Metabolism is defined as the sum of all chemical reactions required to support cellular function and hence, the life of an organism. Metabolism is either categorized as catabolism, referring to all metabolic processes involved in molecule breakdown, or anabolism, which includes all metabolic processes involved in building bigger molecules. Generally, catabolic processes release energy and anabolic processes consume energy.  The reactions governing the breakdown of food to obtain energy are called catabolic reactions. Conversely, anabolic reactions use the energy produced by catabolic reactions to synthesize larger molecules from smaller ones, such as when the body forms proteins by stringing together amino acids. Both sets of reactions are critical to maintaining life.^[1]

The overall goals of metabolism are energy transfer and matter transport. Energy is transformed from food macronutrients into cellular energy, which is used to perform cellular work.  Metabolism transforms the matter of macronutrients into substances a cell can use to grow and reproduce, and also into waste products. For example, enzymes are proteins and their job is to catalyze chemical reactions. Catalyze means to speed up a chemical reaction and reduce the energy required to complete the chemical reaction, without the catalyst itself being used up in the reaction. Without enzymes, chemical reactions would not happen at a fast enough rate and would use up too much energy for life to exist. A metabolic pathway is a series of enzyme-catalyzed reactions that transform the starting material (known as a substrate) into intermediates, which are the substrates for subsequent enzymatic reactions in the pathway, until, finally, an end product is synthesized by the last enzymatic reaction in the pathway. Some metabolic pathways are complex and involve many enzymatic reactions, while others involve only a few chemical reactions.

To ensure cellular efficiency, the metabolic pathways involved in catabolism and anabolism are regulated in concert by energy status, hormones, and substrate and end-product levels. The concerted regulation of metabolic pathways prevents cells from inefficiently building a molecule when it is already available. Just as it would be inefficient to build a wall at the same time as it is being broken down, it is metabolically inefficient for a cell to synthesize fatty acids and break them down at the same time.

Catabolism of food molecules begins when food enters the mouth, as the enzyme salivary amylase initiates the breakdown of the starch in foods. The entire process of digestion converts the large polymers in food to monomers that can be absorbed. Starches are broken down into monosaccharides, lipids are broken down into fatty acids, and proteins are broken down into amino acids. These monomers are absorbed into the bloodstream either directly, as is the case with monosaccharides and amino acids, or repackaged in intestinal cells for transport by an indirect route through lymphatic vessels, as is the case with most fatty acids and other fat-soluble molecules.

Once absorbed, water-soluble nutrients first travel to the liver, which controls their passage into the blood, allowing the nutrients to be transported throughout the body. The fat-soluble nutrients gradually pass from the lymphatic vessels into the blood flowing to body cells. Cells requiring energy or building blocks take up the nutrients from the blood and process them in either catabolic or anabolic pathways. Our organ systems require fuel and building blocks to perform the many functions of the body, such as digesting, absorbing, breathing, pumping blood, transporting nutrients in and wastes out, maintaining body temperature, and making new cells.

Energy metabolism refers more specifically to the metabolic pathways that release or store energy. Some of these are catabolic pathways, like glycolysis (the splitting of glucose), β-oxidation (fatty-acid breakdown), and amino acid catabolism. Others are anabolic pathways and include those involved in storing excess energy (such as glycogenesis) and synthesizing triglycerides (lipogenesis). Table 7.1 “Metabolic Pathways” summarizes some catabolic and anabolic pathways and their functions in energy metabolism.

ATP: The Energy Currency of the Cell

Catabolic reactions break down large organic molecules into smaller molecules, releasing the energy contained in the chemical bonds. 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 carry out future energy demands.

Structurally, ATP molecules consist of an adenine, a ribose, and three phosphate groups (Figure 7.3). The chemical bond between the second and third phosphate groups is termed a high-energy bond, which 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.  ^[2]

The molecule Adenosine triphosphate (ATP) is the energy molecule of the cell. During catabolic reactions, ATP is created and energy is stored until needed during anabolic reactions. 

Catabolism: The Breakdown

All cells are in tune with their energy balance.  When energy levels are high, cells build molecules and when energy levels are low, catabolic pathways are initiated to make 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 (Figure 7.4).^[3]

Catabolic reactions break down proteins into amino acids, lipids into fatty acids, and polysaccharides into monosaccharides. These building blocks are then used to synthesize molecules in anabolic reactions.

Glucose is the preferred energy source by most tissues, but fatty acids and amino acids also can be catabolized to release energy that can drive the formation of ATP.

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).^[4]

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.^[5]

Proteins, which are polymers, can be broken down into their monomers, which are 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^[6]

The catabolism of nutrients to release energy can be separated into three stages, each containing individual metabolic pathways. The three stages of nutrient breakdown are the following:

1. Glycolysis for glucose, β-oxidation for fatty acids, or amino-acid catabolism
2. Citric Acid Cycle (or Krebs cycle)
3. Electron Transport Chain and ATP Synthesis

Anabolic Reactions: The Building

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, which are generated by catabolic reactions. Anabolic reactions, also called biosynthesis reactions, create new molecules that form new cells and tissues and revitalize organs.^[7]

The energy released by catabolic pathways powers anabolic pathways in building macromolecules such as the proteins RNA and DNA, and even entire new cells and tissues. Anabolic pathways are required to build new tissue, such as muscle, after prolonged exercise or the remodelling of bone tissue, a process involving both catabolic and anabolic pathways. Anabolic pathways also build energy-storage molecules, such as glycogen and triglycerides. Intermediates in the catabolic pathways of energy metabolism are sometimes diverted from ATP production and used as building blocks instead. This happens when a cell is in a positive-energy balance. For example, the citric-acid-cycle intermediate, α-ketoglutarate, can be anabolically processed to the amino acids, glutamate or glutamine, if they are required. The human body is capable of synthesizing eleven of the twenty amino acids that make up proteins. The metabolic pathways of amino acid synthesis are all inhibited by the specific amino acid that is the end-product of a given pathway. Thus, if a cell has enough glutamine, it turns off its synthesis.

Anabolic pathways are regulated by their end-products, but even more so by the energy state of the cell. When there is ample energy, bigger molecules, such as protein, RNA and DNA will be built as needed. Alternatively, when energy is insufficient, proteins and other molecules will be destroyed and catabolized to release energy. A dramatic example of this is seen in children with marasmus, a form of advanced starvation. These children have severely compromised bodily functions, often culminating in death by infection. Children with marasmus are starving for calories and protein, which are required to make energy and build macromolecules. The negative-energy balance in children with marasmus results in the breakdown of muscle tissue and tissues of other organs in the body’s attempt to survive. The large decrease in muscle tissue makes children with marasmus look emaciated or “muscle-wasted.”

Hunger and malnutrition were extremely prevalent in residential schools. The underfunding by the federal government resulted in poor quality and quantity of food being served to Indigenous children. A typical residential school diet consisted of severe caloric restrictions with very little fat and protein, insufficient fruits and vegetables, and common outbreaks of foodborne illnesses.^[8] These already malnourished children were then viewed as ideal candidates for nutrition experiments that further deprived them of essential minerals, vitamins, and nutrients.  The long-lasting effects of this malnourishment experienced by Indigenous children contributed to height stunting, a decreased basal metabolic rate, and increased susceptibility to obesity and chronic disease.^[9] Additionally, the effects of prolonged caloric restrictions experienced by Indigenous children likely resulted in the catabolism of proteins and other muscle tissues. Due to an inadequate dietary intake of fats or carbohydrates, proteins were catabolized in the body’s attempt to survive, increasing the risk of compromised health and bodily function among Indigenous children.

Energy Storage

In the “fed” state (when energy levels are high), extra energy from nutrients will be stored. Glucose is stored mainly in muscle and liver tissues. In these tissues, it is stored as glycogen, a highly branched macromolecule consisting of thousands of glucose molecules held together by chemical bonds. The glucose molecules are joined together by an anabolic pathway called glycogenesis. For each molecule of glucose stored, one molecule of ATP is used. Therefore, it costs energy to store energy. Glycogen levels do not take long to reach their physiological limit, and when this happens, excess glucose will be converted to fat. A cell in positive-energy balance detects a high concentration of ATP and acetyl-CoA produced by catabolic pathways. In response, the rate of catabolism is either slowed or shut off and the synthesis of fatty acids, which occurs by an anabolic pathway called lipogenesis, is turned on. The newly made fatty acids are transported to fat-storing cells called adipocytes where they are stored as triglycerides. Fat is a better alternative to glycogen for energy storage as it is more compact (per unit of energy) and, unlike glycogen, the body does not store water along with fat. Water weighs a significant amount, and increased glycogen stores, which are accompanied by water, would dramatically increase body weight. When the body is in positive-energy balance, excess carbohydrates, lipids, and protein can all be metabolized to fat, through a process known as lipogenesis.

A person is also in a negative-energy balance between meals. During this time, blood glucose levels start to drop. To restore blood glucose levels to their normal range, the anabolic pathway known as gluconeogenesis is stimulated. Gluconeogenesis is the process of building glucose molecules mostly from certain amino acids (but also from glycerol) and it occurs primarily in the liver (Figure 7.5 “Metabolic pathway of gluconeogenesis”). The liver exports the synthesized glucose into the blood for other tissues to use.