PROTEIN

highly complex substance that is present in all living organisms. Proteins are of great nutritional value and are directly involved in the chemical processes essential for life. The importance of proteins was recognized by the chemists in the early 19th century who coined the name for these substances from the Greek proteios, meaning holding first place. Proteins are species-specific; that is, the proteins of one species differ from those of another species. They are also organ-specific; for instance, within a single organism, muscle proteins differ from those of the brain and liver. A protein molecule is very large compared to molecules of sugar or salt and consists of many amino acids joined together to form long chains, much as beads are arranged on a string. There are about 20 different amino acids that occur naturally in proteins. Proteins of similar function have similar amino acid composition and sequence. Although it is not yet possible to explain all of the functions of a protein from its amino acid sequence, established correlations between structure and function can be attributed to the properties of the amino acids that compose proteins. Plants can synthesize all of the amino acids; animals cannot, even though all of them are essential for life. Plants can grow in a medium containing inorganic nutrients that provide nitrogen, potassium, and other substances essential for growth. They utilize the carbon dioxide in the air during the process of photosynthesis to form organic compounds such as carbohydrates. Animals, however, must obtain organic nutrients from outside sources. Because the protein content of most plants is low, very large amounts of plant material are required by animals, such as ruminants (e.g., cows), that eat only plant material to meet their amino acid requirements. Nonruminant animals, including man, obtain proteins principally from animals and their productse.g., meat, milk, and eggs. The seeds of legumes are increasingly being used to prepare inexpensive protein-rich food (see nutrition: Human nutrition and diet). The protein content of animal organs is usually much higher than that of the blood plasma. Muscles, for example, contain about 30 percent protein, the liver 20 to 30 percent, and red blood cells 30 percent. Higher percentages of protein are found in hair, bones, and other organs and tissues with a low water content. The quantity of free amino acids and peptides in animals is much smaller than the amount of protein. Evidently, protein molecules are produced in cells by the stepwise alignment of amino acids and are released into the body fluids only after synthesis is complete. The high protein content of some organs does not mean that the importance of proteins is related to their amount in an organism or tissue; on the contrary, some of the most important proteins, such as enzymes and hormones, occur in extremely small amounts. The importance of proteins is related principally to their function. All enzymes identified thus far are proteins. Enzymes, which are the catalysts of all metabolic reactions, enable an organism to build up the chemical substances necessary for lifeproteins, nucleic acids, carbohydrates, and lipidsto convert them into other substances, and to degrade them. Life without enzymes is not possible. There are several protein hormones with important regulatory functions. In all vertebrates, the respiratory protein hemoglobin acts as oxygen carrier in the blood, transporting oxygen from the lung to body organs and tissues. A large group of structural proteins maintains and protects the structure of the animal body. complex molecule composed of amino acids and necessary for the chemical processes that occur in living organisms. Proteins are basic constituents in all living organisms. Their central role in biological structures and functioning was recognized by chemists in the early 19th century when they coined the name for these substances from the Greek word proteios, meaning holding first place. Proteins constitute about 80 percent of the dry weight of muscle, 70 percent of that of skin, and 90 percent of that of blood. The interior substance of plant cells is also composed partly of proteins. The importance of proteins is related more to their function than to their amount in an organism or tissue. All known enzymes, for example, are proteins and may occur in very minute amounts; nevertheless, these substances catalyze all metabolic reactions, enabling organisms to build up the chemical substancesother proteins, nucleic acids, carbohydrates, and lipidsthat are necessary for life. Proteins are sometimes referred to as macromolecular polypeptides because they are very large molecules and because the amino acids of which they are composed are joined by peptide bonds. (A peptide bond is a link between the amino group of one amino acid and the carboxyl group of the next amino acid in the protein chain.) Although amino acids may have other formulas, those in protein invariably have the general formula RCH(NH2)COOH, where C is carbon, H is hydrogen, N is nitrogen, O is oxygen, and R is a group, varying in composition and structure, called a side chain. Amino acids are joined together to form long chains; most of the common proteins contain more than 100 amino acids. The vast majority of the proteins found in living organisms are composed of only 20 different kinds of amino acids, repeated many times and strung together in a particular order. Each type of protein has its own unique sequence of amino acids; this sequence, known as its primary structure, actually determines the shape and function of the protein. Interactions among the amino acids cause the protein chain to assume a characteristic secondary structure and, under some circumstances, a tertiary structure. The secondary structure is a function of the angles formed by the peptide bonds that link together the amino acids. These bond angles are held in position by the development of hydrogen bonds between the nitrogen-bound hydrogen atom of one amino acid unit and the oxygen atom of another. Commonly, these hydrogen bonds cause the chain to assume a helical secondary structurei.e., the backbone of the chain resembles a rope spirally wound along an imaginary tube. The tertiary structure refers to the looping and folding of the protein chain back upon itself. Such a structure characterizes the globular proteins (i.e., those with a more or less spherical shape). Tertiary structure is determined largely by the side chains of the amino acids. Some side chains are so large that they disrupt the regular helical secondary structure of the chain, causing it to have kinks and bends. Furthermore, side chains that carry opposite electrical charges attract one another and form ionic bonds; those with like electrical charges repel one another. Hydrophobic side chainsi.e., those that are insoluble in watercluster together at the centre of the folded protein, avoiding exposure to the aqueous environment. Hydrophilic side chains, which readily form hydrogen bonds with water molecules, are left on the outside of the protein structure. Some proteins, such as hemoglobin, are composed of more than one protein subunit (polypeptide chain). The spatial conformation of these chains is known as the quaternary structure. Quaternary structure is maintained by the same kinds of forces that determine tertiary structure. Proteins may be classified according to several methods. For example, they are sometimes classified as either simple or conjugated. Simple proteins consist only of amino acids. Conjugated proteins contain not only amino acids but also nonamino acid prosthetic groups. A prosthetic group may be a carbohydrate, lipid, nucleic acid, metal, pigment, or some other nonprotein molecule or ion. Many of these substances are vitamins or metals (trace elements) needed in small amounts in the diet. Hemoglobin is a well-known conjugated protein. A hemoglobin molecule contains four prosthetic groups, each consisting of the metal iron and the pigment porphyrin. These prosthetic groups enable hemoglobin to carry oxygen through the bloodstream. Proteins are also classified according to their function. Under this scheme, they can be divided into two main categories: structural proteins and biologically active proteins. A drawback to this system is that some proteins serve both as structural elements and as biologically active compounds. Most structural proteins are fibrousi.e., they are composed of elongated, threadlike chains. Major structural proteins in animals include collagen, which is the protein of bones, tendons, ligaments, and skin, and keratin, the protein of hair, nails, hoofs, and feathers. Biologically active proteins are mostly globular, their functional activity being directly related to their complex three-dimensional shape. Major kinds of biologically active proteins include enzymes, which catalyze chemical reactions in living systems; protein hormones, which serve as chemical messengers between different parts of the body; transport proteins, which carry substances from one part of the body to another; and immunoglobulins (or antibodies), which protect the body from microorganisms and other foreign substances. The sequence of amino acids in all proteins is genetically determined by the sequence of nucleotides in cellular DNA. When a particular protein is needed, the DNA code for that protein is transcribed into a sequence of complementary nucleotides along a segment of RNA. This RNA segment then serves as a template for subsequent protein synthesis. Each group of three nucleotides specifies a particular amino acid; the amino acids are assembled into the sequence coded by the RNA. Additional reading Comprehensive works are Henry R. Mahler and Eugene H. Cordes, Basic Biological Chemistry (1968); Abraham White et al., Principles of Biochemistry, 6th ed. (1978); Albert L. Lehninger, David L. Nelson, and Michael L. Cox, Principles of Biochemistry, 2nd ed. (1993); Thomas Briggs and Albert M. Chandler (eds.), Biochemistry, 2nd ed. (1992); John W. Hill, Dorothy M. Feigl, and Stuart J. Baum, Chemistry and Life, 4th ed. (1993); Lubert Stryer, Biochemistry, 3rd ed. (1988); Donald Voet and Judith G. Voet, Biochemistry (1990); Geoffrey Zubay, Biochemistry, 3rd ed. (1993); and Laurence A. Moran et al., Biochemistry, 2nd ed. (1994). David J. Holme and Hazel Peck, Analytical Biochemistry, 2nd ed. (1993), covers newer methods of analysis. The Editors of the Encyclopdia BritannicaWorks specifically on proteins include Hans Neurath and Robert L. Hill (eds.), The Proteins, 3rd ed. (1975 ), a comprehensive discussion of the structure, function, and biology of proteins; Margaret O. Dayhoff (ed.), Atlas of Protein Sequence and Structure (196578), describing three-dimensional protein structures known up to that time, now replaced by computer databases; Richard E. Dickerson and Irving Geis, Hemoglobin: Structure, Function, Evolution, and Pathology (1983); Carl Branden and John Tooze, Introduction to Protein Science (1991), a comprehensive survey of the classes of protein three-dimensional structures described to date; Murray P. Deutscher (ed.), Guide to Protein Purification (1990), a critical description of the principles and practice of the numerous methods used in preparing pure proteins; Colin T. Mant and Robert S. Hodges (eds.), High-Performance Liquid Chromatography of Peptides and Proteins: Separation, Analysis, and Conformation (1991); William S. Hancock (ed.), CRC Handbook of HPLC for the Separation of Amino Acids, Peptides, and Proteins, 2 vol. (1984); Elizabeth M. Slayter, Optical Methods in Biology (1970); Stanley Blackburn, Amino Acid Determination, 2nd ed., rev. and expanded (1978), a manual of method; and Stephen G. Waley, Mechanisms of Organic and Enzymic Reactions (1962), a short text emphasizing enzymatic mechanisms. Supplementary material includes Advances in Protein Chemistry (annual); Annual Review of Biochemistry; Cambridge Scientific Biochemistry Abstracts, part 3, Amino-Acids, Peptides, and Proteins (monthly); A. Niederwieser and G. Pataki (eds.), New Techniques in Amino Acid, Peptide and Protein Analysis (1971); Chemistry and Biochemistry of Amino Acids, Peptides, and Proteins (irregular); Enzyme Nomenclature 1992 (1992); Alan G. Walton, Polypeptides and Protein Structure (1981); and J.B.C. Findlay and M.J. Geisow (eds.), Protein Sequencing: A Practical Approach (1989). Felix Haurowitz The Editors of the Encyclopdia Britannica Classification of proteins Classification by solubility After two German chemists, Emil Fischer and Franz Hofmeister, independently stated in 1902 that proteins are essentially polypeptides consisting of many amino acids, an attempt was made to classify proteins according to their chemical and physical properties, because the biological function of proteins had not yet been established. (The protein character of enzymes was not proved until the 1920s.) Proteins were classified primarily according to their solubility in a number of solvents. This classification is no longer satisfactory, however, because proteins of quite different structure and function sometimes have similar solubilities; conversely, proteins of the same function and similar structure sometimes have different solubilities. The terms associated with the old classification, however, are still widely used. They are defined below. Albumins are proteins that are soluble in water and in water half-saturated with ammonium sulfate. On the other hand, globulins are salted out (i.e., precipitated) by half-saturation with ammonium sulfate. Globulins that are soluble in salt-free water are called pseudoglobulins; those insoluble in salt-free water are euglobulins. Both prolamins and glutelins, which are plant proteins, are insoluble in water; the prolamins dissolve in 50 to 80 percent ethanol, the glutelins in acidified or alkaline solution. The term protamine is used for a number of proteins in fish sperm that consist of approximately 80 percent arginine and therefore are strongly alkaline. Histones, which are less alkaline, apparently occur only in cell nuclei, where they are bound to nucleic acids. The term scleroproteins has been used for the insoluble proteins of animal organs. They include keratin, the insoluble protein of certain epithelial tissues such as the skin or hair, and collagen, the protein of the connective tissue. A large group of proteins has been called conjugated proteins, because they are complex molecules of protein consisting of protein and nonprotein moieties. The nonprotein portion is called the prosthetic group. Conjugated proteins can be subdivided into mucoproteins, which, in addition to protein, contain carbohydrate; lipoproteins, which contain lipids; phosphoproteins, which are rich in phosphate; chromoproteins, which contain pigments such as iron-porphyrins, carotenoids, bile pigments, and melanin; and finally, nucleoproteins, which contain nucleic acid. The weakness of the above classification lies in the fact that many, if not all, globulins contain small amounts of carbohydrate; thus there is no sharp borderline between globulins and mucoproteins. Moreover, the phosphoproteins do not have a prosthetic group that can be isolated; they are merely proteins in which some of the hydroxyl groups of serine are phosphorylated (i.e., contain phosphate). Finally, the globulins include proteins with quite different rolesenzymes, antibodies, fibrous proteins, and contractile proteins. Classification by biological functions In view of the unsatisfactory state of the old classification, it is preferable to classify the proteins according to their biological function. Such a classification is far from ideal, however, because one protein can have more than one function. The contractile protein myosin, for example, also acts as an ATPase (adenosine triphosphatase), an enzyme that hydrolyzes adenosine triphosphate (removes a phosphate group from ATP by introducing a water molecule). Another problem with functional classification is that the definite function of a protein frequently is not known. A protein cannot be called an enzyme as long as its substrate (the specific compound upon which it acts) is not known. It cannot even be tested for its enzymatic action when its substrate is not known.