Metabolism

In metabolic activity, the two major chemical reactions are catabolism and anabolism. Catabolism is splitting complex substances into simpler substances; anabolism is using absorbed nutrients to build or synthesize more complex compounds (see Chapter 2 or online at Evolve for more detail). Anabolism and catabolism are continuous reactions in the body. Cells in the epithelial lining of the oral and gastrointestinal mucosa are replaced approximately every 3 to 7 days. Despite this rapid turnover, the rate of catabolism is usually equal to that of anabolism in a healthy adult. During certain stages of life, such as growth periods or pregnancy, more anabolism is occurring than catabolism. Conversely, when illness or stress occurs, excessive catabolism is evident.

Other phases of metabolism include delivery of nutrients to the cells where they are needed, and delivery of wastes to sites where they can be excreted. After absorption of the macronutrients, glucose, fatty acids, and amino acids can be used to yield energy via a common pathway within the mitochondria of cells (Fig. 7-1). The catabolic end products of carbohydrates, proteins, and fats are carbon dioxide, water, and energy. Nitrogen is an additional end product of protein.

The Krebs cycle (also called citric acid cycle or tricarboxylic acid [TCA] cycle) converts glucose, fatty acids, and amino acids to a usable form of energy, requiring many enzymes. Additional information on the TCA cycle can be found in Chapter 2 and online at Evolve. For activation of some enzymes, vitamins or minerals or both must be available. An enzyme needing vitamins for activation is called a coenzyme. Thiamin, riboflavin, and niacin are B vitamins essential as coenzymes in the TCA cycle. An enzyme may also require a cofactor. A cofactor functions in the same way as coenzymes, but the molecule required is a mineral or electrolyte.

Anabolic processes require energy. Examples of anabolism are the building of new muscle tissue or bone and the secretion of cellular products such as hormones. Hormones are “messengers” produced by a group of cells that stimulate or retard the functions of other cells. Hormones principally control different metabolic functions that affect secretions and growth. Anabolism involves the use of glucose, amino acids, fatty acids, and glycerol to build various substances that make up the body itself and the other substances necessary for the body to function. All nutrients are intertwined in this process. For instance, dispensible amino acids are ordinarily used to build proteins, but glucose can be the basis for anabolism of amino acids and fatty acids.

Role of the Liver

The liver plays a major regulatory role by controlling the kinds and quantities of nutrients in the bloodstream. All monosaccharides are converted to glucose in the liver to provide an energy supply for the cells. Glycogen, a polysaccharide, also can be broken down to glucose and released into the circulating blood as needed. Other end products of digestion may be oxidized to provide energy; converted to glucose, protein, fat, or other substances; or released to circulate at prescribed levels in the blood for use by cells throughout the body.

Role of the Kidneys

Kidneys perform the important metabolic task of removing waste products from the blood, and along with the liver, control the levels of many nutrients in the blood. Metabolic end products from cells, unnecessary substances absorbed from the gastrointestinal tract, potentially harmful compounds that have been detoxified by the liver, and drugs are removed from the blood by the kidneys.

Kidneys accomplish this task by a process of filtration and reabsorption. Glucose, amino acids, vitamins, water, and various minerals are reabsorbed or excreted by the kidneys, depending on the body’s need. Excess nitrogen from protein catabolism also is excreted by the kidneys. Kidneys help maintain nutrient balance within the body. Other routes of excretion of waste products are through the bowel; the skin, which excretes water and electrolytes; and the lungs, which remove carbon dioxide and water.

Carbohydrate Metabolism

Monosaccharides are transported through the portal vein to the liver for glycogenesis, a process in which sugars, including fructose, galactose, sorbitol, and xylitol, may be stored as glycogen. Glucose is the circulating sugar in the blood; it is the major energy supply for cells. The level of circulating glucose is closely monitored by the liver and is constantly maintained at a normoglycemic level (normal blood glucose range), between 70 and 100 mg/dL. Insulin is a hormone that lowers blood glucose levels. Blood glucose levels peak at 140 mg/dL 30 to 60 minutes after a meal and return to normal within 3 hours in individuals with normal secretion and use of insulin. This consistent blood glucose level is significant, indicating the necessity of a certain amount of glucose in the blood for normal functioning of body tissues (Fig. 7-2). Hyperglycemia (elevated blood glucose) and hypoglycemia (decreased blood glucose) are very serious conditions that could be fatal; the precipitating cause for either should be identified. Many patients with diabetes who take insulin or an antidiabetic medication that can cause hypoglycemia, or both, may exhibit symptoms related to hypoglycemia, particularly if they have not eaten within a 4- to 5-hour time span. These patients need to be treated with a carbohydrate source before continuing treatment (see Health Application 7).

Individuals with diabetes often respond differently to different carbohydrate sources. It is important for patients with diabetes to closely manage and monitor their glycemic levels. The blood glucose response to different foods and different combinations of food cannot be accurately predicted from the amount of simple sugars or complex carbohydrates ingested.¹ White bread, potatoes, and white rice have a glycemic effect similar to sucrose. Glycemic effect is the rate at which glucose increases in the bloodstream after a particular food is eaten.

A complex hormonal system maintains a constant blood glucose level. Insulin is the primary hormone that lowers blood glucose levels. When hyperglycemia occurs, insulin is secreted to decrease blood glucose levels. Conversely, hypoglycemia elicits the secretion of several hormones (thyroid hormone, epinephrine, glucagon, and growth hormone) to increase blood glucose levels. The liver can elevate blood glucose levels by converting amino acids from protein, and glycerol from fats to glucose. The process of synthesizing glucose from noncarbohydrate sources is known as gluconeogenesis (see Chapter 2 or online at Evolve for additional details).

Dietary carbohydrates ensure optimal glycogen stores and are digested faster than other energy nutrients. The liver can degrade glycogen to glucose. The amount of energy available from glycogen stores is generally less than a day’s energy expenditure, or approximately 1200 to 1800 kcal. Red blood cells, and cells in the heart, brain, and renal medulla prefer glucose as their energy source.

Protein Metabolism

Amino acids are transported through the portal vein into the liver. The liver is an “aminostat,” monitoring the intake and breakdown of most of the amino acids. Individual amino acids are released by the liver to enter the general circulation at specific levels, so each amino acid is available as needed to synthesize each individual protein. Amino acids transported in the blood are rapidly removed for use by cells. If individual amino acids increase above a specific level in the blood, they are removed and oxidized for energy.

Protein metabolism is in a constant dynamic state, with catabolism and anabolism occurring continuously to replace worn-out proteins in cells. Even during anabolic periods such as growth, muscle catabolism is elevated as each cell remodels itself. Anabolic and catabolic processes are controlled by the liver and hormones. Insulin, thyroxine, and growth hormone stimulate protein synthesis.

Lipid Metabolism

Hormones involved in carbohydrate metabolism also control fat metabolism. Insulin increases fat synthesis, whereas thyroxine, epinephrine, growth hormone, and glucocorticoids increase fat mobilization. The liver is the principal regulator of fat metabolism and lipoprotein synthesis. Fatty acids can be hydrolyzed or modified by shortening, lengthening, or adding double bonds before their release from the liver into the circulation. The liver produces cholesterol, removes it from the blood, and uses it to make bile acid.

Metabolism of chylomicrons in the liver results in triglycerides being transported to the tissues for energy or other uses or carried to adipose tissue to be stored. Serum triglycerides are the result of not only absorption from foods, but also the conversion of carbohydrates and proteins into fats. Triglycerides can be synthesized in the intestinal mucosa, adipose tissue, and liver. Fats are synthesized in the process of lipogenesis and broken down during lipolysis (the splitting or decomposition of fat). These continual processes are in equilibrium when energy needs are balanced.

The process of hydrolyzing triglycerides into two-carbon entities to enter the Krebs cycle for energy production is known as oxidation. A discussion of oxidation can be found in Chapter 2 and online at Evolve. During oxidation, 1 lb of fat results in the release of 3500 kcal for energy—more than most individuals use in a 24-hour period. When excessive amounts of fats are oxidized for energy, the liver is overwhelmed, and acidic metabolic products, or ketones, are formed. Ketones are not oxidized in the liver, but are carried to the skeletal and cardiac muscles, where, under normal circumstances, they are rapidly metabolized.

If the glucose supply is reduced, the capacity of the tissues to use ketone bodies may be exceeded. Accumulation of ketone bodies in the body is known as ketosis. Ketosis may lead to ketoacidosis (acidic condition due to accumulation of large quantities of ketone bodies in the blood). The signs and symptoms of ketoacidosis include nausea, vomiting, and stomach pain. Ketoacidosis can be a dangerous condition for several reasons. Bases must neutralize these strong acids (ketones) to maintain acid-base balance in the blood. Ketones are excreted in the urine, a condition known as ketonuria, along with sodium. If adequate amounts of base are not available, acidosis may result. In addition to the loss of sodium ions, large amounts of water are lost, which can lead to dehydration (or rapid weight loss for an individual reducing caloric intake). When blood glucose levels remain low for several days, brain and nerve cells adapt to use ketones for some of their fuel requirements.

Carbohydrates play a predominant role in heavy exercise when the muscle’s oxygen supply is limited, but triglycerides provide about half the energy with continued exercise. Although fats can be stored as adipose tissue in virtually inexhaustible amounts, their slower rate of metabolism makes them a less efficient source of quick energy. The amount of energy available is highly variable in individuals, but usually at least 160,000 kcal is available from body fat stores.

Alcohol Metabolism

Although alcohol is considered a drug, the kilocalories it provides can be used by the body for energy, providing approximately 7 kcal/g. When consumed in excessive amounts, alcohol is a toxin. Caloric content of alcoholic beverages can be calculated by using the equations in Box 7-1. Alcoholic beverages contain negligible nutrients.

Alcohol is metabolized primarily by the liver. Alcohol provides an alternative fuel that is oxidized instead of fat; this may result in accumulation of lipids in the liver. Not much is known about safe amounts of alcohol consumption without risk of liver damage.

A well-balanced diet accompanied by habitual consumption of alcoholic beverages in excess of energy needs can be a risk factor for weight gain. However, excessive amounts of alcohol in a person who is an alcoholic tend to result in poor appetite for food and may lead to weight loss and malnutrition. In addition to causing liver damage, alcohol can interfere with the transport, activation, catabolism, and storage of almost every nutrient. Alcohol has a marked effect on blood pressure and risk of hypertension.²

The Dietary Guidelines advise moderation in alcohol consumption: one drink a day for women and no more than two drinks a day for men. (An alcoholic beverage is defined as 12 oz of regular beer, 5 oz of wine, or 1.5 oz of 80-proof distilled spirits.) For middle-aged and older adults, one to two drinks daily results in the lowest mortality rate.³ This is perhaps a result of the protective effects of moderate alcohol consumption on CHD. Alcohol consumption seems to provide little, if any, health benefit for younger individuals. Alcoholic beverages should be avoided by women who may become pregnant, are pregnant or breastfeeding.

Metabolic Interrelationships

The body is an overwhelmingly complex system. Whether excessive food intake is in the form of protein, carbohydrate, fat, or alcohol, most excess energy intake is stored as adipose tissue (Fig. 7-3). (Glycogen is another storage form of energy; however, the amount of glycogen stored in the body is limited.)

Protein from the metabolic pool of amino acids and in lean muscle mass is generally not considered a good source of energy, but it can be used for energy if caloric intake is below caloric expenditure. Fat is a good source of energy, but carbohydrate is the preferred fuel. However, the body cannot metabolize excessive quantities of fat without some side effects—ketoacidosis, hyperlipidemia, and accumulation of fat in the liver.

Carbohydrates can be used in forming nonessential amino acids. Proteins contribute to synthesis of some lipids (e.g., lipoproteins). Although lipids do not contribute significantly to the synthesis of amino acids, glycerol from triglycerides can be used for synthesis of carbohydrates. Fatty acids and some amino acids can be converted to glucose.

Catabolism of all classes of foodstuffs involves oxidation through the TCA cycle to produce energy. The quantity of kilocalories in the diet from carbohydrate or lipids influences protein metabolism. In some situations, one nutrient can be substituted for another because of their interrelationship. For example, a decrease in carbohydrate intake increases lipolysis; protein excess can be used for energy. Because the body can easily adapt to shifts in either carbohydrate or fat as the main source of energy, and in view of substantial body fat stores, large variations in macronutrient intake (energy sources) and energy expenditure are well tolerated.

In addition to energy-providing nutrients, vitamins and minerals are essential for digestion, absorption, and metabolism of carbohydrate, protein, and fat. Although vitamins and minerals are not required in the large quantities that macronutrients are, their presence is just as important. When a deficiency occurs, reactions do not proceed normally. For example, although protein may be consumed alone (as in liquid protein supplements), many other nutrients, including vitamins and minerals, must be present for the protein to be used by cells. Each nutrient has its specific function; all the nutrients must be present simultaneously for optimal benefits.

A detailed discussion of metabolic interrelationships is beyond the scope of this text. These interrelationships are important, and for optimal use of nutrients, food sources of all the nutrients should be consumed. The easiest way to obtain optimal nutrition is to include a variety of foods from all the food groups.

Metabolic Energy

Without energy from chemical reactions, people could not bat an eye, wiggle a toe, or think a thought. Energy is required for all physiological functions. Energy from food is converted into forms the body can use: electrical for the brain and nerves, mechanical for muscles, thermal for body heat, and chemical for synthesis of new compounds.

The potential energy value of foods and energy exchanges within the body are expressed in terms of the kilocalorie. A kilocalorie (kcal) is the amount of heat required to increase the temperature of 1 kg of water 1° C. A kilocalorie is 1000 times larger than the small calorie. Although kilocalorie is the proper term, it is commonly used interchangeably with calorie or Calorie (abbreviated Cal).

Carbohydrate, fat, protein, and even alcohol provide energy for humans. (Vitamins and minerals are not energy sources, but are necessary for energy-producing reactions.) Physiological energy values commonly used are 4 kcal/g carbohydrate, 9 kcal/g fat, 4 kcal/g protein, and 7 kcal/g alcohol.

Basal Metabolic Rate

Even during sleep, the body requires energy for the basic minimum tasks of respiration and circulation, and for many intricate activities within each cell. Basal metabolic rate (BMR) indicates the energy required for involuntary physiological functions to maintain life, including respiration, circulation, and maintenance of muscle tone and body temperature. The BMR is lowest while lying down, awake, rested, and relaxed in a comfortable environment, not having eaten for 12 to 15 hours. The BMR can be measured in a clinical setting using indirect calorimetry, which indirectly measures the rate of oxygen used while the person is resting (see Fig. 7-4). Because digestion and absorption require energy, the BMR is the amount of energy required when the body is in a postabsorptive state (digestion and absorptionare minimal).