Metabolic States - Bioenergetics and Regulation of Metabolism - MCAT Biochemistry Review

MCAT Biochemistry Review

Chapter 12: Bioenergetics and Regulation of Metabolism

12.4 Metabolic States

One of the key differences between chemistry and biochemistry is whether or not equilibrium is seen as a desirable state. Biochemists emphatically believe that it is not! Equilibrium is a fixed state, which prevents us from storing any energy for later use or creating an excitable environment. Instead, biochemists seek a state of homeostasis. Homeostasis is a physiological tendency toward a relatively stable state that is maintained and adjusted, often with the expenditure of energy. Most compounds in the body are actually maintained at a homeostatic level that is different from equilibrium, which allows us to store potential energy; for example, keeping sodium concentrations much higher outside a neuron than inside it creates a gradient that stores energy. In this state, reactions can proceed such that equilibrium is put off for a long time (someone born today can delay equilibrium for about 80 years).

The pathways that are operational in fuel metabolism depend on the nutritional status of the organism. Shifts between storage and mobilization of a particular fuel, as well as shifts among the types of fuel being used, are very pronounced when going from the well-fed state to an overnight fast, and finally to a prolonged state of starvation. We'll take a look at how fuel metabolism is regulated in each state. Remember that in addition to the “big-picture view” discussed here, the specific regulatory steps of each pathway are discussed in the previous chapters of MCAT Biochemistry Review: Chapter 9 (glycolysis, glycogenesis, glycogenolysis, gluconeogenesis, and the pentose phosphate pathway), Chapter 10 (the citric acid cycle, electron transport chain, and oxidative phosphorylation), and Chapter 11 (lipid synthesis, β-oxidation, ketogenesis and ketolysis, and amino acid metabolism).


The postprandial state, also called the absorptive or well-fed state, occurs shortly after eating. This state is marked by greater anabolism (synthesis of biomolecules) and fuel storage than catabolism (breakdown of biomolecules for energy). Nutrients flood in from the gut and make their way via the hepatic portal vein to the liver, where they can be stored or distributed to other tissues of the body. The postprandial state generally lasts three to five hours after eating a meal.

Just after eating, blood glucose levels rise and stimulate the release of insulin. The three major target tissues for insulin are the liver, muscle, and adipose tissue, as shown in Figure 12.2. Insulin promotes glycogen synthesis in liver and muscle. After the glycogen stores are filled, the liver converts excess glucose to fatty acids and triacylglycerols. Insulin promotes triacylglycerol synthesis in adipose tissue and protein synthesis in muscle, as well as glucose entry into both tissues. After a meal, most of the energy needs of the liver are met by the oxidation of excess amino acids.

Two types of cells—nervous tissue and red blood cells—are insensitive to insulin. Nervous tissue derives energy from oxidizing glucose to CO2 and water in both the well-fed and normal fasting states. Only in prolonged fasting does this situation change. Red blood cells can only use glucose anaerobically for all their energy needs, regardless of the individual's metabolic state.

Figure 12.2. Metabolic Profile of the Postprandial (Absorptive) State


Glucagon, cortisol, epinephrine, norepinephrine, and growth hormone oppose the actions of insulin. These hormones are sometimes termed counterregulatory hormones because of their effects on skeletal muscle, adipose tissue, and the liver, which are opposite to the actions of insulin. In the liver, glycogen degradation and the release of glucose into the blood are stimulated, as shown in Figure 12.3. Hepatic gluconeogenesis is also stimulated by glucagon, but the response is slower than that of glycogenolysis. Whereas glycogenolysis begins almost immediately at the beginning of the postabsorptive state, gluconeogenesis takes about 12 hours to hit maximum velocity.

The release of amino acids from skeletal muscle and fatty acids from adipose tissue are both stimulated by the decrease in insulin and by an increase in levels of epinephrine. Once carried into the liver, amino acids and fatty acids can provide the necessary carbon skeletons and energy required for gluconeogenesis.

Figure 12.3. Metabolic Profile of the Postabsorptive (Fasting) State


Levels of glucagon and epinephrine are markedly elevated during starvation. Increased levels of glucagon relative to insulin result in rapid degradation of glycogen stores in the liver. As liver glycogen stores are depleted, gluconeogenesis activity continues and plays an important role in maintaining blood glucose levels during prolonged fasting; after about 24 hours, gluconeogenesis is the predominant source of glucose for the body. Lipolysis is rapid, resulting in excess acetyl-CoA that is used in the synthesis of ketone bodies. Once levels of fatty acids and ketones are high enough in the blood, muscle tissue will utilize fatty acids its major fuel and the brain will adapt to using ketones for energy. After several weeks of fasting, the brain derives approximately two-thirds of its energy from ketones and one-third from glucose. The shift from glucose to ketones as the major fuel reduces the amount of essential amino acids that must be degraded to support gluconeogenesis, which spares proteins that are vital for other functions. Cells that have few, if any, mitochondria, like red blood cells, continue to be dependent on glucose for their energy.

MCAT Concept Check 12.4:

Before you move on, assess your understanding of the material with these questions.

1. Provide an example of disequilibrium that is maintained at the expense of cellular energy.

2. What tissue is least able to change its fuel source in periods of prolonged starvation?

3. During what stage is there the greatest decrease in the circulating concentration of insulin?