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Saturday, January 28, 2023

Proteins| classification | structure and organization| deficiency diseases of proteins|

    PROTEINS    

Proteins are the highly complex chemical compounds present in all living organism. These are the high molecular weight polypeptides, composed of carbon, hydrogen, oxygen, nitrogen, Sulphur and phosphorus. Proteins are the most abundant and essential constituents of living cells. All the basic functions of life depend upon specific proteins. The term protein was first suggested by Swedish chemist Berzelius in 1938 and derived from the Greek word “proteins” meaning ‘first’. Gerardus Mulder for the first time used the term in 1840 and referred it to the complex organic nitrogenous substance found in the cells of living organisms. Proteins are the most significant compound in living beings depending upon their chemical and physical structures they are involved in wide variety of functions i.e. catalysis, conduction, contraction, structure, nutrition, binding and defense.

Chemical Structure of Proteins: -

Proteins are the linear polymers of amino acids. Proteins can be very long polypeptide chains of hundred to several thousand amino acids. When a large number of amino acids join together, they form polypeptides chains. The amino acids molecules in polypeptide chains are linked by polypeptide bonds. 

[Amino Acid] n → Peptide → Polypeptide → Protein

Peptide Bond: The amino acids of a protein are joined to one another by their respective amino and carboxyl groups i.e. the carboxyl group of one amino acid is joined to the amino group of the next amino acid to form a peptide bond or peptide linkage with the release of one molecule of water.

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Fig: - formation of peptide bond

CLASSIFICATION OF PROTEINS: -

Proteins can be classified according to their functions, shape, structures and complexity. On the basis of their conformation the proteins can be classified into two major 

1). Fibrous proteins

2). Globular Proteins 

1). Fibrous proteins: - 

In fibrous proteins polypeptide chains are arranged in a parallel manner along a single axis producing long fibers or sheet like structures. Fibrous proteins Fibrous proteins are insoluble inwater or dilute salt solution. These are the basic structural elements in animal tissues. Keratin of hair and skin, elastin of ligament and collagen of tendons and bone matrix all are examples of fibrous proteins.

2). Globular Proteins: - 

Polypeptide chains are tightly folded into compact spherical or globular shapes. Most of the globular proteins are soluble in water example of globular proteins are all the enzymes, certain hormones, and antibodies etc. 

On the basis of their structure and complexity proteins are classified into three major classes: -

1). Simple proteins 

2). Conjugated or Complex proteins 

3). Derived proteins 

1). Simple proteins: - Proteins which consist solely of amino acid are called simple proteins. These are further classified into the following subclasses: -

Albumins: They are soluble in water and coagulate on heating. They are precipitated by dilute acids and alkalis. Albumins are widely distributed in nature stored as food reserved e.g. egg albumin, serum albumin, legumin (legumes), lactalbumin (milk), leucosin (cereals), gliadin (wheat). 

Protamine: They are basic proteins highly soluble in water, dilute acids and ammonium hydroxide. Protamine are not coagulated by heat. These are simplest of all the naturally occurring. proteins, isolated from mature sperms e.g. Sturine and salmine. 

Histones: These are soluble in water and dilute acids but insoluble in ammonia. They are not coagulated by heat. Histones occur as part of nucleoproteins. 

Scleroproteins: These are also known as albuminoids. Scleroproteins are soluble in water and solutions of neutral salts. They are found exclusively in animals e.g. keratin, collagen, elastin and fibroin.

Globulins: These are insoluble in water but are soluble in dilute neutral salt solution such as NaCl. On heating globulin get coagulated. They are precipitated by half saturated with ammonium sulphate examples of globulins are fibrinogen (blood plasma), egg globulin, myogenic (muscles), legumin (peas), tuberin (potato) etc. 

Glutelins: They are insoluble in water but are soluble in dilute acids and Alkalies, Glutelin get coagulate on heating. These are found exclusively in seeds of cereal grains e.g. glutenin (wheat) and oxyzenin (rice). 

Prolamins: These are insoluble in water but are soluble in dilute alkalies and 50-80% of alcohol. They are not coagulated by heat and found in plants only e.g. hordein (barley), gliadin (wheat) and zein (maize)

2. Conjugated Proteins: -These proteins are composed of not only amino acids but also some nonproteins components. This non-protein substance linked to proteins is called “prosthetic group”. Conjugated proteins are further classified into the following subclasses on the basis of their prosthetic group.

Glycoproteins: In glycoproteins simple proteins are covalently linked with carbohydrate group. The percent of carbohydrate group in different glycoproteins may vary from less than1% in egg albumin to as high as 80% in mucoproteins. Glycoproteins which have very high carbohydrate content are called proteoglycans. Examples of glycoproteins are mucin (saliva), heparin (bile juice), and immunoglobulins (plasma). 

Nucleoproteins: In nucleoproteins protein molecules are combined with nucleic acid. The chromatin material of the nuclei of cells is composed of nucleoproteins e.g. nucleohistones. 

Lipoproteins: Lipoproteins are the proteins in combination with lipids. These are present in the brain, egg, milk and plasma.

Phosphoproteins: Phosphoproteins are formed by the combination of simple proteins with phosphoric acid. Examples of phosphoproteins are vitelline (egg) and casein (milk). 

Metalloproteins: These are proteins linked to some metallic prosthetic group, which also gives colour to the proteins. They are also known as chromoproteins e.g. hemoglobin, hemocyanin, cytochromes and flavoproteins.

3. Derived Proteins: These proteins are derived from some previously existing proteins either by its hydrolysis or by its coagulation. Derived proteins can be divided into two major subclasses.

 Primary derived proteins: - These are denaturized or coagulated proteins. The denaturation is caused by heat, acid or alkali treatment. Their molecular weight is same as the native protein, but they differ in solubility, precipitation and crystallization. Examples are proteins, metaproteins, and coagulated proteins.

Secondary derived proteins:- These are formed by the hydrolysis of complex protein of their peptide linkage. The hydrolysis is caused by the action of digestive enzymes, acids or alkalis. Their molecular weight is different from the native proteins. Examples are proteoses, peptones and peptides. On the basis of their biological functions they are classified into seven major classes: 

i) Structural Proteins: Their function is strengthening or protecting biological structures e.g. keratin, fibroin, collagen, elastin etc. 

ii. Storage and Nutrient Proteins: Their function is to provide nourishment to growing e.g. ovalbumin, giadin, ferritin etc.

iii. Enzymatic Proteins: Their function is to transport molecules in body e.g. hemoglobin,serum albumin, myoglobin etc.

iv. Transport Proteins: Their function is to transport molecules or ions in body e.g. haemoglobin, myoglobin and serum albumin.

v. Regulatory Proteins: Their function is to regulate cellular or metabolic activities e.g. hormones, repressors etc.

vi. Contractile Proteins: Their function is in contractile system e.g. actin, myosin, tubulin, etc.

vii. Defense Proteins: Their function is to provide defense against other organisms e.g. antibodies, ricin etc.

Structural Organization of Proteins: -

Proteins are long polypeptide chains formed by the linkages of several thousand molecules of amino acid with a peptide bond. Proteins can be very long polypeptide chains of 100 to several thousand amino acid residues. There are four different structural level of organization are present in proteins, they are:

1). Primary structure

2). Secondary structure

3). Tertiary structure

4). Quartiary structure

GENERAL PROPERTIES OF PROTEINS: - 

SOLUBILITY 

The solubility of protein varies to the native because proteins are colloids of large-sized molecules these form turbine solution in water. These are also soluble in acid and salt solution while insoluble in alcohol. 

AMPHOTERIC NATURE: -

Like a-acid proteins are amphoteric in nature. They behave as acid alkaline solution and alkaline to acidic solution due to presence of several free- NH2 and COOH groups.

ZWITTERION FORMATION: - 

The protein is either positively or negatively charged molecule and in an electric field migrate either towards cathode or towards anode. They are electrically neutral and do not move towards any pole. 

HYDROLYSIS: -

 The protein undergoes hydrolysis by acid, alkali or hydrolytic enzymes which lead the protein to amino acids. Complete hydrolysis with HCl or H2SO4 and yields free a-acid thin breakdown products. 

DENATURATION 

Under certain conditions there is a disruption of secondary tertiary and quaternary structures of functional protein molecule resulting in the changes of its physical, chemical and biological characteristics. These changes occurring in proteins are collectively called denaturation. During denaturation only primary structure of protein is retained. Various physical and chemical elements such as heat, UV-rays, X-rays, ultrasonic waves, high pressure, acids, alkalis, detergents or certain organic solvents can cause denaturation of proteins. Physical and chemical properties of denatured proteins are different then the native proteins and they lose most of their biological activities, in denatured proteins the solubility is decreased or lost. During denaturation the soluble globular proteins are changed into insoluble fibrous proteins. The process of denaturation also destroys enzyme and hormonal activity and the proteins become biologically inactive. The process of denaturation in some proteins is returned to its native stable confirmation and regains their native structure and biological activity, this process is called renaturation.

METABOLISM OF PROTEINS 

Amino acids are the building blocks of proteins and proteins are the building material in the body. Metabolism of proteins involves both biosynthesis of amino acids as well as breakdown of amino acids. 

BIOSYNTHESIS OF AMINO ACID 

There are 20 standard amino acids known and these can be classified into the group on the basis of their synthesis in human and animals are called the non-essential amino acid whereas the amino acid which cannot be synthesized by the organisms, and they must be obtained through diet are called the essential amino acids. The pathways for the synthesis of these two types of amino acids are quite different. Non essential amino acids can be synthesized by quite simple reaction while synthesis of essential amino acids is quite complex. 

CATABOLISM OF AMINO ACIDS 

Amino acids are not only served as the building blocks of proteins but also serve as source of carbon and nitrogen, when required. The very first step in their catabolism is removal of –NH2 group and formation of corresponding keto-acid. The ammonia, which is liberated, quickly converted to urea and it is incorporated in some other a-acid. Catabolism of a-acid involves the following process:

1. Transamination

2. Deamination

3. Urea formation

4. Decarboxylation

Transamination: Russian workers Braunstein and Bychkov had shown the importance of transamination for the first time in 1939. It is the most important process of conversion of amino acid into keto acid. In this process amino group of one amino acid (donor) is transferred to an αketo acid (recipient) resulting in the formation of a new amino acid and a new keto acid. The donor amino acid is converted into a new keto acid and the recipient keto acid is converted into a new amino acid. Transamination is a reversible process and is catalyzed by the enzyme transaminase or amino transferase. Co-enzyme for the reaction is pyridoxal-5’-phosphate, a derivative of vitamin B6 (Pyridoxine). Transamination takes place principally in liver, kidney, heart and brain. Deamination: Deamination is a process in which amino group (-NH2) is removed from the amino acid, which then changes to a α-keto acid. In this process amino group is removed as ammonia. Deamination usually takes place in liver and kidney cells to catabolize excess of amino acids. 

There are two types of deamination:

i. Oxidative deamination

ii. Non oxidative deamination

✅Oxidative Deamination: When deamination process is accompanied by an oxidative reaction, is known as oxidative deamination. This process is catalyzed by a group of flavin containing enzymes known as amino acid oxidases. This is the two step reaction, in the first step the amino acid is dehydrogenated by the flavoprotein of the enzyme. In the next step with addition of H acid is formed. The enzyme amino acid oxidase is auto oxidizable flavoprotein. Reduced flavoprotein is oxidized to form hydrogen peroxide, which then broken up into H catalase.

Non oxidative Deamination: There are certain amino acids which can be deaminated non oxidatively. Non oxidative deamination is catalyzed by specific enzymes and NH3 is liberated in this process. One example of non-oxidative deamination is deamination of glutamate by the enzyme glutamate dehydrogenase. This reaction is reversible in which NAD act as coenzyme. Fate of Deaminated Amino Acids: Acids produced from transamination and deamination of amino acids are channeled to several metabolic routes. Some amino acids are deaminated to produce keto acids which are eventually oxidized to CO2 and H2O through acetoacetate and acetyl-co-A.  Aceto acetone is one of the chemical constituents of ‘ketone bodies’ formed in the pathological conditions of urine. 

Thus the amino acid which leads to the formation of acetoacetate during their metabolism are called ketogenic e.g. leucine & lysine Some amino acids are deaminated to produce keto acids which are broken down to pyruvate, α-keto glutamate, succinyl co-A, fumarate or oxaloacetate which can be utilized for the synthesis of glucose or glycogen. This amino acid is called glycogenic or antiketogenic amino acid example of glucogenic amino acids are called glucogenic or antiketogenic amino acids. Examples of glucogenic amino acids are alanine, glycine, serine, aspartate, glutamate, valine, histidine Argene, proline, methionine, cystine and arginine. Some amino acids are precursors of both glucose and ketone bodies are known as glucogenic and ketogenic amino acids. Examples are phenylalanine, tyrosine, isoleucine, threonine and tryptophan. Fate of Ammonia: Ammonia released during deamination is either converted into ammonium salt or into urea.

Formation of ammonium salts: -Ammonium ions (NH4+) are formed from some of the ammonia released by deamination of amino acids. These ammonium ions are excreted out from the body in the form of ammonium salts.

Formation of Urea (Urea cycle): When production of ammonia exceeds beyond a certain level it become toxic. Excess of ammonia produced during the deamination of amino acids is converted to less toxic substance, urea, before been excreted in the urine. Formation of urea is a cyclic process and the cycle is known as urea cycle. This cycle was first outlined by Hans Krebs and Kurt Henslie in 1932; hence it is also known as Kreb’s Hanseleit cycle. The chief site for urine formation is liver and after its formation urea passes into the blood Strem and form blood to kidneys s and finally excreted into the urine. Urea synthesis takes place in five steps. Each step is catalyzed by a specific enzyme. Out of these five enzymatic reactions, two take place in the mitochondria and three take place in the cytoplasm. This cycle is also known as ornithine cycle as it involves conversion of amino acid ornithine to citrulline though glutamic acid which is derived from aspartic acid by transamination and/or form α- ketoglutaric acid and ammonia.

Decarboxylation: Decarboxylation is the process in which CO2 is removed from the carboxyl group of an amino acid resulting the formation of an amine. Enzyme aminoacidic decarboxylases catalase these reactions which require pyridoxal phosphate as coenzyme. For example, histidine is decarboxylated to histamine by histidine decarboxylase and 3,4- dihydroxyphenylalanine is decarboxylated to dopamine. These types of amines are called, biogenic amines. Many of these amines have strong pharmacological effects and others are important as precursors of hormones or as co-enzymes.

SOURCES OF PROTEINS 

Proteins are widely distributed in plants and animals. Common sources of proteins are milk, yogurt, cheese, fishes, beans, nuts, green peas, meat, eggs, lentils, soy products, quinoa and sea foods.

BIOLOGICAL SIGNIFICANCE OF PROTEINS 

Proteins are the most significant macromolecules in living beings because of the following physiological roles performed by them in all biological processes:

1. Proteins which are involved in the formation and maintenance of various cellular structures are called structural proteins. These proteins form an important part of all membranes and membrane bound organelles of the cell. The cell wall and primary fibrous of the cell have structural proteins e.g. Collagen is the most abundant fibrous protein found in animals forming a major part of the skin, cartilage, ligament, tendons and bones. Keratin is another animal protein involved in the formation of scales, hair, feather, horns, hoofs, fur wool, nails and claws.

2. Capacity of motion and flexibility in the organisms is due to the presence of certain proteins called contractile proteins e.g. Muscle proteins- actin and myosin.

3. Proteins acts as enzymes or biocatalysts and catalyzes a variety of chemical reactions in the living organisms. Almost all the enzymes are protein in nature.

4. Some proteins bind and transport specific types of molecules via blood e.g. hemoglobin is important protein, transports oxygen from lungs to cell tissues. Myoglobin binds and transports oxygen in the muscles. Certain membrane proteins transport ions and small molecules across the cell membrane.

5. Some proteins are stored as reserve food such as albumin in egg and glutelin in rice. In the liver ferritin stores iron.

6. A few proteins functions as hormone e.g. insulin.

7. Proteins also play important role in the immune system of vertebrates. Antibodies are immunoglobulins which combine and neutralize the antigen entering the body.

8. Proteins also take part in blood coagulation e.g. thrombin and fibrinogen.

DEFICIENCY DISEASES OF PROTEINS 

Protein deficiency can lead to weak muscle tone, thin and brittle hair, edema or swelling, skin lesions, fatigue, stunted growth and cognitive development as well as mental health in children. Following diseases can occur due to protein deficiency: 

Marasmus: It affects infants and very young children, often resulting in weight loss and dehydration. People with marasmus appear bony with little muscle tissue.


Kwashiorkor: It usually affects older children. People with Kwashiorkor appear swollen stomach due to fluid retention.

Cachexia: It is a condition that involves protein deficiency, depletion of skeletal muscle and an increased rate of protein degradation. It causes weight loss and mortality and is associated with cancer, AIDS, heart disease and chronic kidney failure.











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