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Research Newsletter-Spring/Summer 2013

Giana Angelo, Ph.D.


Giana Angelo, Ph.D.
LPI Research Associate
Micronutrient Information Center

The word “metabolism” commonly appears in nutrition news, but what does it actually mean? The term encompasses so many concepts that entire textbooks are written about it, while research laboratories devote their full effort to studying just one aspect of metabolism.


The dictionary defines metabolism as the sum of the processes in the build-up and destruction of protoplasm. There are three key concepts included in this definition:

  • Protoplasm is the mixture of organic and inorganic substances that constitute the living cell.
  • Anabolism is the build-up of protoplasm. It involves a series of chemical reactions to construct molecules from smaller units.
  • Catabolism is the destruction of protoplasm. It involves a series of chemical reactions that break down molecules into smaller units.

Also important in this definition is the cell, the basic unit of life. Our bodies are a mixture of cells and proteins organized into complex structures like tissues and organs. Meanwhile, food is a complex mixture of atoms (the basic unit of matter) and molecules. So when we eat, we are providing both our bodies and our cells the materials necessary to support metabolism.

Energy Metabolism

You may hear people bemoaning their “slow metabolism” and how it foils their attempts to lose weight. In this context, one is referring to energy metabolism—all of the biochemical processes that convert food into useable energy and material. Energy metabolism can be further described at the whole-body and cellular levels.

Whole-body Metabolism

Whole-body metabolism refers to the sum of all metabolic reactions in the body and is represented by a very simple equation known as the energy balance equation:

Energy intake = Energy expenditure

Energy intake comes from the calories in the food we eat; specifically, from the calories in the macronutrients: carbohydrate provides 4 kilocalories (kcal) per gram (g), fat provides 9 kcal/g, and protein provides 4 kcal/g. Note that in nutrition, calorie and kilocalorie are used interchangeably to denote the energy content of food. Technically, a calorie is the amount of energy required to raise the temperature of one gram of water by one degree Celsius.

The expenditure side of the equation is comprised of three variables: basal metabolic rate (BMR), physical activity, and the thermic effect of food (TEF).

BMR represents the energy expended to maintain fundamental functions of the body. BMR is the largest contributor to total energy expenditure with 60-75% of our total energy output fueling basic activities of life, such as respiration, circulation, body temperature regulation, and synthesis of new cells and tissues. BMR itself is influenced by several factors, including body composition, age, gender, and genetics.

  • Body composition. Lean body mass (LBM) is the primary determinant of BMR. The more lean tissue (muscle tissue without fat) you have, the higher your BMR.
  • Age. There is a 3-5% decrease in BMR per decade of life after age 30. This is largely attributed to the loss of LBM that occurs with age.
  • Gender. BMR is higher in men than women.
  • Genetics. Inherited differences in genes (e.g., the FTO gene variant linked to obesity) and hormones (e.g., thyroid hormone) that participate in the regulation of metabolic pathways can influence BMR.

Physical activity accounts for 15-35% of total energy expenditure. Physical activity encompasses all types of muscle movement; thus, dedicated exercise sessions as well as daily activities like walking constitute physical activity. Not only does physical activity itself expend energy, but it can also increase LBM and, consequently, one’s BMR.

TEF represents the energy expended to digest, absorb, transport, metabolize, and store food. Five to ten percent of total energy expenditure goes to TEF. Some diet fads will encourage consumption of certain types of “calorie-burning” foods because it is energetically costly to process them with slightly higher TEF values. The contribution of an individual food to total energy expenditure is very small; it is much more effective to increase physical activity and decrease calorie intake for weight loss (for example, a 500 kcal/day imbalance will result in a weight loss of one pound per week) and to reap a myriad of health benefits.

Metabolic disorders. Metabolic syndrome is a composite of metabolic disturbances that increase one’s risk for developing cardiovascular disease and type 2 diabetes. The risk for developing metabolic syndrome itself is closely linked to obesity and lack of physical activity, both of which contribute to a chronic imbalance in whole-body energy metabolism. The pathophysiological causes and effects of metabolic syndrome are not yet fully known. It appears that abdominal adiposity and insulin resistance are the most critical risk factors leading to its development. Inflammation may also be an important contributor. Please visit the Disease Index in LPI’s online Micronutrient Information Center (MIC) and the Cardiovascular and Metabolic Diseases (CMD) research group for more information on metabolic syndrome.

Cellular Metabolism

During digestion, food is broken down into its constituent molecules, which are absorbed into the blood stream and then presented to the cell. Carbohydrates consist of molecules of glucose and fructose, dietary fat (primarily in the form of triglycerides) contains three fatty acid molecules attached to a glycerol molecule, and proteins are built of linked amino acid molecules.

Once inside the cell, energy metabolism relies on an organelle known as the mitochondrion (see figure below). The mitochondria are often referred to as the “power plants” of the cell because they convert the chemical energy in food to a form of usable energy known as adenosine triphosphate (ATP). ATP must be constantly generated in order to fuel all of the fundamental processes that comprise BMR.

Macronutrient and Micronutrient Metabolism

Nutrients are the chemicals in food that are essential to human growth and function. They are generally divided into two major classes: the macronutrients and the micronutrients. In terms of energy metabolism, the macronutrients provide chemical energy, while the micronutrients function as essential cofactors, or assistants, required for obtaining the energy provided by macronutrients. Micronutrients are so named because they are required only in very small amounts compared to macronutrients.

Macronutrient Metabolism

The macronutrients provide energy and the building blocks of large biological molecules like proteins and membrane lipids. A mixture of carbohydrates (starches and sugars) and fats are oxidized to maintain a constant supply of ATP to support daily activities and exercise. The proportion of each substrate used varies with the type and duration of physical activity. Carbohydrate is especially important for ATP production during exercise, while much of the energy used during rest comes from fat. Though dietary protein provides calories, carbohydrate and fat are the preferred substrates for energy metabolism, sparing protein for other vital bodily functions. The body can use protein as an energy source during illness, trauma, and when stores of carbohydrate and fat are low, but this limits the availability of protein for essential basal metabolic requirements.

Micronutrient Metabolism

Micronutrients do not directly provide energy; rather, they assist in the acquisition of energy provided by the macronutrients.

B vitamins. The B vitamins in particular serve an important role as cofactors in energy metabolism. Energy metabolism consists of a series of enzymatic reactions that convert the molecules in food to ATP. Enzymes do not work in isolation—they require several vitamins to help them carry out the metabolic reactions. Each of the B vitamins (thiamin, riboflavin, niacin, pantothenic acid, vitamin B6, biotin, folate, and vitamin B12) serves as a cofactor in various aspects of carbohydrate, fat, and protein metabolism.

Because the enzymatic reaction requires B-vitamin cofactors, deficiency in one or more B vitamins could restrict the rate of the reaction, becoming a “rate-limiting” factor. The Dietary Reference Intakes (DRIs) are intake recommendations for healthy individuals, designed to prevent deficiency disease and to reduce the risk of chronic disease when sufficient scientific evidence exists. The recommended intakes for the B vitamins are set at levels to maintain sufficient plasma concentrations and to ensure optimal activity of the enzymatic reactions in which they participate.

Lipoic acid, L-carnitine, and coenzyme Q10. In addition to the B vitamins, several other nutrients operate in energy metabolism. Lipoic acid, L-carnitine, and coenzyme Q10 are conditionally essential nutrients that can be synthesized inside our bodies and obtained from foods and dietary supplements. Each participates in different aspects of cellular energy metabolism inside mitochondria (see figure below).

  • Lipoic acid. Alpha-lipoic acid is derived from a short-chain fatty acid precursor and contains two thiol (sulfur-containing) groups, important for the functional activity of lipoic acid. Lipoic acid is incorporated into the structure of several enzymes involved in cellular energy metabolism and serves as a critical functional group in the oxidation of macronutrient-derived substrates. While protein-bound lipoic acid functions in energy metabolism, free lipoic acid can function as an antioxidant, a metal-chelator, and in glucose uptake and utilization.
  • L-carnitine. Carnitine, chemically derived from the amino acids lysine and methionine, is necessary for the transport of long-chain fatty acids into the mitochondria. In healthy people, carnitine balance is maintained throughendogenous biosynthesis of L-carnitine, absorption from dietary sources, and elimination and reabsorption by the kidneys. Nutritional carnitine deficiency is very rare, but the potential benefits of carnitine supplementation in humans is an active area of research.
  • Coenzyme Q10. Coenzyme Q10 is a fat-soluble compound and integral component of the electron transport chain (ETC) inside mitochondria. The ETC is a series of steps by which electrons are transferred between complexes embedded within the inner matrix of mitochondria. It is via the ETC that our cells couple the oxidation of the molecules in food to the generation of energy as ATP.

Dr. Tory Hagen, the director of LPI’s Healthy Aging Program, has termed lipoic acid and acetyl-L-carnitine “age-essential” micronutrients and is investigating their ability to counteract mitochondrial dysfunction that occurs as we age. Acetyl-L-carnitine has an added acetyl group and is better absorbed and better distributed in the body than L-carnitine. For more information about lipoic acid, acetyl-L-carnitine, and coenzyme Q10, please visit the “Other Nutrients” section in our Micronutrient Information Center (MIC).

metabolism figure

Other Types of Metabolism

Xenobiotic metabolism. While energy metabolism involves the conversion of dietary molecules to usable cellular energy, xenobiotic metabolism involves the conversion of foreign molecules to manageable forms. More specifically, xenobiotic metabolism involves a series of enzymatic reactions that convert a foreign chemical compound (the prefix “xeno” means stranger) into an inert substance that can be safely excreted from the body. It can be divided into three phases. In phase I, also referred to as activation, oxygen is used to form a reactive site on the xenobiotic compound; members of the cytochrome P450(CYP) family of enzymes participate in phase I metabolism. Phase II, or conjugation, involves the addition of a water-soluble chemical group to the reactive site of the phase I metabolite. And finally, in phase III, the solubilized compound is expelled from the cell and then excreted from the body.

Drugs, toxins, steroid hormones, and carcinogens are substrates for enzymes involved in xenobiotic metabolism. One of the ways certain phytochemicals (non-nutrient plant chemicals found in fruits and vegetables) may benefit health is by inducing or inhibiting enzymes involved in xenobiotic metabolism. For example, animal studies demonstrate that metabolites of indole-3-carbinol (I3C), a compound present in cruciferous vegetables, can induce the expression of various phase I and phase II enzymes, potentially enhancing the detoxification and elimination of carcinogens.

By this same mechanism, certain phytochemicals may interact with prescribed medications that share xenobiotic (or biotransformation) enzymes, potentially altering the effective dose of the drug. As always, it is important to inform your healthcare provider of any dietary supplements you are taking.

First-pass metabolism. First-pass metabolism is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation due to action in the gastrointestinal tract and liver. The amounts of drugs prescribed account for first-pass effects so that a sufficient amount of active agent will reach the target tissue. Phytochemicals are also subjected to first-pass metabolism. As a result, the form of the phytochemical in circulation is very different from that of the ingested compound. Therefore, it’s very important to recognize that the health effects of many phytochemicals are likely due to their metabolites and not to the parent compound found in food.


Stated very simply, metabolism is a biochemical conversion. We convert food to ATP (energy metabolism), we convert medications to inert compounds (xenobiotic metabolism), and we convert plant chemicals to various bioactive forms (first-pass metabolism). Each metabolic reaction requires the coordinated activity of several proteins, enzymes, and cofactors, all of which rely on proper and adequate nutrient intake for optimal function.

This article has touched on only a few basic concepts of metabolism and is by no means comprehensive. Please see the MIC for more detailed information on each of the micronutrients mentioned above.

Last updated May 2013