You eat periodically throughout the day; however, your organs, especially the brain, need a continuous supply of glucose. How does the body meet this constant demand for energy? Your body processes the food you eat both to use immediately and, importantly, to store as energy for later demands. If there were no method in place to store excess energy, you would need to eat constantly in order to meet energy demands. Distinct mechanisms are in place to facilitate energy storage, and to make stored energy available during times of fasting and starvation.

Overview

There are three main metabolic states of the body: absorptive (fed), postabsorptive (fasting), and starvation. During any given day, your metabolism switches between absorptive and postabsorptive states. Starvation states happen very rarely in generally well-nourished individuals. When the body is fed, glucose, fats, and proteins are absorbed across the intestinal membrane and enter the bloodstream and lymphatic system to be used immediately for fuel. Any excess is stored for later fasting stages. As blood glucose levels rise, the pancreas releases insulin to stimulate the uptake of glucose by hepatocytes in the liver, muscle cells/fibers, and adipocytes (fat cells), and to promote its conversion to glycogen. As the postabsorptive state begins, glucose levels drop, and there is a corresponding drop in insulin levels. Falling glucose levels trigger the pancreas to release glucagon to turn off glycogen synthesis in the liver and stimulate its breakdown into glucose. The glucose is released into the bloodstream to serve as a fuel source for cells throughout the body. If glycogen stores are depleted during fasting, alternative sources, including fatty acids and proteins, can be metabolized and used as fuel. When the body once again enters the absorptive state after fasting, fats and proteins are digested and used to replenish fat and protein stores, whereas glucose is processed and used first to replenish the glycogen stores in the peripheral tissues, then in the liver. If the fast is not broken and starvation begins to set in, during the initial days, glucose produced from gluconeogenesis is still used by the brain and organs. After a few days, however, ketone bodies are created from fats and serve as the preferential fuel source for the heart and other organs, so that the brain can still use glucose. Once these stores are depleted, proteins will be catabolized first from the organs with fast turnover, such as the intestinal lining. Muscle will be spared to prevent the wasting of muscle tissue; however, these proteins will be used if alternative stores are not available.

The Absorptive State

The absorptive state, or the fed state, occurs after a meal when your body is digesting the food and absorbing the nutrients (anabolism exceeds catabolism). Digestion begins the moment you put food into your mouth, as the food is broken down into its constituent parts to be absorbed through the intestine. The digestion of carbohydrates begins in the mouth, whereas the digestion of proteins and fats begins in the stomach and small intestine. The constituent parts of these carbohydrates, fats, and proteins are transported across the intestinal wall and enter the bloodstream (sugars and amino acids) or the lymphatic system (fats). From the intestines, these systems transport them to the liver, adipose tissue, or muscle cells that will process and use, or store, the energy.

Depending on the amounts and types of nutrients ingested, the absorptive state can linger for up to 4 hours. The ingestion of food and the rise of glucose concentrations in the bloodstream stimulate pancreatic beta cells to release insulin into the bloodstream, where it initiates the absorption of blood glucose by liver hepatocytes, and by adipose and muscle cells. Once inside these cells, glucose is immediately converted into glucose-6-phosphate. By doing this, a concentration gradient is established where glucose levels are higher in the blood than in the cells. This allows for glucose to continue moving from the blood to the cells where it is needed. Insulin also stimulates the storage of glucose as glycogen in the liver and muscle cells where it can be used for later energy needs of the body. Insulin also promotes the synthesis of protein in muscle. As you will see, muscle protein can be catabolized and used as fuel in times of starvation.

If energy is exerted shortly after eating, the dietary fats and sugars that were just ingested will be processed and used immediately for energy. If not, the excess glucose is stored as glycogen in the liver and muscle cells, or as fat in adipose tissue; excess dietary fat is also stored as triglycerides in adipose tissues.

image summarizes the metabolic processes occurring in the body during the absorptive state.

The postabsorptive state, or the fasting state, occurs when the food has been digested, absorbed, and stored. You commonly fast overnight, but skipping meals during the day puts your body in the postabsorptive state as well. During this state, the body must rely initially on stored glycogen. Glucose levels in the blood begin to drop as it is absorbed and used by the cells. In response to the decrease in glucose, insulin levels also drop. Glycogen and triglyceride storage slows. However, due to the demands of the tissues and organs, blood glucose levels must be maintained in the normal range of 80–120 mg/dL. In response to a drop in blood glucose concentration, the hormone glucagon is released from the alpha cells of the pancreas. Glucagon acts upon the liver cells, where it inhibits the synthesis of glycogen and stimulates the breakdown of stored glycogen back into glucose. This glucose is released from the liver to be used by the peripheral tissues and the brain. As a result, blood glucose levels begin to rise. Gluconeogenesis will also begin in the liver to replace the glucose that has been used by the peripheral tissues.

After ingestion of food, fats and proteins are processed as described previously; however, the glucose processing changes a bit. The peripheral tissues preferentially absorb glucose. The liver, which normally absorbs and processes glucose, will not do so after a prolonged fast. The gluconeogenesis that has been ongoing in the liver will continue after fasting to replace the glycogen stores that were depleted in the liver. After these stores have been replenished, excess glucose that is absorbed by the liver will be converted into triglycerides and fatty acids for long-term storage. image summarizes the metabolic processes occurring in the body during the postabsorptive state.

When the body is deprived of nourishment for an extended period of time, it goes into “survival mode.” The first priority for survival is to provide enough glucose or fuel for the brain. The second priority is the conservation of amino acids for proteins. Therefore, the body uses ketones to satisfy the energy needs of the brain and other glucose-dependent organs, and to maintain proteins in the cells (see image). Because glucose levels are very low during starvation, glycolysis will shut off in cells that can use alternative fuels. For example, muscles will switch from using glucose to fatty acids as fuel. As previously explained, fatty acids can be converted into acetyl CoA and processed through the Krebs cycle to make ATP. Pyruvate, lactate, and alanine from muscle cells are not converted into acetyl CoA and used in the Krebs cycle, but are exported to the liver to be used in the synthesis of glucose. As starvation continues, and more glucose is needed, glycerol from fatty acids can be liberated and used as a source for gluconeogenesis.

After several days of starvation, ketone bodies become the major source of fuel for the heart and other organs. As starvation continues, fatty acids and triglyceride stores are used to create ketones for the body. This prevents the continued breakdown of proteins that serve as carbon sources for gluconeogenesis. Once these stores are fully depleted, proteins from muscles are released and broken down for glucose synthesis. Overall survival is dependent on the amount of fat and protein stored in the body.

Energy Consumed

Energy is another word for calories. What you eat and drink is "energy in." What you burn through physical activity is "energy out."

National Heart, Lung, and Blood Institute

Scientists use the term bioenergetics to discuss the concept of energy flow (image 1) through living systems, such as cells. Cellular processes such as building and breaking down complex molecules occur through stepwise chemical reactions. Some of these chemical reactions are spontaneous and release energy; whereas, others require energy to proceed. Just as living things must continually consume food to replenish what they have used, cells must continually obtain more energy to replenish that which the many energy-requiring chemical reactions that constantly take place use. All of the chemical reactions that transpire inside cells, including those that use and release energy, are the cell’s metabolism.

Carbohydrate Metabolism

Sugar (a simple carbohydrate) metabolism (chemical reactions) is a classic example of the many cellular processes that use and produce energy. Living things consume sugar as a major energy source, because sugar molecules have considerable energy stored within their bonds. The following equation describes the breakdown of glucose, a simple sugar:

C6H12O6+6O2→6CO2+6H2O+energyC6H12O6+6O2→6CO2+6H2O+energy

Consumed carbohydrates have their origins in photosynthesizing organisms like plants (image). During photosynthesis, plants use the energy of sunlight to convert carbon dioxide gas (CO₂) into sugar molecules, like glucose (C₆H₁₂O₆). Because this process involves synthesizing a larger, energy-storing molecule, it requires an energy input to proceed. The following equation (notice that it is the reverse of the previous equation) describes the synthesis of glucose:

6CO2+6H2O+energy→C6H12O6+6O26CO2+6H2O+energy→C6H12O6+6O2

During photosynthesis chemical reactions, energy is in the form of a very high-energy molecule scientists call ATP, or adenosine triphosphate. This is the primary energy currency of all cells. Just as the dollar is the currency we use to buy goods, cells use ATP molecules as energy currency to perform immediate work. The sugar (glucose) is stored as starch or glycogen. Energy-storing polymers like these break down into glucose to supply ATP molecules.

Solar energy is required to synthesize a glucose molecule during the photosynthesis reactions. In photosynthesis, light energy from the sun initially transforms into chemical energy that temporally stores itself in the energy carrier molecules ATP and NADPH (nicotinamide adenine dinucleotide phosphate). Photosynthesis later uses the stored energy in ATP and NADPH to build one glucose molecule from six molecules of CO₂. This process is analogous to eating breakfast in the morning to acquire energy for your body that you can use later in the day. Under ideal conditions, energy from 18 molecules of ATP is required to synthesize one glucose molecule during photosynthesis reactions. Glucose molecules can also combine with and convert into other sugar types. When an organism consumes sugars, glucose molecules eventually make their way into each organism's living cell. Inside the cell, each sugar molecule breaks down through a complex series of chemical reactions. The goal of these reactions is to harvest the energy stored inside the sugar molecules. The harvested energy makes high-energy ATP molecules, which perform work, powering many chemical reactions in the cell. The amount of energy needed to make one glucose molecule from six carbon dioxide molecules is 18 ATP molecules and 12 NADPH molecules (each one of which is energetically equivalent to three ATP molecules), or a total of 54 molecule equivalents required for synthesizing one glucose molecule. This process is a fundamental and efficient way for cells to generate the molecular energy that they require.

Metabolic Pathways

The processes of making and breaking down sugar molecules illustrate two types of metabolic pathways. A metabolic pathway is a series of interconnected biochemical reactions that convert a substrate molecule or molecules, step-by-step, through a series of metabolic intermediates, eventually yielding a final product or products. In the case of sugar metabolism, the first metabolic pathway synthesized sugar from smaller molecules, and the other pathway broke sugar down into smaller molecules. Scientists call these two opposite processes—the first requiring energy and the second producing energy—anabolic (building) and catabolic (breaking down) pathways, respectively. Consequently, building (anabolism) and degradation (catabolism) comprise metabolism.

Anabolic and Catabolic Pathways

Anabolic pathways require an input of energy to synthesize complex molecules from simpler ones. Synthesizing sugar from CO₂ is one example. Other examples are synthesizing large proteins from amino acid building blocks, and synthesizing new DNA strands from nucleic acid building blocks. These biosynthetic processes are critical to the cell's life, take place constantly, and demand energy that ATP and other high-energy molecules like NADH (nicotinamide adenine dinucleotide) and NADPH provide (image 3).

ATP is an important molecule for cells to have in sufficient supply at all times. The breakdown of sugars illustrates how a single glucose molecule can store enough energy to make a great deal of ATP, 36 to 38 molecules. This is a catabolic pathway. Catabolic pathways involve degrading (or breaking down) complex molecules into simpler ones. Molecular energy stored in complex molecule bonds release in catabolic pathways and harvest in such a way that it can produce ATP. Other energy-storing molecules, such as fats, also break down through similar catabolic reactions to release energy and make ATP (image 3).

It is important to know that metabolic pathway chemical reactions do not take place spontaneously. A protein called an enzyme facilitates or catalyzes each reaction step. Enzymes are important for catalyzing all types of biological reactions—those that require energy as well as those that release energy.

Catabolic Reactions

Catabolic reactions break down large organic molecules into smaller molecules, releasing the energy contained in the chemical bonds. These energy releases (conversions) are not 100 percent efficient. The amount of energy released is less than the total amount contained in the molecule. Approximately 40 percent of energy yielded from catabolic reactions is directly transferred to the high-energy molecule adenosine triphosphate (ATP). ATP, the energy currency of cells, can be used immediately to power molecular machines that support cell, tissue, and organ function. This includes building new tissue and repairing damaged tissue. ATP can also be stored to fulfill future energy demands. The remaining 60 percent of the energy released from catabolic reactions is given off as heat, which tissues and body fluids absorb.

Structurally, ATP molecules consist of an adenine, a ribose, and three phosphate groups (Image). The chemical bond between the second and third phosphate groups, termed a high-energy bond, represents the greatest source of energy in a cell. It is the first bond that catabolic enzymes break when cells require energy to do work. The products of this reaction are a molecule of adenosine diphosphate (ADP) and a lone phosphate group (P_i). ATP, ADP, and P_i are constantly being cycled through reactions that build ATP and store energy, and reactions that break down ATP and release energy.

The energy from ATP drives all bodily functions, such as contracting muscles, maintaining the electrical potential of nerve cells, and absorbing food in the gastrointestinal tract. The metabolic reactions that produce ATP come from various sources (image).

Of the four major macromolecular groups (carbohydrates, lipids, proteins, and nucleic acids) that are processed by digestion, carbohydrates are considered the most common source of energy to fuel the body. They take the form of either complex carbohydrates, polysaccharides like starch and glycogen, or simple sugars (monosaccharides) like glucose and fructose. Sugar catabolism breaks polysaccharides down into their individual monosaccharides. Among the monosaccharides, glucose is the most common fuel for ATP production in cells, and as such, there are a number of endocrine control mechanisms to regulate glucose concentration in the bloodstream. Excess glucose is either stored as an energy reserve in the liver and skeletal muscles as the complex polymer glycogen, or it is converted into fat (triglyceride) in adipose cells (adipocytes).

Among the lipids (fats), triglycerides are most often used for energy via a metabolic process called β-oxidation. About one-half of excess fat is stored in adipocytes that accumulate in the subcutaneous tissue under the skin, whereas the rest is stored in adipocytes in other tissues and organs.

Proteins, which are polymers, can be broken down into their monomers, individual amino acids. Amino acids can be used as building blocks of new proteins or broken down further for the production of ATP. When one is chronically starving, this use of amino acids for energy production can lead to a wasting away of the body, as more and more proteins are broken down.

Nucleic acids are present in most of the foods you eat. During digestion, nucleic acids including DNA and various RNAs are broken down into their constituent nucleotides. These nucleotides are readily absorbed and transported throughout the body to be used by individual cells during nucleic acid metabolism.

In contrast to catabolic reactions, anabolic reactions involve the joining of smaller molecules into larger ones. Anabolic reactions combine monosaccharides to form polysaccharides, fatty acids to form triglycerides, amino acids to form proteins, and nucleotides to form nucleic acids. These processes require energy in the form of ATP molecules generated by catabolic reactions. Anabolic reactions, also called biosynthesis reactions, create new molecules that form new cells and tissues, and revitalize organs.