric acid cycle at crucial early steps, increasing their efficiency and preventing the excessive buildup of intermediates.