Proteins are linear chains of amino acids connected by chemical bonds between the carboxyl group of each amino acid and the amine group of the one following. These bonds are called peptide bonds, and chains of only a few amino acids are referred to as polypeptides rather than proteins.
Proteins are all around us. Much of the body's dry weight is protein; even bones are about one-quarter protein. The animals we eat and the microbes that attack us are likewise largely protein. The leather, wool, and silk clothing that we wear are nearly pure protein. The insulin that keeps diabetics alive and the "clot-busting" enzymes that may save heart attack patients are also proteins. Proteins can even be found working at industrial sites—protein enzymes produce not only the high-fructose corn syrup that sweetens most soft drinks, but also fuel-grade ethanol (alcohol) and other gasoline additives.
Within our bodies and those of other living things, proteins serve many functions. They digest foods and turn them into energy; they move our bodies and move molecules about within our cells; they let some substances pass through cell membranes while keeping others out; they turn light into chemical energy, making both vision and photosynthesis possible; they allow cells to detect and react to hormones and toxins in their surroundings; and, as antibodies, they protect our bodies against foreign invaders. There are simply too many proteins—possibly more than 100,000—to even consider mentioning them all.
Proteins are made up of separate compounds called amino acids. It is these amino acids that our bodies actually need, not the entire protein molecule. Some amino acids are essential—they must be obtained from diet because they cannot be synthesized by humans in adequate amounts. There are nine essential amino acids. Others are nonessential, because they can be made in the body from precursors (components) of other amino acids. There are eleven nonessential amino acids.
Many proteins have components other than amino acids. For example, some may have sugar molecules chemically attached. Exactly which types of sugars are involved and where on the protein chain attachment occurs will vary with the specific protein. In a few cases, it may also vary among different people. The A, B, and O blood types, for example, differ in precisely which types of sugar are or are not added to a specific protein on the surface of red blood cells.
Other proteins may have fat-like (lipid) molecules chemically bonded to them. These sugar and lipid molecules are always added after synthesis of the protein's amino acid chain is complete. Such molecules can significantly affect the protein's properties.
Many other types of molecules may also be associated with proteins. Some proteins, for example, have specific metal ions associated with them. Others carry small molecules that are essential to their activity. Still others associate with nucleic acids in chromosomal or ribosomal structures.
Scientists have traditionally addressed protein structure at four levels: primary, secondary, tertiary, and quaternary. Primary structure is simply the linear sequence of amino acids in the peptide chain. It determines the protein's shape. Secondary and tertiary structure both refer to the three-dimensional shape into which a protein chain folds. The distinction is partly historical: secondary structure refers to certain highly regular arrangements of amino acids that scientists could detect as long ago as the 1950s, while tertiary structure refers to the complete three-dimensional shape. Tertiary structure determines the function of the protein. Determining a protein's tertiary structure can be difficult even today, although researchers have made major strides within the past decades.
The tertiary structure of many proteins shows a "string of beads" organization. The protein includes several compact regions known as domains, separated by short stretches in which the protein chain assumes an extended, essentially random configuration. Some scientists believe that domains were originally separate proteins that, over the course of evolution, have come together to perform their functions more efficiently.
Quaternary structure refers to the way in which protein chains—either identical or different—associate with each other. For example, a complete molecule of the oxygen-carrying protein hemoglobin includes four protein chains of two slightly different types. Simple laboratory tests usually allow scientists to determine how many chains make up a complete protein molecule.
PRIMARY PROTEIN STRUCTURE: PEPTIDE-CHAIN SYNTHESIS. Proteins are made (synthesized) in living things according to "directions" given by DNA and carried out by RNA and proteins. The synthesized protein's linear sequence of amino acids is ultimately determined by the linear sequence of DNA bases—or of base triplets known as codons—in the gene that codes for it. Each cell possesses elaborate machinery for producing proteins from these blueprints.
The first step is copying the DNA blueprint, essentially fixed within the cell nucleus, into a more mobile form. This form is messenger ribonucleic acid (mRNA), a single-stranded nucleic acid carrying essentially the same sequence of bases as the DNA gene. The mRNA is free to move into the main part of the cell, the cytoplasm, where protein synthesis takes place.
Besides mRNA, protein synthesis requires ribosomes and transfer ribonucleic acid (tRNA). Ribosomes are the actual "factories" where synthesis takes place, while tRNA molecules are the "trucks" that bring amino acids to the ribosome and ensure that they are incorporated at the right spot in the growing chain.
Ribosomes are extremely complex assemblages. They comprise almost 70 different proteins and at least three different types of RNA, all organized into two different-sized subunits. As protein synthesis begins, the previously separate subunits come together at the beginning of the mRNA chain; all three components are essential for the synthetic process.
Transfer RNA molecules are rather small, only about 80 nucleotides long. (Nucleotides are the fundamental building blocks of nucleic acids, as amino acids are of proteins.) Each type of amino acid has at least one corresponding type of tRNA (sometimes more). This correspondence is enforced by the enzymes that attach amino acids to tRNA molecules, which "recognize" both the amino acid and the tRNA type and do not act unless both are correct.
Transfer RNA molecules are not only trucks but translators. As the synthetic process adds one amino acid after another, they "read" the mRNA to determine which amino acid belongs next. They then bring the proper amino acid to the spot where synthesis is taking place, and the ribosome couples it to the growing chain. The tRNA is then released and the ribosome then moves along the mRNA to the next codon; that is, the next base triplet specifying an amino acid. The process repeats until the "stop" signal on the mRNA is reached, upon which the ribosome releases both the mRNA and the completed protein chain and its subunits separate to seek out other mRNAs.
SECONDARY STRUCTURE. The two major types of secondary structure are the alpha helix and the beta sheet, both discovered by Linus Pauling and R. B. Corey in 1951.
In an alpha helix, the backbone atoms of the peptide chain—the carboxyl carbon atom, the a-carbon atom (to which the side chain is attached), and the amino nitrogen atom—take the form of a three-dimensional spiral. The helix is held together by hydrogen bonds between each nitrogen atom and the oxygen atom of the carboxyl group belonging to the fourth amino acid up the chain.
Beta sheets feature several peptide chains lying next to each other in the same plane. The stabilizing hydrogen bonds are between nitrogen atoms on one chain and carboxyl-group oxygen atoms on the adjacent chain. Since each amino acid has its amino group hydrogen-bonded to the chain on one side and its carboxyl group to the chain on the other side, sheets can grow indefinitely.
TERTIARY STRUCTURE. Within seconds to minutes of their synthesis on ribosomes, proteins fold up into an essentially compact three-dimensional shape—their tertiary structure. Ordinary chemical forces fully determine both the steps in the folding pathway and the stability of the final shape. Some of these forces are hydrogen bonds between side chains of specific amino acids. Others involve electrical attraction between positively and negatively charged side chains. Perhaps most important, however, are what are called hydrophobic interactions—a scientific restatement of the observation that oil and water do not mix.
Some amino acid side chains are essentially oil-like (hydrophobic—literally, "water-fearing"). They accordingly stabilize tertiary structures that place them in the interior, largely surrounded by other oil-like side chains. Conversely, some side chains are charged or can form hydrogen bonds. These are hydrophilic, or "water-loving," side chains. Unless they form hydrogen or electrostatic
The forces that govern a protein's tertiary structure are simple. With thousands or even tens of thousands of atoms involved, however, the interactions can be extremely complex. Today's scientists are only beginning to discover ways to predict the shape a protein will assume and the folding process it will go through to reach that shape.
Digestion, metabolism, and elimination
Food in the human diet consists of proteins, carbohydrates, fats, vitamins, and minerals. The majority of minerals and vitamins pass through to the bloodstream without the need for further digestive changes, but other nutrient molecules must be broken down to simpler substances before they can be absorbed and used. Foods in the stomach are broken down by the action of the gastric juice containing hydrochloric acid and a protein-digesting enzyme called pepsin. Gastric juice is needed mainly for the digestion of protein by pepsin. If a hamburger and bun reach the stomach, there is no need for extra gastric juice for the bun (carbohydrate), but the hamburger (protein) will require a much greater supply of gastric juice. The gastric juice already present will begin the breakdown of the large protein molecules of the hamburger into smaller molecules: polypeptides and peptides.
From the time a protein-containing food is eaten, to its breakdown and subsequent use or excretion, many complicated processes and steps take place in the body. These processes are part of metabolism, in which a series of metabolic pathways are involved in the breakdown of the foods. Proteins are initially degraded into constituent amino acids, which may be converted to compounds called pyruvic acid or acetyl-CoA before being passed into the metabolic pathway known as the Krebs cycle; or they may enter the Krebs cycle directly after being converted into one of the metabolites of this metabolic pathway.
Proteins contain substantial amounts of nitrogen. When dietary protein is broken down into amino acids, nitrogen is produced and is eliminated in the urine in the form of urea, and in smaller amounts as uric acid, ammonia, and creatinine. Unabsorbed protein is excreted in the feces, but only about 10 grams per day because protein is used very efficiently in the body. Amino acids may be recycled many times for different functions. There are minute losses of protein as skin, or in menstrual blood, semen, and hair.
After water, protein makes up the greatest percentage of human body weight. This key nutrient provides the building blocks children and adults need for growing, maintaining, and repairing worn-out cells. Without protein, human bodies could not regulate fluids and immune systems would shut down. In fact, if not for protein there would be no hormones or enzymes—the protein compounds that take part in every single physical function. The role of protein in the diet is mainly as a source of amino acids, some of which are essential because they cannot be produced in the body. Others are referred to as nonessential because they can be made in the body from simple precursors. Amino acids are central to every human bodily function with every chemical reaction that occurs. Some of the uses of amino acids are:
- Synthesis of substances called purines and pyrimidines, important for deoxyribonucleic acid (DNA).
- Producing creatine in skeletal muscle; creatine is needed for subsequent production of creatinine.
- Building and maintaining muscle and tissues.
- Maintaining proper cellular function.
- Controlling chemical reactions through enzymes.
There are also circulating proteins in the plasma of the blood that vary depending on the levels in the diet. Some examples of plasma proteins with important functions in the body are: serum albumin, retinal binding protein, fibrinogen, etc. If the protein intake is low, these proteins will be reduced in the blood and therefore their functions in the body may be affected.
Approximately 300 grams of protein is produced per day in the body with a dietary intake of about 100 grams. Some of the protein needed is acquired from endogenous sources (in the body from protein breakdown) and is released into the intestinal lumen; it is estimated at about 70 grams per day.
Role in human health
The human body, minus water, is mostly composed of amino acids. Almost all of the hormones are amino acids. Regulation of protein metabolism is necessary to maintain proper bodily function; therefore, it is important to eat protein-rich foods. Protein is also important for building body tissue and synthesizing enzymes. Twenty amino acids are used for protein synthesis. Animals and plants are quick and available sources of what are termed "essential" amino acids; they are called essential because the body cannot internally build them. Normal growth and health are dependent upon these essential amino acids. These essential amino acids are histidine, tryptophan,
On a per kilogram basis, protein requirements in humans are highest in infancy and gradually decline throughout one's life, except in such circumstances as pregnancy, lactation, and illness. The Recommended Daily Allowance (RDA) suggests protein requirements based on age incrementally. The amount of protein needed also depends on body weight, but it is not a linear relationship. A person who weighs 400 lbs (181.43 kg). does not need four times as much protein as a person weighing 100 lbs (45.35 kg). From birth to three months, protein needs are at their highest (2.2 grams per kilogram of body weight). The requirement for adult males and females is 0.8 g/kg. This amount is equal to about 63 grams of dietary protein for a male aged 25-50 years who weighs 174 lbs. (79 kg), and 50 grams for a female aged 25-50 years who weighs 139 lbs. (63 kg). The average Western diet contains ample amounts of protein. In fact, most people in industrialized countries eat more protein than they need. In the United States, true protein deficiency is rare except when excess protein is lost and protein requirements are increased, as in cases of:
- wasting and/or cachexia associated with cancer (Approximately half of all cancer patients experience cachexia, a wasting syndrome that induces metabolic changes leading to a loss of muscle and fat.)
- chronic renal failure, when the patient is undergoing hemodialysis or peritoneal dialysis
Protein requirements may also be increased in training athletes because of greater muscle mass during training season.
In general, consequences of inadequate protein intake may include a faster loss of muscle mass from the body; higher risks of infection; and reduced protein reserves for use during periods of trauma or infection. In addition, protein breakdown is rapid when a person is fasting or bedridden.
Dietary sources of protein
Meat, milk, eggs, poultry, and seafood are considered high-quality, "complete" proteins because they have all the essential amino adds (protein's building blocks) in just the right proportion. Those sources are considered more complete than vegetable protein, such as beans, peas, and grains, also considered a good—even if not complete—source of amino acids. Except for soy, plant sources—nuts, beans, seeds, and grains—are deficient in one or more of the essential amino acids. But plant foods contain other vital nutrients (such as phytochemicals and fiber) not found in animal foods. Dietitians recommend that a healthy diet should consist of foods from a variety of sources and should include 10–20% of daily calories from protein (poultry, fish, dairy, soy protein, nuts, legumes, eggs, peanut butter, and vegetable sources).
The food pyramid, developed by nutritionists, provides a visual guide to healthy eating. At its base are those foods that should be eaten numerous times each day, while at its apex are those foods that should be used sparingly. The pyramid suggests a range of servings in each group so that the number of servings can be adjusted to suit each individual's caloric requirements. The daily recommendations (from bottom to top) of the food pyramid include:
- Bread, cereal, rice, and pasta: 6–11 servings.
- Vegetables: 3–5 servings.
- Fruits: 2–4 servings.
- Milk, yogurt, and cheese: 2–3 servings.
- Meat, poultry, fish, dried beans, eggs, and nuts: 2–3 servings.
- Fats, oils, and sweets: use sparingly.
High-protein diets are designed to provide about 1.5 g of protein for each kilogram of a person's body weight. Complex proteins, such as milk and meats, should make up one-half to two-thirds of the daily protein requirement. High-protein diets are recommended for people who:
- Have an increased need for protein due to protein-calorie malnutrition; severe stress; or such conditions as AIDS, cancer, or burns with high metabolic rates that lead to the loss of large amounts of protein.
- Have malabsorption syndromes, celiac disease, or other disorders characterized by poor food absorption.
A low-protein diet excludes dairy products and meats, and requires that about three-fourths of the daily allowance of protein come from high-value protein sources. Supplements may be prescribed to prevent amino-acid deficiencies. Low-protein diets are used in treatment of conditions such as liver cirrhosis and kidney disease (excluding chronic renal failure patients who have increased protein needs because of losses that occur during dialysis).
Common diseases and disorders
The metabolic pathways in the body for protein metabolism and energy metabolism are interrelated. Certain metabolic conditions distort this relationship, namely diabetes, kidney failure, fever, cancer, and liver cirrhosis.
Inborn errors of metabolism (also called human hereditary biochemical disorders) have genetic origins; these errors interfere with the synthesis of proteins, carbohydrates, fats, enzymes, and many other substances in
Celiac disease, also known as nontropical sprue, gluten enteropathy, or celiac sprue, is an inherited disorder resulting in malabsorption because of an allergic reaction after consumption of a protein called gluten. This intolerance causes patients with celiac disease to suffer weight loss, diarrhea, malnutrition, and bloating. By eliminating foods containing gluten from the diet, further damage to the intestines can be prevented, symptoms are relieved, and malabsorption of nutrients is corrected. Gluten is found in wheat, rye, barley, and oats. Registered dietitians and physicians can assist the patient with the diet modifications needed for each disease.
Other conditions that may occur due to protein metabolism or absorption abnormalities include:
- muscle wasting and atrophy, which may occur when there is decreased protein absorption and metabolism due to causes such as malabsorption syndrome
- edema (fluid retention in the body's tissues) due to decreased protein absorption
- malnutrition and weight loss due to decreased fat, carbohydrate, and protein absorption
Protein-calorie malnutrition (or protein-energy malnutrition) is a condition associated most closely with weight loss, starvation, or illness and is common in cancer patients. It occurs when a lack of protein and calories are consumed to sustain body composition. When inadequate calories are consumed, the body's functionality declines, which may lead to illness and perhaps death. Exhaustion, weakness, decreased resistance to infection, and a progressive wasting of body muscle and fat stores occur.
Certain conditions may require protein restrictions; for example, acute liver or kidney failure, and uremia (increased urea in the blood).
Powder and tablet forms of amino acids have become popular as health supplements. But their prolonged excessive use can upset the natural amino acid balance and lead to kidney, liver, and nervous system damage. Do not take these supplements without first consulting a registered dietitian or physician.
Alpha helix—A type of secondary structure in which a single peptide chain arranges itself in a three-dimensional spiral.
Beta sheet—A type of secondary structure in which several peptide chains arrange themselves alongside each other.
Cachexia—A condition in which the body weight "wastes" away, characterized by a constant loss of weight, muscle, and fat.
Creatine—A substance found in skeletal muscles; it is produced by other amino acids.
Domain—A relatively compact region of a protein, separated from other domains by short stretches in which the protein chain is more or less extended; different domains often carry out distinct parts of the protein's overall function.
Enzymes—Enzymes are protein catalysts that increase the speed of chemical reactions in the cell without themselves being changed.
Hormones—Hormones are messengers that travel to tissues or organs, where they may stimulate or inhibit specific metabolic pathways.
Messenger ribonucleic acid (mRNA)—A molecule of RNA that carries the genetic information for producing one or more proteins; mRNA is produced by copying one strand of DNA, but is able to move from the nucleus to the cytoplasm (where protein synthesis takes place).
Peptide bond—A chemical bond between the carboxyl group of one amino acid and the amino nitrogen atom of another.
Phenylketonuria (PKU)—A rare hereditary condition in which phenylalanine (an amino acid) is not properly metabolized. PKU may cause severe mental retardation.
Polypeptide—A group of amino acids joined by peptide bonds; proteins are large polypeptides, but no agreement exists regarding how large they must be to justify the name.
Primary structure—The linear sequence of amino acids making up a protein.
Quaternary structure—The number and type of protein chains normally associated with each other in the body.
Protein-calorie malnutrition—A lack of protein and calories are consumed to sustain the body composition, resulting in weight loss and muscle wasting.
Ribosome—A very large assemblage of RNA and protein that, using instructions from mRNA, synthesizes new protein molecules.
Secondary structure—Certain highly regular three-dimensional arrangements of amino acids within a protein.
Tertiary structure—A protein molecule's overall three-dimensional shape.
Transfer ribonucleic acid (tRNA)—A small RNA molecule, specific for a single amino acid, that transports that amino acid to the proper spot on the ribosome for assembly into the growing protein chain.
Wasting—When inadequate calories are consumed, it can lead to "wasting" or depletion of body mass. Wasting results in weight loss in such tissues as skeletal muscle and adipose tissue (fat).
Institute of Medicine. Dietary Reference Intakes: Applications in Dietary Assessment. Washington, D.C.: National Academy Press, 2001.
Lobley, Gerald E., et al., eds. Protein Metabolism and Nutrition. West Lafayette, IN: Purdue University Press, 1999.
Mahan, L. Kathleen, and Sylvia Escott-Stump., eds. Krause's Food, Nutrition, & Diet Therapy. London, UK: W. B. Saunders Co., 2000.
Rodwell-Williams, Sue. Essentials of Nutrition and Diet Therapy (With CD-ROM for Windows and Macintosh). London, UK: Mosby-Year Book, 1999.
Salway, J.G. Metabolism at a Glance, 2nded., Oxford, UK: Blackwell Science Inc., 1999.
Welle, Stephen. Human Protein Metabolism. New York: Springer Verlag, 1999.
White, John S., and Dorothy C. White, eds. Proteins, Peptides, & Amino Acids Source Book. Totowa, NJ: Humana Press Inc., 2001.
Omran M. L., and J. E. Morley. "Assessment of protein energy malnutrition in older persons, part I: History, examination, body composition, and screening tools." Nutrition 16, no. 1 (January 2000): 50-63.
American Dietetic Association. 216 W. Jackson Blvd., Chicago, IL 60606-6995. (312) 899-0040. <http://www.eatright.org/>.
Food and Nutrition Information Center Agricultural Research Service, USDA. National Agricultural Library, Room 304, 10301 Baltimore Avenue, Beltsville, MD 20705-2351. (301) 504-5719. Fax: (301) 504-6409. <http://www.nal.usda.gov/fnic/>. firstname.lastname@example.org.
Crystal Heather Kaczkowski, MSc.