Chapter 25:  Metabolism and Energetics

 

The term metabolism refers to all chemical reactions that occur in an organism.

 

Such functions include (1) metabolic turnover , the periodic breakdown and replacement of the organic components of a cell; (2) growth and cell division; and (3) special processes, such as secretion, contraction, and the propagation of action potentials.

 

The breakdown of organic substrates is called catabolism . This process releases energy that can be used to synthesize ATP or other high–energy compounds.

 

The ATP produced by mitochondria provides energy to support anabolism –the synthesis of new organic molecules as well as other cell functions.

 

In terms of energy, anabolism is an "uphill" (requires energy) process that involves the formation of new chemical bonds. Cells synthesize new organic components for four basic reasons:

 

To Perform Structural Maintenance or Repairs.

To Support Growth.

To Produce Secretions.

To Build Nutrient Reserves.

 

The nutrient pool (food) is the source of the substrates for both catabolism and anabolism.. In general, when a cell with excess carbohydrates, lipids, and amino acids needs energy, it will break down carbohydrates first. Lipids are the second choice, and amino acids are seldom broken down if other energy sources are available.

 

  Carbohydrate Metabolism

 

Most cells generate ATP and other high–energy compounds by breaking down carbohydrates–especially glucose.

 

The complete catabolism of one molecule of glucose will provide a typical cell in the body with a net gain of 36 molecules of ATP.

 

Although most of the actual ATP production occurs inside mitochondria, the first steps take place in the cytosol.

 

Glycolysis is the breakdown of glucose to pyruvic acid (pyruvate).

 

This anaerobic reaction sequence provides the cell with a net gain of two molecules of ATP for each glucose molecule converted to two pyruvic acid molecules.

 

Mitochondrial ATP Production

 

If oxygen supplies are adequate, mitochondria absorb the pyruvic acid molecules and break them down.

 

 

The TCA Cycle
The formation of citric acid from acetyl–CoA is the first step in a sequence of enzymatic reactions called the tricarboxylic acid (TCA) cycle , or citric acid cycle . This reaction sequence is sometimes called the Krebs cycle in honor of Hans Krebs, the biochemist who described the various reactions in 1937. The function of the cycle is to remove hydrogen atoms from organic molecules and transfer them to coenzymes.

 

Oxidative Phosphorylation and the Electron Transport System (ETS)
Oxidative phosphorylation is the generation of ATP within mitochondria in a reaction sequence that requires coenzymes and consumes oxygen. The process produces over 90 percent of the ATP used by our cells. The key reactions take place in the electron transport system (ETS) , a series of integral and peripheral proteins in the inner membrane of the mitochondrion.

 

The Electron Transport System The electron transport system (ETS) , or respiratory chain , is a sequence of proteins called cytochromes. Each cytochrome has two components: a protein and a pigment.

 

 

 

ATP Generation and the ETS

 

The electron transport system does not produce ATP directly. Instead, it creates the conditions necessary for ATP production by creating a steep concentration gradient across the inner mitochondrial membrane. The electrons that travel along the ETS release energy as they pass from coenzyme to cytochrome and from cytochrome to cytochrome. The energy released at several steps drives hydrogen ion pumps that move hydrogen ions from the mitochondrial matrix into the intermembrane space, between the inner and outer membranes of a mitochondrion. These pumps create a large concentration gradient for hydrogen ions across the inner membrane. It is this concentration gradient that provides the energy to convert ADP to ATP.

 

The Importance of Oxidative Phosphorylation Oxidative phosphorylation is the most important mechanism for the generation of ATP. In most cases, a chronic suspension, or even a significant reduction, of the rate of oxidative phosphorylation will kill the cell. If many cells are affected, the individual may die.

 

If the supply of oxygen is cut off, mitochondrial ATP production will cease, because reduced cytochrome will have no acceptor for its electrons. With the last reaction stopped, the entire ETS comes to a halt, like cars at a washed–out bridge. Oxidative phosphorylation can no longer take place, and cells quickly succumb to energy starvation. Because neurons have a high demand for energy, the brain is one of the first organs to be affected.


Hydrogen cyanide gas is sometimes used as a pesticide to kill rats or mice; in some states where capital punishment is legal, it is used to execute criminals. The cyanide ion binds to cytochrome and prevents the transfer of electrons to oxygen. As a result, cells die from energy starvation.

 

 

Gluconeogenesis  is the synthesis of glucose from noncarbohydrate precursors, such as lactic acid, glycerol, or amino acids. Fatty acids and many amino acids cannot be used for gluconeogenesis.

 

In the liver and in skeletal muscle, glucose molecules are stored as glycogen. The formation of glycogen from glucose, known as glycogenesis , is a complex process that involves several steps.  Glycogen is an important energy reserve that can be broken down when the cell cannot obtain enough glucose from interstitial fluid. The breakdown of glycogen, called glycogenolysis , occurs quickly and involves a single enzymatic step.

 

Lipid Metabolism

 

Like carbohydrates, lipid molecules contain carbon, hydrogen, and oxygen, but the atoms are present in different proportions. Triglycerides are the most abundant lipid in the body, so our discussion will focus on pathways for triglyceride breakdown and synthesis

 

Lipid Catabolism
During lipid catabolism, or lipolysis , lipids are broken down into pieces that can be either converted to pyruvic acid or channeled directly into the TCA cycle.

 

Lipids and Energy Production
Lipids are important as an energy reserve because they can provide large amounts of ATP. Since they are insoluble in water, lipids can be stored in compact droplets in the cytosol. This storage method saves space, but when the lipid droplets are large, it is difficult for water–soluble enzymes to get at them. Lipid reserves are therefore more difficult to access than carbohydrate reserves.

 

At rest (when energy demands are low), these cells break down fatty acids. During activity (when energy demands are large and immediate), skeletal muscle fibers shift to glucose metabolism.

 

Lipid Synthesis
The synthesis of lipids is known as lipogenesis. Linoleic acid and linolenic acid , both 18–carbon unsaturated fatty acids, cannot be synthesized. They are called essential fatty acids , because they must be included in your diet. Linoleic acid and linolenic acid are synthesized by plants. A deficiency of essential fatty acids generally occurs only among hospitalized individuals receiving nutrients in an intravenous solution. A diet poor in linoleic acid slows growth and alters the appearance of the skin.

 

Lipid Transport and Distribution
Like glucose, lipids are needed throughout the body. All cells require lipids to maintain their cell membranes, and important steroid hormones must reach target cells in many different tissues. Free fatty acids comprise a relatively small percentage of the total circulating lipids. Because most lipids are not soluble in water, special transport mechanisms carry them from one region of the body to another. Most lipids circulate through the bloodstream as lipoproteins.

 

•Cholesterol Has Many Vital Functions in the Human Body. Cholesterol serves as a waterproofing for the epidermis, a lipid component of all cell membranes, a key constituent of bile, and the precursor of several steroid hormones and one vitamin. Because cholesterol is so important, dietary restrictions should have the goal of keeping cholesterol levels within acceptable limits. The goal is not to eliminate cholesterol from the diet or from the circulating blood.

 

The Cholesterol Content of the Diet Is Not the Only Source of Circulating Cholesterol. The human body can manufacture cholesterol from the acetyl–CoA obtained through glycolysis or the beta–oxidation of other lipids. Dietary cholesterol probably accounts for only about 20 percent of the cholesterol in the bloodstream; the rest is the result of metabolism of saturated fats in the diet.

 

Cholesterol Levels Vary with Age and Physical Condition. At age 19, three out of four males have fasting cholesterol levels (levels measured 8–12 hours after a meal) below 170 mg/dl. Cholesterol levels in females of this age are slightly higher, typically at or below 175 mg/dl. As age increases, the cholesterol values gradually climb; over age 70, the values are 230 mg/dl (males) and 250 mg/dl (females). Cholesterol levels are considered unhealthy if they are higher than those of 90 percent of the population in that age group. For males, this value ranges from 185 mg/dl at age 19 to 250 mg/dl at age 70. For females, the comparable values are 190 mg/dl and 275 mg/dl, respectively.

 

For years, LDL:HDL ratios were taken to be valid predictors of the risk of developing atherosclerosis. Risk–factor analysis and LDL levels are now thought to be more accurate indicators. For males with more than one risk factor, many clinicians recommend dietary and drug therapy if LDL levels exceed 130 mg/dl, regardless of the total cholesterol or HDL levels.

 

Free Fatty Acids
Free fatty acids (FFAs) are lipids that can diffuse easily across cell membranes. Free fatty acids in the blood are generally bound to albumin, the most abundant plasma protein. Sources of free fatty acids in the blood include the following:

 

Fatty acids that are not used in the synthesis of triglycerides, but that diffuse out of the intestinal epithelium and into the blood.

 

Fatty acids that diffuse out of lipid stores, such as the liver and adipose tissue, when triglycerides are broken down.

Liver cells, cardiac muscle cells, skeletal muscle fibers, and many other body cells can metabolize free fatty acids, which are an important energy source during periods of starvation, when glucose supplies are limited.

 

Protein Metabolism

 

The body can synthesize 100,000 to 140,000 different proteins with various forms, functions, and structures. Yet, each protein contains some combination of the same 20 amino acids.

 

Amino Acid Catabolism
The first step in amino acid catabolism is the removal of the amino group This process requires a co–enzyme derivative of ( pyridoxine ). The amino group is removed by transamination or deamination.

 

Transamination attaches the amino group of an amino acid to a keto acid

Transamination converts the keto acid into an amino acid that can enter the cytosol and be used for protein synthesis. In the process, the original amino acid becomes a keto acid that can be broken down in the TCA cycle.

 

Deamination is performed in preparing an amino acid for breakdown in the TCA cycle.

 

Deamination is the removal of an amino group and a hydrogen atom in a reaction that generates an ammonia molecule or an ammonium ion. Ammonia molecules are highly toxic, even in low concentrations. Your liver, the primary site of deamination, has the enzymes needed to deal with the problem of ammonia generation. Liver cells convert the ammonia to urea , a relatively harmless water–soluble compound excreted in urine. The urea cycle is the reaction sequence involved in the production of urea

 

 

 

 

Proteins and ATP Production
Three factors make protein catabolism an impractical source of quick energy:

 

1.Proteins are more difficult to break apart than are complex carbohydrates or lipids.

 

2.One of the by–products, ammonia, is a toxin that can damage cells.

3.Proteins form the most important structural and functional components of any cell. Extensive protein catabolism therefore threatens homeostasis at the cellular and systems levels.

 

Protein Synthesis

 

There are 10 essential amino acids . Your body cannot synthesize eight of them (isoleucine , leucine , lysine , threonine , tryptophan , phenylalanine , valine , and methionine ); the other two ( arginine and histidine ) can be synthesized, but in amounts that are insufficient for growing children. Because the body can make other amino acids on demand, they are called the nonessential amino acids .

 

25–5  Nucleic Acid Metabolism  Cells contain both DNA and RNA.

The RNA in the cell is involved in protein synthesis, and RNA molecules are broken down and replaced regularly.

 

RNA Catabolism
In the breakdown of RNA, the bonds between nucleotides are broken and the molecule is disassembled into individual nucleotides. RNA catabolism makes a relatively insignificant contribution to the total energy budget of the cell.  Even when RNA is broken down, only the sugars and pyrimidines provide energy. The sugars can enter the glycolytic pathways. The purines (adenine and guanine) cannot be catabolized. Instead, they are deaminated and excreted as uric acid . Like urea, uric acid is a relatively nontoxic waste product, but it is far less soluble than urea. Urea and uric acid are called nitrogenous wastes , because they are waste products that contain nitrogen atoms.

 

At concentrations over 7.4 mg/dl, body fluids are saturated with uric acid. Although symptoms may not appear at once, uric acid crystals may begin to form in body fluids. The condition that then develops is called gout . Most cases of hyperuricemia and gout are linked to problems with the excretion of uric acid by the kidneys.

 

Nucleic Acid Synthesis
Most cells synthesize RNA; DNA synthesis occurs only in cells preparing for mitosis and cell division or for meiosis (nuclear events involved in gamete production).

 

 

Review pathways:

 

  Metabolic Interactions

 

The Liver. The liver is the focal point of metabolic regulation and control. Liver cells contain a great diversity of enzymes and so can break down or synthesize most of the carbohydrates, lipids, and amino acids needed by other body cells. Liver cells have an extensive circulatory supply, so they are in an excellent position to monitor and adjust the nutrient composition of circulating blood. The liver also contains significant energy reserves in the form of glycogen deposits.

 

Adipose Tissue. Adipose tissue stores lipids, primarily as triglycerides. Adipocytes are located in many areas; in previous chapters, we noted the presence of fat cells in areolar tissue, in mesenteries, within red and yellow marrows, in the epicardium, and around the eyes.

 

Skeletal Muscle. Skeletal muscle accounts for almost half of an individual's body weight, and skeletal muscle fibers maintain substantial glycogen reserves. In addition, their contractile proteins can be broken down and the amino acids used as an energy source if other nutrients are unavailable.

 

Neural Tissue. Neural tissue has a high demand for energy, but the cells do not maintain reserves of carbohydrates, lipids, or proteins. Neurons must be provided with a reliable supply of glucose, because they are generally unable to metabolize other molecules. If blood glucose levels become too low, neural tissue in the central nervous system cannot continue to function, and the individual falls unconscious.

 

Other Peripheral Tissues. Other peripheral tissues do not maintain large metabolic reserves, but they are able to metabolize glucose, fatty acids, or other substrates. Their preferred source of energy varies with the instructions provided by the endocrine system.

 

 

The Absorptive State
The absorptive state is the period following a meal, when nutrient absorption is under way. After a typical meal, the absorptive state continues for about 4 hours. If you are fortunate enough to eat three meals a day, you spend 12 out of every 24 hours in the absorptive state.

 

Some of the carbohydrates, lipids, and amino acids are broken down at once to provide energy for cellular operations. The remainder is stored, lessening the impact of future shortages. Insulin is the primary hormone of the absorptive state, although various other hormones stimulate amino acid uptake (growth hormone, or GH) and protein synthesis (GH, androgens, and estrogens).

 

 

The Liver
The liver regulates the levels of glucose and amino acids in the blood arriving in the hepatic portal vein before that blood reaches the inferior vena cava.

 

The liver uses some of the absorbed glucose to generate the ATP required to perform synthetic operations.

 

The liver does not control circulating levels of amino acids as precisely as it does glucose concentrations. Plasma amino acid levels normally range between 35 and 65 mg/dl, but they may become elevated after a protein–rich meal.

 

Liver cells can also synthesize many amino acids, and an amino acid present in abundance may be converted to another, less common type and released into the bloodstream.

Most of the lipids absorbed by the digestive tract do not reach the liver. Triglycerides, cholesterol, and large fatty acids reach the general venous circulation in chylomicrons that are transported in the thoracic duct. Most of these lipids are absorbed by other tissues.

 

Adipose Tissue
During the absorptive state, adipocytes remove fatty acids and glycerol from the bloodstream. Lipids continue to be removed from the blood for 4–6 hours after you have eaten a fatty meal.

 

Adipocytes also absorb amino acids as needed for protein synthesis. If, on a daily basis, you take in more nutrients during the absorptive state than you catabolize during the postabsorptive state, the fat deposits in your adipose tissue will enlarge. Most of the enlargement represents an increase in the size of individual adipocytes. An increase in the total number of adipocytes does not ordinarily occur, except in children before puberty and in extremely obese adults.

 

A useful definition of obesity is "20 percent above ideal weight," because that is the point at which serious health risks appear. On the basis of that criterion, 20–30 percent of men and 30–40 percent of women in the United States can be considered obese. Simply stated, obese individuals are taking in more food energy than they use.

 

Skeletal Muscle, Neural Tissue, and Other Peripheral Tissues
When blood glucose and amino acid concentrations are elevated, insulin is released from the pancreatic islets, and all tissues increase their rates of absorption and utilization. Glucose is catabolized for energy, and the amino acids are used to build proteins.

Glucose is normally retained in the body, because the kidneys prevent the loss of glucose molecules in urine.

 

When blood glucose levels are elevated, most cells ignore the circulating lipids, so the adipocytes have little competition. In resting skeletal muscles, a significant portion of the metabolic demand is met through the catabolism of fatty acids. Glucose molecules are used to build glycogen reserves, which may account for 0.5–1 percent of the weight of each muscle fiber.

 

The Postabsorptive State
The postabsorptive state is the period when nutrient absorption is not under way and your body must rely on internal energy reserves to continue meeting its energy demands. You spend roughly 12 hours each day in the postabsorptive state, although a person who is skipping meals can extend that time considerably. Metabolic activity in the postabsorptive state is focused on the mobilization of energy reserves and the maintenance of normal blood glucose levels.

 

 

Metabolic Reserves.
The distribution of the estimated metabolic reserves of a 70–kg individual

 

Due to its high energy content, the adipose tissue represents a disproportionate percentage of the total reserve in the form of triglycerides. Most of the available protein reserve is located in the contractile proteins of skeletal muscle. Carbohydrate reserves are relatively small and sufficient for only a few hours or, at most, overnight.

 

 

The Liver
As the absorptive state ends, your intestinal cells stop providing glucose to the portal circulation. At first, the peripheral tissues continue to remove glucose from the blood, and blood glucose levels begin to decline. The liver responds by reducing its synthetic activities. When plasma concentrations fall below 80 mg/dl, liver cells begin breaking down glycogen reserves and releasing glucose into the bloodstream. This glycogenolysis occurs in response to a rise in circulating levels of glucagon and epinephrine. The liver contains 75–100 g of glycogen that is readily available, a reserve that is adequate to maintain blood glucose levels for about four hours.

As glycogen reserves decline and plasma glucose levels fall to about 70 mg/dl, liver cells begin to make glucose in an attempt to stabilize blood glucose levels. The shift from glycogenolysis to gluconeogenesis occurs under stimulation by glucocorticoids , steroid hormones from the adrenal cortex.

Gluconeogenesis occurs as liver cells synthesize glucose molecules from smaller carbon fragments. In effect, any carbon fragment that can be converted to pyruvic acid or one of the three–carbon compounds involved in glycolysis in the cytoplasm can be used to synthesize glucose.

Utilization of Lipids In the postabsorptive state, your liver absorbs fatty acids and glycerol from the blood. The glycerol molecules are converted to glucose. Some of the acetyl–CoA molecules deliver their two–carbon acetyl fragments to the TCA cycle, during which they are broken down. The ATP generated can then be used to support gluconeogenesis.

In addition, some of the molecules of acetyl–CoA are converted to special compounds that can be utilized by peripheral tissues. These compounds, called ketone bodies , are organic acids that are also produced during the catabolism of Amino acids.

Utilization of Amino Acids Before an amino acid can be used for either gluconeogenesis or energy production by means of breakdown in the TCA cycle, the amino group must be removed. The structure of the remaining carbon chain determines its subsequent fate. After deamination, some amino acids can be converted to molecules of pyruvic acid or to one of the intermediary molecules of the TCA cycle. Other amino acids–including most of the essential amino acids–can be converted only to acetyl–CoA and must be either broken down further or converted to ketone bodies.  The liver is the most active site of amino acid breakdown. There, the ammonia generated by deamination is converted to urea.

 

During even a brief period of fasting, the increased production of ketone bodies results in ketosis, a high concentration of ketone bodies in body fluids. In ketosis, the concentration of ketone bodies is elevated in blood, a condition called ketonemia , and in urine, a condition called ketonuria. Ketonemia and ketonuria are clear indications that the catabolism of proteins and lipids is under way. Acetone, which diffuses out of the pulmonary capillaries and into the alveoli very readily, can be smelled on the individual's breath.

 

A ketone body is an acid that dissociates in solution, releasing a hydrogen ion. As a result, the appearance of ketone bodies in the bloodstream–ketonemia–is a threat to the plasma pH, which must be controlled by buffers. During prolonged starvation, ketone levels continue to rise. Eventually, buffering capacities are exceeded and a dangerous drop in pH occurs. This acidification of the blood is called ketoacidosis . In severe ketoacidosis, the circulating concentration of ketone bodies can reach 200 mg/dl, and the pH may fall below 7.05. A pH that low can disrupt tissue activities and cause coma, cardiac arrhythmias, and death

 

In diabetes mellitus , most peripheral tissues cannot use glucose, because they lack insulin. Under these circumstances, cells survive by catabolizing lipids and proteins. The result is the production of large numbers of ketone bodies. This condition leads to diabetic ketoacidosis , the most common and life–threatening form of ketoacidosis

 

Adipose Tissue
Adipose tissue contains a tremendous storehouse of energy in the form of triglycerides. Fat accounts for approximately 15 percent of the body weight of the average individual–enough to provide a 1–2 month reserve of ATP.

 

Typically, an individual's adipose tissue is distributed in the hypodermis (50 percent), in the greater omentum (10–15 percent), between muscles (5–8 percent), and around the kidneys (12 percent) and reproductive organs (15–20 percent).

As blood glucose levels decline, the rate of triglyceride synthesis falls. Under the stimulation of epinephrine, glucocorticoids, and growth hormone, adipocytes soon begin breaking down their lipid reserves, releasing fatty acids and glycerol into the bloodstream. This process, called fat mobilization , continues for the duration of the postabsorptive state. A normal individual retains about a two–months' supply of energy in the triglycerides of adipose tissue.

 

Skeletal Muscle

Skeletal muscle as a whole contains twice as much glycogen as the liver, but it is distributed throughout the muscular system. These glucose reserves are not directly available to other tissues, because the lack of a key enzyme makes skeletal muscle cells unable to release glucose into the bloodstream.

 

Even if all of the available glycogen reserves in your body were mobilized as glucose or as lactic acid, the energy provided would be only enough to get you through a good night's sleep. If the postabsorptive state continues for an unusually long period–long enough that lipid reserves are being depleted–muscle proteins will be broken down. The amino acids that are released diffuse into the blood for use by the liver in gluconeogenesis

 

Neural Tissue
Neurons are unusual in that they continue "business as usual" during the postabsorptive state. Neurons are dependent on a reliable supply of glucose, and changes in the activity of the liver, adipose tissue, skeletal muscle, and other peripheral tissues are intended to ensure that the supply of glucose to the nervous system continues unaffected, despite daily or even weekly changes in the availability of nutrients. Only after a prolonged period of starvation will neural tissue begin to metabolize ketone bodies and lactic acid molecules, as well as glucose

 

Diet and Nutrition
 The absorption of nutrients from food is called nutrition . A balanced diet contains all the ingredients necessary to maintain homeostasis, including adequate substrates for energy generation, essential amino acids and fatty acids, minerals, and vitamins. In addition, the diet must include enough water to replace losses in urine, feces, and evaporation. A balanced diet prevents malnutrition , an unhealthy state resulting from inadequate or excessive intake of one or more nutrients.

 

 

Food Groups and Food Pyramids
One method of avoiding malnutrition is to include members of each of the 6 basic food groups in the diet: (1) the milk, yogurt, and cheese group ; (2) the meat, poultry, fish, dry beans, eggs, and nuts group ; (3) the vegetable group ; (4) the fruit group ; (5) the bread, cereal, rice, and pasta group ; and (6) the fats, oils, and sweets group . Each group differs from the others in the typical balance of proteins, carbohydrates, and lipids it contains, as well as in the amount and identity of vitamins and minerals. The 6 groups are arranged in a food pyramid , which has the bread, cereal, rice, and pasta group at the bottom

 

 

What is important is that you obtain nutrients in sufficient quantity (adequate to meet your energy needs) and quality (including essential amino acids, fatty acids, vitamins, and minerals).

 

For example, consider the case of the essential amino acids. Your liver cannot synthesize any of these amino acids, and you must obtain them from your diet. Some members of the meat and dairy groups, such as beef, fish, poultry, eggs, and milk, provide all the essential amino acids in sufficient quantities. They are said to contain complete proteins . Many plants, while they also supply adequate amounts of protein, contain incomplete proteins , which are deficient in one or more of the essential amino acids. Vegetarians, who restrict themselves to the fruit and vegetable groups (with or without the bread group), must become adept at juggling the constituents of their meals to include a combination of ingredients that will meet all their amino acid requirements. Even with a proper balance of amino acids, vegetarians face a significant problem, because vitamin is obtained only from animal products or from fortified cereals or tofu.

 

Nitrogen Balance
A variety of important compounds in the body contain nitrogen atoms. These N compounds include:

Amino acids, which are part of the framework of all proteins and protein derivatives, such as glycoproteins and lipoproteins.

Purines and pyrimidines, the nitrogenous bases of RNA and DNA.

Creatine , important in energy storage in muscle tissue (as creatine phosphate).

Porphyrins , complex ring–shaped molecules that bind metal ions and are essential to the function of hemoglobin, myoglobin, and the cytochromes.

Despite the importance of nitrogen to these compounds, your body neither stores nitrogen nor maintains reserves of N compounds as it does carbohydrates (glycogen) and lipids (triglycerides).

 

You are in nitrogen balance if the amount of nitrogen you absorb from the diet balances the amount you lose in urine and feces.

 

The body contains only about a kilogram of nitrogen tied up in N compounds, and a decrease of one–third can be fatal. Even when energy reserves are mobilized, as during starvation, carbohydrates and lipid reserves are broken down first and N compounds are conserved.

Like N compounds, minerals and vitamins are essential components of the diet. Your body cannot synthesize minerals, and your cells can generate only a small quantity of a very few vitamins.

 

Minerals are inorganic ions released through the dissociation of electrolytes. Minerals are important for three reasons:

 

Ions such as Sodium and Chloride Determine the Osmotic Concentrations of Body Fluids. Potassium is important in maintaining the osmotic concentration of the cytoplasm inside body cells.

Ions in Various Combinations Play Major Roles in Important Physiological Processes.

Ions Are Essential Cofactors in a Variety of Enzymatic Reactions. For example, the calcium–dependent ATPase in skeletal muscle also requires the presence of magnesium ions, and another ATPase required for the conversion of glucose to pyruvic acid needs both potassium and magnesium ions.

 

 

Vitamins
Vitamins are assigned to either of two groups, according to their chemical structure and characteristics: (1) fat–soluble vitamins or (2) water–soluble vitamins .

Fat–Soluble Vitamins
Vitamins A, D, E, and K are the fat–soluble vitamins . These vitamins are absorbed primarily from your digestive tract along with the lipid contents of micelles. However, when exposed to sunlight, your skin can synthesize small amounts of vitamin D, and intestinal bacteria produce some vitamin K.

 

 

Because they dissolve in lipids, fat–soluble vitamins normally diffuse into cell membranes and other lipids in the body, including the lipid inclusions in the liver and adipose tissue. Your body therefore contains a significant reserve of these vitamins, and normal metabolic operations can continue for several months after dietary sources have been cut off. For this reason, symptoms of avitaminosis , or vitamin deficiency disease , rarely result from a dietary insufficiency of fat–soluble vitamins.

 

Too much of a vitamin can produce effects just as unpleasant as too little. Hypervitaminosis  occurs when the dietary intake exceeds the body's abilities to store, utilize, or excrete a particular vitamin. This condition most commonly involves one of the fat–soluble vitamins, because the excess is retained and stored in body lipids.

 

Vitamin A toxicity is the most common condition, afflicting some children whose parents are overanxious about proper nutrition and vitamins. A single enormous overdose can produce nausea, vomiting, headache, dizziness, lethargy, and even death. Chronic overdose can lead to hair loss, joint pain, hypertension, weight loss, and liver enlargement.

 

At least 19 cases of vitamin D toxicity were reported in the Boston area during 1992. Symptoms included fatigue, weight loss, and potentially severe damage to the kidneys and cardiovascular system. The problems resulted from drinking milk containing dangerous amounts of vitamin D. Due to problems at one dairy, some of the milk sold had over 230,000 units of vitamin D per quart instead of the usual 400 units per quart.

 

Water–Soluble Vitamins
Most of the water–soluble vitamins are components of coenzymes

 

 

Water–soluble vitamins are rapidly exchanged between the fluid compartments of the digestive tract and the circulating blood, and excessive amounts are readily excreted in urine.

 

For this reason, hypervitaminosis involving water–soluble vitamins is relatively uncommon except among individuals taking large doses of vitamin supplements. However, only vitamins and C are stored in significant quantities, so insufficient intake of other water–soluble vitamins can lead to initial symptoms of vitamin deficiency within a period of days to weeks.
The bacterial inhabitants of our intestines help prevent deficiency diseases by producing small amounts of five of the nine water–soluble vitamins, in addition to fat–soluble vitamin K. Your intestinal epithelium can easily absorb all the water–soluble vitamins except b-12.

 

Alcohol: A Risky Diversion

Alcoholism affects more than 10 million people in the United States alone. The lifetime risk of developing alcoholism for those who drink alcohol is estimated at 10 percent.

Alcoholism is probably society's most expensive health problem, with an annual estimated direct cost of more than $136 billion. Indirect costs, in terms of damage to automobiles, property, and innocent victims of accidents, are unknown.

An estimated 25–40 percent of U.S. hospital patients are undergoing treatment related to alcohol consumption. Approximately 200,000 deaths occur annually due to alcohol–related medical conditions. Some major clinical conditions are caused almost entirely by alcohol consumption. For example, alcohol is responsible for 60–90 percent of all liver disease in the United States.

Alcohol affects all physiological systems. Major clinical symptoms of alcoholism include (1) disorientation and confusion (nervous system); (2) ulcers, diarrhea, and cirrhosis (digestive system); (3) cardiac arrhythmias, cardiomyopathy, and anemia (cardiovascular system); (4) depressed sexual drive and testosterone levels (reproductive system); and (5) itching and angiomas (integumentary system).

The toll on newborn infants has risen steadily since the 1960s as the number of women drinkers has increased. Women consuming 1 ounce of alcohol per day during pregnancy have a higher rate of spontaneous abortion and produce children with lower birth weights than do women who consume no alcohol. Women who drink heavily may bear children with fetal alcohol syndrome (FAS) , a condition marked by characteristic facial abnormalities, a small head, slow growth, and mental retardation.

Alcohol abuse is considerably more widespread than alcoholism. Although the medical effects are less well documented, they are certainly significant

Eating Disorders

 

The most common conditions are anorexia nervosa , characterized by self–induced starvation, and bulimia , characterized by feeding binges followed by vomiting, the use of laxatives, or both. Adolescent females account for most cases of anorexia nervosa and bulimia; males account for only 5–10 percent. A common thread in the two conditions is an obsessive concern about food and body weight.

 

According to current estimates, the incidence of anorexia nervosa in the United States ranges from 0.4 to 1.5 per 100,000 population. The incidence among Caucasian women age 12–18 is estimated to be 1 percent. A typical person with this condition is an adolescent Caucasian woman whose weight is roughly 30 percent below normal levels. Although underweight, she is convinced that she is too fat, so she refuses to eat normal amounts of food.

 

Dry skin, peripheral edema, an abnormally low heart rate and blood pressure, a reduction in bone and muscle mass, and a cessation of menstrual cycles are relatively common symptoms. Some of the changes, especially in bone mass, can be permanent. Treatment is difficult, and only 50–60 percent of anorexics who regain normal weight stay there for five years or more. Death rates from severe anorexia nervosa range from 10 to 15 percent.

 

Bulimia is more common than anorexia nervosa. In this condition, the individual goes on an "eating binge" that may involve a meal that lasts an hour or two and may include 20,000 or more calories. The meal is followed by induced vomiting, commonly accompanied by the use of laxatives (drugs that promote the movement of the material through the digestive tract) and diuretics (drugs that promote fluid loss through urination).

 

The health risks of bulimia result from (1) cumulative damage to the stomach, esophagus, oral cavity, and teeth by repeated exposure to stomach acids; (2) electrolyte imbalances resulting from the loss of sodium and potassium ions in the gastric juices, diarrhea, and urine; (3) edema; and (4) cardiac arrhythmias.