Chapter 14: Metabolism of Macronutrients

Using Macronutrients in Metabolism

Metabolism consists of all the chemical processes that occur in living cells. These processes are classified as either anabolic or catabolic. Anabolic means to build; anabolic reactions require energy, just as it take energy to build a house. Catabolic means to break down; catabolic reactions break large molecules, such as in food, into smaller pieces. In the body, catabolic reactions release the energy that is in food so that it can be used by our cells. If you have trouble remembering the difference between the two, remember that anabolic steroids are used to build enormous muscle mass.

 

Because catabolic reactions produce energy and anabolic reactions use energy, a body in energy balance uses the same amount of energy that it produces. If the body’s catabolic reactions release more energy than the anabolic reactions use, the body stores the excess energy by building glycogen or fat molecules for long-term storage. On the other hand, if the net energy change is negative (catabolic reactions release less energy than anabolic reactions use), the body uses stored energy. This is shown in the example below of glucose and glycogen. The same is true for other macronutrients.

Catabolic processes are common in the digestion of nutrients and in the production of cellular energy. Anabolic processes are used to take the building blocks from our diet and build up our macromolecules.

Catabolism

All three classes of macronutrients can be broken down and used to produce ATP, the cellular form of energy. Of the three macronutrients, carbohydrates are considered the most common source of body fuel. Carbohydrates include complex carbohydrates such as starch and glycogen, and simple sugars (monosaccharides and disaccharides) including glucose, fructose, and sucrose. Carbohydrate catabolism breaks polysaccharides into monosaccharides. The monosaccharides glucose is the most common fuel for ATP production in cells; numerous endocrine control mechanisms regulate its concentration in the bloodstream. Excess glucose is either stored as an energy reserve in the liver and skeletal muscles as the complex polysaccharide 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 amino acids (monomers). Amino acids can be used as building blocks of new proteins or broken down further for the production of ATP. During starvation or when the diet is too low in protein, amino acids from proteins in the body can be used for energy, which leads to muscle loss and body wasting.

Nucleic acids are present in most the foods. 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 cells.

Anabolism

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 that comes from ATP molecules previously generated by catabolic reactions. Anabolic reactions, also called biosynthesis reactions, create new molecules that form new cells and tissues, and revitalize organs.

Anabolic reactions are often used to create storage forms of energy. Examples include glycogenosis which forms glycogen from excess glucose for storage in liver and muscles as well as storage of excess fatty acids and glycerol in the adipose tissue as triglycerides.

Interconversion of Macromolecules

The metabolic pathways for glucose, amino acids, and lipids are connected through glycolysis, pyruvate oxidation and the citric acid cycle. All steps in these pathways are bidirectional allowing the same enzymes that break glucose down during glycolysis to be used to synthesis glucose from intermediates in the citric acid cycle or pyruvate. This allows excess glucose to end up stored as triglycerides in adipose tissue, a process known as lipogenesis, or proteins to be used to synthesize glucose in the liver, a process known as gluconeogenesis. These reactions are summarized in figure 14.4, below.

Amino acids must be deaminated before entering these pathways, and where a particular amino acid enters depends upon the R group or side chain present. Some can enter as pyruvate, as acetyl CoA, or parts of the citric acid cycle.

As fatty acids are broken down, they enter as acetyl CoA. It is important to note that although glucose can be converted to fatty acids and later triglycerides, fatty acids cannot be used to produce glucose. The glycerol from a triglyceride, however, does enter glycolysis and can be used for gluconeogenesis.

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 is the breakdown of food 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 last for up to four hours. The rise in glucose concentrations in the bloodstream stimulates 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. Insulin also promotes the synthesis of protein in muscle. 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. Figure 14.5 summarizes the metabolic processes occurring in the body during the absorptive state.

 

Phenylketonuria: an example disorder of amino acid metabolism

Phenylketonuria (PKU) is a genetic disorder with a mutation in the enzyme phenylalanine hydroxylase. People with PKU are unable to break down the amino acid phenylalanine, resulting in toxic levels in the body. This results in damage to the central nervous system and brain. Symptoms include delayed neurological development, hyperactivity, mental retardation, seizures, skin rash, tremors, and uncontrolled movements of the arms and legs. Infants born in the United States and Canada are tested for PKU. A person diagnosed with PKU must follow a strict diet low in phenylalanine. The earlier a modified diet is begun, the less severe the symptoms will be. Pregnant women with PKU who are not on controlled diets are at a high risk for exposing the fetus to too much phenylalanine, which can cross the placenta and affect fetal development. Babies exposed to excess phenylalanine in utero may have heart defects, physical and/or mental retardation, and microcephaly. Some animal products and certain starches are also high in phenylalanine, and intake of these foods should be carefully monitored. The synthetic sweetener aspartame produces phenylalanine when metabolized in the body, so people with PKU avoid it as well.

The Postabsorptive 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 relies 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. 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.

 

Starvation

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, an alternative fuel made in the liver from stored fatty acids, to satisfy the energy needs of the brain and other glucose-dependent organs, and to maintain proteins in the cells. 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. Fatty acids and triglyceride stores are used to create ketones for the body. This prevents breakdown of proteins, but as fat stores are 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.

Hormonal Regulation of Metabolism

Catabolic and anabolic hormones in the body help regulate metabolic processes. Catabolic hormones which stimulate the breakdown of molecules and the production of energy include cortisol, glucagon, adrenaline/epinephrine, and cytokines. These hormones are mobilized at specific times to meet the needs of the body. Anabolic hormones required for the synthesis of molecules include growth hormone, insulin-like growth factor, and insulin.

Table 14.1 Catabolic Hormones

Hormone	Function
Cortisol	Released from the adrenal gland in response to stress; its main role is to increase blood glucose levels by gluconeogenesis (breaking down fats and proteins)
Glucagon	Released from alpha cells in the pancreas either when starving or when the body needs to generate additional energy; it stimulates the breakdown of glycogen in the liver to increase blood glucose levels; its effect is the opposite of insulin; glucagon and insulin are a part of a negative-feedback system that stabilizes blood glucose levels
Adrenaline/epinephrine	Released in response to the activation of the sympathetic nervous system; increases heart rate and heart contractility, constricts blood vessels, is a bronchodilator that opens (dilates) the bronchi of the lungs to increase air volume in the lungs, and stimulates gluconeogenesis

Table 14.2 Anabolic Hormones

Hormone	Function
Growth hormone (GH)	Synthesized and released from the pituitary gland; stimulates the growth of cells, tissues, and bones
Insulin-like growth factor (IGF)	Stimulates the growth of muscle and bone while also inhibiting cell death (apoptosis)
Insulin	Produced by the beta cells of the pancreas; plays an essential role in carbohydrate and fat metabolism, controls blood glucose levels, and promotes the uptake of glucose into body cells; causes cells in muscle, adipose tissue, and liver to take up glucose from the blood and store it in the liver and muscle as glycogen; its effect is the opposite of glucagon; glucagon and insulin are a part of a negative-feedback system that stabilizes blood glucose levels

Attributions

Adapted by Pattie S. Green, Ph.D. and Jonathan E. Pottle, Ph.D. at Tacoma Community College from the following sources:

• Anatomy and Physiology., “Metabolic States of the Body,” OpenStax CNX. January 27, 2022, shared under CC-BY-4.0
• Kansas State University Human Nutrition Flexbook, “Integration of Macronutrient and Alcohol Metabolism”, by Lindshield, B. L. (2018), shared under CC BY-NC-SA 4.0