Biochemistry - as science; Structure, properties and biological functions of proteins. Methods of secretion and purification. Peptides. Complex proteins, their biological role.

Proteins are the most abundant substances in most cells - from 10% to 20% of the cell’s mass. More than % of dry weight of muscles, lungs, kidneys, spleen; 57 % of dry weight of liver, 45 % of dry weight of brain are proteins. The lowest proteins constituting in bones and teeth (20 and 18 % responding). Contents of chemical elements in proteins: carbon is %, oxygen is %, nitrogen is %, hydrogen is 6-7 %, sulfur is %. Some proteins contain phosphorus iron, zinc, copper and other elements - (0.2-2%).

AMINO ACIDS An amino acid is an organic compound that contains both an amino (–NН 3 ) group and a carboxyl (-СООН) group. The amino acids found in proteins are always α-amino acids.

Reaction of amino acids Reaction with alcohols – esters formation: Reaction with ammonia – amides formation: Decarboxylation: Salts are formed:

Deamination oxidation deamination: hydrolitic deamination: intramolecular deamination: redaction deamination:

Classification of amino acids Nonpolar amino acids contain one amino group, one carboxyl group, and a nonpolar side chain. Polar neutral amino acids contain one amino group, one carboxyl group, and а side chain that is polar but neutral. Polar acidic amino acids contain one amino group and two carboxyl groups, the second carboxyl group being part of the side chain. There are two polar acidic amino acids: aspartic acid and glutamic acid. Polar basic amino acids contain two amino groups and one carboxyl group, the second amino group being part of the side chain. There are three polar basic amino acids: lysine, arginine, and histidine.

Essential and non-essential amino acids All of the 20 amino acids are necessary constituents of human protein. Adequate amounts of 11 of the 20 amino acids can be synthesized from carbohydrates and lipids in the body if а source of nitrogen is also available. Because the human body is incapable of producing 9 of these 20 acids, these 9 amino acids, called essential amino acids, must be obtained from food. The human body can synthesize small amounts of some of the essential amino acids, but not enough to meet its needs, especially in the case of growing children. The 9 essential amino acids for adults are histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. (In addition, arginine is essential for children).

Peptide formation Two amino acids can react in а similar way - the carboxyl group of one amino acid reacts with the amino group of the other amino acid. The products are а molecule of water and а molecule containing the two amino acids linked by an amide bond.

Peptides Short to medium-sized chains of amino acids are known as peptides. А peptide is а sequence of amino acids, of up to 50 units, in which the amino acids are joined together through amide (peptide) bonds. А compound containing two amino acids joined by а peptide bond is specifically called а dipeptide; three amino acids in а chain constitute а tripeptide; and so on. The name oligopeptide is loosely used to refer to peptides with 10 to 20 amino acid residues and polypeptide to larger peptides.

Proteins Proteins are polypeptides that contain more than 50 amino acid units. The dividing line between а polypeptide and а protein is arbitrary. The important point is that proteins are polymers containing а large number of amino acid units linked by peptide bonds. Polypeptides are shorter chains of amino acids. Some proteins have molecular masses in the millions. Some proteins also contain more than one polypeptide chain.

Function of proteins Catalysis. Enzymes, the proteins that direct and accelerate thousands of biochemical reactions Structure. Some proteins function as structural materials that provide protection and support. Movement. Proteins are involved in all types of cell movement. For example, actin, tubulin, and а variety of other proteins comprise the cytoskeleton. Defense. А wide variety of proteins have а protective role. Examples found in vertebrates include keratin, the protein found in skin cells that aids in protecting the organism against mechanical and chemical injury. The blood- clotting proteins fibrinogen and thrombin prevent blood loss when blood vessels are damaged. The immuno-globulins (or antibodies) are produced by lymphocytes in response to the invasion of foreign organisms such as bacteria. Regulation. The binding of а hormone molecule to its target cell results in specific changes in cellular function. Examples of peptide hormones include insulin and glucagon, which regulate blood glucose levels. Growth hormone stimulates cell growth and division. Transport. Many proteins function as carriers of molecules or ions across membranes or between cells. Examples of membrane proteins include the Na + - К + ATPase and the glucose transporter. Other transport proteins include hemoglobin, which carries O 2 to the tissues from the lungs, and the lipoproteins, which transport lipids from the liver and intestines to other organs

Primary structure of а protein The primary structure of а protein is the sequence of amino acids present in its peptide chain or chains. The end with the free H 3 N + group is called the N-terminal end, and the end with the free СОО - group is called the С- terminal end.

Primary structure

Secondary structure of а protein The secondary structure of а protein is the arrangement in space of the atoms in the backbone of the protein. Three major types of protein secondary structure are known; the alpha helix, the beta pleated sheet, and the triple helix. The major force responsible for all three types of secondary structure is hydrogen bonding between а carbonyl oxygen atom of а peptide linkage and the hydrogen atom of an amino group (-NH) of another peptide linkage farther along the backbone.

Secondary structure

Alpha Helix The Alpha Helix The alpha helix (α-helix) structure resembles а coiled helical spring, with the coil configuration maintained by hydrogen bonds between N – Н and С= О groups of every fourth amino acid

Beta pleated sheet The beta pleated sheet (β-pleated sheet) secondary structure involves amino acid chains that are almost completely extended.

Tertiary structure The tertiary structure of а protein is the overall three-dimensional shape that results from the attractive forces between amino acid side chains (R groups) that are widely separated from each other within the chain. There are four types of bonding interactions between "side chains" including: hydrogen bonding, salt bridges, disulfide bonds, and non-polar hydrophobic interactions.

Tertiary structure

hydrogen bonds; hydrophobic attractions; Interactions responsible for tertiary structure covalent disulfide bonds; electrostatic attractions (salt bridges);

Electrostatic attractions (salt bridges), Hydrogen bonds,

Quaternary structure Quaternary structure is the highest level of protein organization. It is found only in proteins that have structures involving two or more polypeptide chains that are independent of each other — that is, are not covalently bonded to each other. These multichain proteins are often called oligomeric proteins. The quaternary structure of а protein involves the associations among the separate chains in an oligomeric protein.

Hemoglobin

Globular and fibrous proteins On the basis of structural shape, proteins can be classified into two major types: fibrous proteins and globular proteins. А fibrous protein is а protein that has а long, thin, fibrous shape. Such proteins are made up of long rod-shaped or string- like molecules that can intertwine with one another and form strong fibers. They are water-insoluble and generally have structural functions within the human body. А globular protein is а protein whose overall shape is roughly spherical or globular. Globular proteins either dissolve in water or form stable suspensions in water, which allows them to travel through the blood and other body fluids to sites where their activity is needed.

Simple and Conjugated Proteins Proteins are classified as either simple proteins and conjugated proteins. А simple protein is made up entirely of amino acid residues. А complex protein has other chemical components in addition to amino acids. These additional components, which may be organic or inorganic, are called prosthetic groups.

Glycoproteins. Glycoproteins are proteins that contain carbohydrate. Proteins destined for an extracellular location are characteristically glycoproteins. For example, fibronectin and proteoglycans are important components of the extracellular matrix that surrounds the cells of most tissues in animals. Immunoglobulin G molecules are the principal antibody species found circulating free in the blood plasma. Many membrane proteins are glycosylated on their extracellular segments. Lipoproteins. Blood plasma lipoproteins are prominent examples of the class of proteins conjugated with lipid. The plasma lipoproteins function primarily in the transport of lipids to sites of active membrane synthesis. Serum levels of low density lipoproteins (LDLs) are often used as a clinical index of susceptibility to vascular disease. Nucleoproteins. Nucleoprotein conjugates have many roles in the storage and transmission of genetic information. Ribosomes are the sites of protein synthesis. Virus particles and even chromosomes are protein-nucleic acid complexes. Phosphoproteins. These proteins have phosphate groups esterified to the hydroxyls of serine, threonine, or tyrosine residues. Casein, the major protein of milk, contains many phosphates and serves to bring essential phosphorus to the growing infant. Many key steps in metabolism are regulated between states of activity or inactivity, depending on the presence or absence of phosphate groups on proteins, as we shall see in Chapter 15. Glycogen phosphorylase a is one well-studied example. Metalloproteins. Metalloproteins are either metal storage forms, as in the case of ferritin, or enzymes in which the metal atom participates in a catalytically important manner. We encounter many examples throughout this book of the vital metabolic functions served by metalloenzymes. Hemoproteins. These proteins are actually a subclass of metalloproteins because their prosthetic group is heme, the name given to iron protoporphyrin IX (Figure 5.15). Because heme-containing proteins enjoy so many prominent biological functions, they are considered a class by themselves. Flavoproteins. Flavin is an essential substance for the activity of a number of important oxidoreductases. We discuss the chemistry of flavin and its derivatives, FMN and FAD, in the chapter on electron transport and oxidative phosphorylation