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Proteins (2)

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Page 1: Proteins (2)
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Definition Proteins are cellular macromolecules made

up of amino acid polymers (polypeptides). The sequence of amino acids, or primary structure of the protein, is dictated by the nucleotide sequence of the gene coding for that particular protein.

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ALL PROTEINS CONTAIN: * Carbon (C)            

* Oxygen (O)           * Nitrogen (N) * Hydrogen (H) * Sulfur (S)

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The word PROTEIN comes from Greek language (prota) which means "of primary importance". This name was introduced by Jons Jakob Berzelius in 1838 for large organic compounds with almost equivalent empirical formulas. This name was used because the studied organic compounds were primitive but seems to be very important for animal nutrition.

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Linear polymers of aa via amide linkages form peptides (1-10), polypeptides (11-100) and proteins (>100) eg; Aspartame (2), glutathione (3), vasopressin (9),insulin (51).

In the lab, proteins can be hydrolyzed (to aa)

by strong acid treatment.

Physiologic hydrolysis is by peptidases and proteases.

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The peptide bondProteins are made of amino acids linked into

linear chains, called polypeptide chains. Amino acids links between each other by peptide bonds - this peptide bond is formed between the carboxyl and amino groups of neighbouring amino acids. Proteins are formed by one or several polypeptide chains. The sequence of the polypeptide chain is defined by a gene with genetic code.

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General formula H O

| ||R – C – C – OH | NH2

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This process can then continue to join other amino acids and yield in an amino acid chain. When there are few amino acids in a chain, it is called an oligopeptide, when there are many it is called a polypeptide. Although the terms "protein" and "polypeptide" are sometimes used to describe the same thing, the term polypeptide is generally used when the molecular weight of the chain is below 10,000. An amino acid unit in a peptide is often called a residue.

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There are only 22 standard amino acids that exist in living organism. Sometimes these amino acids are chemically modified in the protein after protein synthesis. In total the number of different proteins, which it is possible to produce from 22 amino acids is enormous. For example for 10 amino acid sequence it is possible to have 2010 different sequences, which is approximately equal to 1013 or 10 trillions of different structures.

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Generally speaking, proteins do everything in the living cells. All functions of the living organisms are related with proteins. Each protein or group of proteins are responsible for their own specific function.

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Post-translational modifications

After a protein is synthesized inside the cell ,is usually modified by addition of extra functional groups to the polypeptide chain. These can be sugar or phosphate groups and may confer to the protein special functions such as: the ability to recognize other molecules, to integrate in the plasma membrane, to catalyze biochemical reactions, and various other processes.

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CLASSIFICATION OF PROTEINS BY COMPOSITIONSimple Proteins

Albumins: blood (serum albumin); milk (lactalbumin); egg white (ovalbumin); lentils (legumelin); kidney beans (phaseolin); wheat (leucosin).

Globular protein. Soluble in water and dilute salt solution;

precipitated by saturation with ammonium sulfate solution; coagulated by heat; found in plant and animal tissues.

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Globulins: blood (serum globulins); muscle (myosin); potato (tuberin); Brazil nuts (excelsin); lentils (legumin).

Globular protein; sparingly soluble in water; soluble in neutral solutions; precipitated by dilute ammonium sulfate and coagulated by heat; distributed in both plant and animal tissues.

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Glutelins: wheat (glutenin); rice (oryzenin). Insoluble in water and dilute salt solutions; soluble in dilute acids; found in grains and cereals.

Prolamines: wheat and rye (gliadin); corn (zein); barley (hordein). Insoluble in water and absolute alcohol; soluble in 70% alcohol; high in amide nitrogen and proline; occurs in grain seeds.

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Protamines: sturgeon (sturine); mackerel (scombrine); salmon (salmine); herring (clapeine). Soluble in water; not coagulated by heat; strongly basic; high in arginine; associated with DNA; occurs in sperm cells.

Histones: Thymus gland; pancreas; nucleoproteins (nucleohistone). Soluble in water, salt solutions, and dilute acids; insoluble in ammonium hydroxide; yields large amounts of lysine and arginine; combined with nucleic acids within cells.

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Scleroproteins: Connective tissues and hard tissues. Fibrous protein; insoluble in all solvents and resistant to digestion. Collagen: connective tissues, bones, cartilage,

and gelatin. Resistant to digestive enzymes but altered to gelatin by boiling water, acid, or alkali; high in hydroxyproline.

Elastin: Ligaments, tendons, and arteries. Similar to collagen but cannot be converted to gelatin.

Keratin: Hair, nails, hooves, horns, and feathers. Partially resistant to digestive enzymes; contains large amounts of sulfur, as cystine.

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Conjugated Proteins

Nucleoproteins: cytoplasm of cells (ribonucleoprotein); nucleus of chromosomes (deoxyribonucleoprotein) viruses, and bacteriophages. Contains nucleic acids, nitrogen, and phosphorus. Present in chromosomes and in all living forms as a combination of protein with either RNA or DNA.

Mucoprotein: saliva (mucin); egg white (ovomucoid). Proteins combined with amino sugars, sugar acids, and sulfates.

Glycoprotein: bone (osseomucoid); tendons (tendomucoid); carilage (chondromucoid).

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Phosphoproteins: milk (casein); egg yolk (ovovitellin). Phosphoric acid joined in ester linkage to protein.

Chromoproteins: hemoglobin; myoglobin; flavoproteins; respiratory pigments; cytochromes. Protein compounds with some nonprotein pigments as heme; colored proteins.

Lipoproteins: serum lipoprotein; brain, nerve tissues, milk, and eggs. Water-soluble protein conjugated with lipids; found dispersed widely in all cells and all living forms.

Metalloproteins: ferritin; carbonic anhydrase; ceruloplasmin. Proteins combined with metallic atoms that are not parts of a nonprotein prosthetic group.

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Derived Proteins

Proteans: edestan (from elastin) and myosan (from myosin). Results from short action of acids or enzymes; insoluble in water.

Proteases: intermediate products of protein digestion. Soluble in water; uncoagulated by heat; and precipitated by saturated ammonium sulfate; result from partial digestion of protein by pepsin or trypsin.

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Peptones: intermediate products of protein digestion. Same properties as proteases except that they cannot be salted out; of smaller molecular weight than proteases.

Peptides: intermediate products of protein digestion. Two or more amino acids joined by a peptide linkage; hydrolyzed to individual amino acids.

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CLASSIFICATION BASED UPON FUNCTION

Enzymes (catalytic proteins) Lactase, ribonuclease, pyruvate dehydrogenase, fumarase, proteinase

Structural proteins Collagen, elastin, keratin Regulatory or hormonal proteins Insulin,

adrenaline Transport proteins Hemoglobin, myoglobin Genetic proteins Nucleoproteins, histones Immune Proteins Gamma Globulin, Ig's, (Ab's) Contractile Proteins Actin, myosin Storage Proteins Zein, ovalbumin, casein

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Classification by protein functions

Proteins are responsible for many different functions in the living cell. It is possible to classify proteins on the basis of their functions. Very often, proteins can carry few functions and such proteins can be placed into different groups, but despite this, it is possible to assign main group for each protein.

Enzymes - proteins that catalyze chemical and biochemical reactions within living cell and outside. This group of proteins probably is the biggest and most important group of the proteins. Enzymes are responsible for all metabolic reactions in the living cells. Well known and very interesting examples are: DNA- and RNA-polymerases, dehydrogenases etc.

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Hormones - proteins that are responsible for the regulation of many processes in organisms. Hormones are usually quite small and can be classifies as peptides. Most known protein hormones are: insulin, growth factor, prolactin etc.

Many protein hormones are predecessor of peptide hormones, such as endorphin, enkephalin etc.

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Transport proteins - These proteins are transporting or store some other chemical compounds and ions. Some of them are well known: cytochrome C - electron transport; haemoglobin and myoglobin - oxygen transport; albumin - fatty acid transport in the blood stream etc. It is possible to classify trans membrane protein channels as a transport proteins as well.

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Immunoglobulin or Antibodies - proteins that involved into immune response of the organism to neutralize large foreign molecules, which can be a part of an infection. Sometimes antibodies can act as enzymes. Sometimes this group of proteins is considered as a bigger group of protective proteins with adding such proteins as lymphocyte antigen-recognizing receptors, antivirals agents such as interferon, tumor necrosis factor (TNF). Probably the clotting of blood proteins, such as fibrin and thrombin should be classified as protective proteins as well.

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Structural proteins - These proteins are maintain structures of other biological components, like cells and tissues. Collagen, elastin, α-keratin, fibrin - these proteins are involved into formation of the whole organism body. Bacterial proteoglycans and virus coating proteins also belongs to this group of proteins. Currently we do not know about other functions of these proteins.

Motor proteins. These proteins can convert chemical energy into mechanical energy. Actin and myosin are responsible for muscular motion. Sometimes it is difficult to make a strict separation between structural and motion proteins.

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Receptors These proteins are responsible for signal detection and translation into other type of signal. Sometimes these proteins are active only in complex with low molecular weight compounds. Very well known member of this protein family is rhodopsin - light detecting protein. Many receptors are transmembrane proteins.

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Signalling proteins - This group of proteins is involved into signalling translation process. Usually they significantly change conformation in presence of some signalling molecules. These proteins can act as enzymes. Other proteins, usually small, can interact with receptors. Classical example of this group of proteins is GTPases.

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Storage proteins. These proteins contain energy, which can be released during metabolism processes in the organism. Egg ovalbumin and milk casein are such proteins. Almost all proteins can be digested and used as a source of energy and building material by other organisms.

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Classification of proteins by location in the living cellProtein classification can be based on their

appearance in the living cell. According to this, it is possible to classify all proteins into four main groups.

Membrane or transmembrane proteins - these proteins are located within cell membrane lipid bi-layer. These proteins can be completely or partially buried in membrane.

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Internal proteins - these proteins are located within living cell and all functions are related with intercellular needs.

External proteins - these proteins function outside the cell in which they are produced. Such type of proteins is more common for multicellular organisms.

Virus proteins - These proteins are present only in virus organism, usually as a coat for viral particle.

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CLASSIFICATION BASED UPON SHAPE

Fibrous Proteins - Long thread-like molecules whose helical strands often form fibers or sheets; often insoluble in water. e.g; Collagen, elastin, keratin

Globular Proteins - Generally soluble in aqueous media; spheroid or ovoid shape; further classified on the basis of solubility - water soluble, heat coaguble, include proteins in blood serum, egg white, milk, and in certain plants (pea, wheat);soluble in dilute salt solutions

include proteins in blood serum, egg white, and in plants such as peanuts.

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CLASSIFICATION BASED UPON PHYSICOCHEMICAL PROPERTIES

Simple Proteins - Yield only amino acids on hydrolysis Albumins, Globulins, Glutelins Soluble in dilute

acids and alkalies Scleroproteins Nonsoluble proteins such as Collagen Prolamines Soluble in alcohol, insoluble in water;

found in seeds of plants Histones Soluble in water, dilute acids, and alkalies;

contain a large portion of basic amino acids such as globin of hemoglobin

Protamines Basic proteins which are essentially large polypeptides

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Conjugated Proteins Yield amino acids and nonprotein products upon hydrolysis Glyco- or mucoproteins Proteins plus

carbohydrates; e.g. mucin of saliva Lipoproteins Proteins plus a lipid; e.g.

lipovitellin of egg yolk Chromoproteins Proteins plus a pigmented

prosthetic group e.g. hemoglobin, myoglobin Metalloproteins Proteins plus a metal element

such as iron, magnesium, copper, or zinc; e.g. ferritin (Fe), tyrosine oxidase (Cu), alcohol dehydrogenase (Zn).

Nucleoproteins Proteins plus nucleic acid; e.g. nucleohistone

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Classification of proteins by posttranslational modification

After protein translation some of them are subjected to posttranslational modification. This modification can be related with many different aspects of changes. Again this classification split all proteins into overlapped groups.

Native proteins - these proteins are not changed after translation.

Glyco-proteins - these proteins are modified by covalent binding with linear or branched oligosaccharides.

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Cleaved proteins - the polypeptide chain of these proteins are cleaved into two or more pieces.

Proteins with disulphide bonds. In these proteins pair of cysteins are linked between each other by S-S or disulphide bond (disulphide bridge)

Protein complexes. Some proteins produce protein complexes of homo- and hetero- nature.

Chemically modified proteins - in these proteins some residues are chemically modified by covalent bonding with other chemical compounds.

Prions - these proteins are folded wrongly during translation, or change their configuration straight after translation.

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Protein Functions

Antibodies - are specialized proteins involved in defending the body from antigens (foreign invaders). One way of antibody destroying antigens is by immobilizing them so that they can be destroyed by white blood cells.

Contractile Proteins - are responsible for movement. Examples include actin and myosin. These proteins are involved in muscle contraction and movement.

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Enzymes - are proteins that facilitate biochemical reactions. They are often referred to as catalysts because they speed up chemical reactions. Examples include the enzymes lactase and pepsin. Lactase breaks down the sugar lactose found in milk. Pepsin is a digestive enzyme that works in the stomach to break down proteins in food.

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Hormonal Proteins - are messenger proteins which help to coordinate certain bodily activities. Examples include insulin, oxytocin, and somatotropin. Insulin , oxytocin, and somatotropin. Insulin regulates glucose metabolism by controlling the blood-sugar concentration. Oxytocin stimulates contractions in females during childbirth. Somatotropin is a growth hormone that stimulates protein production in muscle cells.

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Structural Proteins - are fibrous and stringy and provide support. Examples include keratin, collagen, and elastin. Keratins strengthen protective coverings such as hair, quills, feathers, horns, and beaks. Collagens and elastin provide support for connective tissues such as tendons and ligaments.

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Storage Proteins - store amino acids. Examples include ovalbumin and casein. Ovalbumin is found in egg whites and casein is a milk-based protein.

Transport Proteins - are carrier proteins which move molecules from one place to another around the body. Examples include hemoglobin and cytochromes. Hemoglobin transports oxygen through the blood. Cytochromes operate in the electron transport chain as electron carrier proteins.

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PLASMA PROTEIN SYNTHESIS SITE

Hepatic/Liver = almost all proteins; except Gamma Globulins

* Plasma Cells = immunoglobulins

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TOTAL PROTEIN: REFERENCE RANGESerum        6.0 - 8.0 gm/dl

CSF            15  - 45 mg/dl Urine          negative - trace

dl = 100 mL = %

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CLINICAL SIGNIFICANCE Hyperproteinemia

Hemolysis = Falsely INCREASES (RBC proteins released into Serum)

Increased Total Protein - Dyhydration/Vomitting/Diarrhea - most common cause - Multiple Myeloma - immunoglobulin disease state

- Excessive Hormone Secretions - example: increased aldosterone

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HypoproteinemiaDecreased albumin synthesis:

a.Liver disease (specially chronic diseases).b.Malnutrition.c.AlcoholismIncreased albumin loss:

a.Renal disease (nephrotic syndrome). Loss of albumin in urine (proteinuria).b.Extensive burns: Loss of albumin through skin .

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Prion Diseases Prion diseases or transmissible spongiform

encephalopathies (TSEs) are a family of rare progressive neurodegenerative disorders that affect both humans and animals. They are distinguished by long incubation periods, characteristic spongiform changes associated with neuronal loss, and a failure to induce inflammatory response.

The causative agents of TSEs are believed to be prions. The term "prions" refers to abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins that are found most abundantly in the brain. The functions of these normal prion proteins are still not completely understood. The abnormal folding of the prion proteins leads to brain damage and the characteristic signs and symptoms of the disease. Prion diseases are usually rapidly progressive and always fatal.