PROTEINS

 

PROTEINS

PREPARED BY MR. ABHIJIT DAS

DEFINITION

A protein is a large and complex molecule made up of chains of smaller units called amino acids. Proteins are essential for the structure, function, and regulation of cells and tissues in living organisms.

CLASSIFICATION OF PROTEINS (BASED ON COMPOSITION)

Proteins can be classified into two main categories based on their composition: simple proteins and conjugated proteins.

SIMPLE PROTEINS: Simple proteins are proteins that consist only of amino acids and do not contain any additional non-protein components. These proteins are made up of long chains of amino acids that are linked together by peptide bonds. Examples of simple proteins include albumins, globulins, and histones.

CONJUGATED PROTEINS: Conjugated proteins, also known as complex proteins, are proteins that contain one or more non-protein components in addition to amino acids. These non-protein components are called prosthetic groups. The prosthetic groups play a crucial role in the protein's structure and function. Examples of conjugated proteins include glycoproteins (proteins with attached carbohydrates, Ex- FSH/follicle-stimulating hormone), lipoproteins (proteins with attached lipids, Ex- LDL), and metalloproteins (proteins with attached metal ions, Ex- Haemoglobin). Conjugated proteins have diverse functions, such as cell signaling, membrane structure, and oxygen transport.

CLASSIFICATION OF PROTEINS (BASED ON SOLUBILITY)

Based on solubility, proteins can be classified into the following categories:

GLOBULAR PROTEINS: These proteins are soluble in water and other aqueous solutions. They have a compact, three-dimensional structure with hydrophilic amino acid residues on their surfaces, allowing them to interact with water molecules. Examples include enzymes, antibodies, and transport proteins.

FIBROUS PROTEINS: These proteins are often insoluble in water and other aqueous solutions. They have an elongated, filamentous structure with a high content of hydrophobic amino acid residues. Fibrous proteins provide structural support and are commonly found in connective tissues, such as collagen and keratin.

AMPHIPATHIC PROTEINS: These proteins have regions that are both hydrophilic and hydrophobic, making them partially soluble in water. They often have specific functions related to interactions with cell membranes or lipid environments. Examples include integral membrane proteins and some signaling proteins.

AMINO ACIDS

DEFINITION

Amino acids are organic compounds that serve as the building blocks of proteins. They are composed of an amino group (-NH2), a carboxyl group (-COOH), and a side chain (R group) attached to a central carbon atom. There are 20 different naturally occurring amino acids that are commonly found in proteins.

The amino group (-NH2) and the carboxyl group (-COOH) are functional groups that give amino acids their name. The side chain (R group) varies between different amino acids, and it determines the specific properties and characteristics of each amino acid.

CLASSIFICATION OF AMINO ACIDS (BASED ON CHEMICAL NATURE)

NONPOLAR AMINO ACIDS: Nonpolar amino acids have hydrophobic side chains that do not readily interact with water. They are typically insoluble in water and prefer to be in hydrophobic environments. Examples of nonpolar amino acids include:

Alanine (Ala, A)

Valine (Val, V)

Leucine (Leu, L)

Isoleucine (Ile, I)

Glycine (Gly, G)

Methionine (Met, M)

Phenylalanine (Phe, F)

Tryptophan (Trp, W)

Proline (Pro, P)

POLAR AMINO ACIDS: Polar amino acids have hydrophilic side chains that can interact with water molecules. They are generally more soluble in water compared to nonpolar amino acids. Examples of polar amino acids include:

Serine (Ser, S)

Threonine (Thr, T)

Cysteine (Cys, C)

Tyrosine (Tyr, Y)

Asparagine (Asn, N)

Glutamine (Gln, Q)

ACIDIC AMINO ACIDS: Acidic amino acids have side chains that are negatively charged at physiological pH due to the presence of a carboxyl group. They can act as acids by donating a hydrogen ion. Examples of acidic amino acids include:

Aspartic acid (Asp, D)

Glutamic acid (Glu, E)

BASIC AMINO ACIDS: Basic amino acids have side chains that are positively charged at physiological pH due to the presence of an amino group. They can act as bases by accepting a hydrogen ion. Examples of basic amino acids include:

Lysine (Lys, K)

Arginine (Arg, R)

Histidine (His, H)

ALCOHOLIC AMINO ACIDS: Alcoholic amino acids have side chains that contain hydroxyl groups (-OH). They are often involved in hydrogen bonding interactions. An example of an alcoholic amino acid is:

Threonine (Thr, T)

SULFUR-CONTAINING AMINO ACIDS: Sulfur-containing amino acids have side chains that contain sulfur atoms. The sulfur plays important roles in protein structure and function. Examples of sulfur-containing amino acids include:

Cysteine (Cys, C)

Methionine (Met, M)

AROMATIC AMINO ACIDS: Aromatic amino acids have side chains that contain an aromatic ring. They contribute to the hydrophobic core of proteins and play important roles in protein folding and stability. Examples of aromatic amino acids include:

Phenylalanine (Phe, F)

Tryptophan (Trp, W)

Tyrosine (Tyr, Y)

CLASSIFICATION OF AMINO ACIDS (BASED ON NUTRITIONAL REQUIREMENTS)

Amino acids can be classified based on their nutritional requirements into two main categories: essential amino acids and non-essential amino acids.

 

ESSENTIAL AMINO ACIDS: Essential amino acids are those that cannot be synthesized by the body in sufficient amounts and must be obtained from the diet. They are necessary for proper growth, development, and maintenance of bodily functions. There are nine essential amino acids:

 

Histidine

Isoleucine

Leucine

Lysine

Methionine

Phenylalanine

Threonine

Tryptophan

Valine

These essential amino acids need to be consumed through dietary sources, such as protein-rich foods like meat, poultry, fish, dairy products, legumes, and certain grains.

 

NON-ESSENTIAL AMINO ACIDS: Non-essential amino acids are those that the body can synthesize on its own, and they are not required to be obtained directly from the diet. While they can be synthesized, their production may still rely on the availability of essential amino acids or other precursor molecules. There are 11 non-essential amino acids:

 

Alanine

Arginine

Asparagine

Aspartic acid

Cysteine

Glutamic acid

Glutamine

Glycine

Proline

Serine

Tyrosine

FOUR LEVELS OF ORGANIZATION OF PROTEINS

PRIMARY STRUCTURE: The primary structure refers to the linear sequence of amino acids in a protein.

 

SECONDARY STRUCTURE: The secondary structure describes the local folding patterns within a protein. It is mainly stabilized by hydrogen bonding between the backbone atoms of amino acids. The two most common secondary structures are alpha helices and beta sheets. Alpha helices are tightly coiled structures resembling a spring, while beta sheets consist of extended strands connected by short stretches of amino acids.

 

TERTIARY STRUCTURE: The tertiary structure represents the three-dimensional arrangement of the entire protein molecule. It results from interactions between amino acid side chains, such as hydrogen bonding, disulfide bridges, hydrophobic interactions, and electrostatic interactions. The tertiary structure is responsible for the overall shape of the protein, determining its function and stability.

 

QUATERNARY STRUCTURE: Quaternary structure refers to the arrangement of multiple protein subunits (polypeptide chains) to form a functional protein complex. The subunits in a quaternary structure are held together by various interactions, such as hydrogen bonds, hydrophobic interactions, and disulfide bonds.

QUALITATIVE TESTS

BIURET TEST: The Biuret test is a commonly used test to detect the presence of proteins. It involves adding a reagent containing copper ions (such as copper sulfate) to the sample. In the presence of proteins, a violet color develops, indicating a positive result.

 

NINHYDRIN TEST: The Ninhydrin test is primarily used to detect the presence of amino acids, which are the building blocks of proteins. When amino acids react with ninhydrin, a purple or blue color develops. This color change indicates the presence of proteins.

 

XANTHOPROTEIC TEST: The Xanthoproteic test is another test used to detect the presence of proteins. It involves adding concentrated nitric acid to the sample. If proteins are present, a yellow color develops. Upon heating, the yellow color may turn orange.

 

MILLON'S TEST: Millon's test is used to detect phenolic compounds, such as tyrosine, which is an amino acid found in proteins. In this test, Millon's reagent (a solution of mercuric nitrate and nitrous acid) is added to the sample. A red color indicates the presence of phenolic compounds and hence proteins.

 

BIURET-MILLIGAN-MORGAN TEST: This test is a combination of the Biuret test and the Milligan-Morgan test. It is used to detect proteins in urine. The reagents used in this test include copper sulfate, potassium sodium tartrate, and sulfuric acid. The presence of proteins is indicated by the development of a purple or pink color.

BIOLOGICAL ROLE OF PROTEINS

1.     Enzymes: Many proteins act as enzymes, which are biological catalysts that facilitate and accelerate chemical reactions in the body. Enzymes play a vital role in metabolic pathways, breaking down substances, building new molecules, and regulating cellular processes.

 

2.     Structural Support: Proteins provide structural support and stability to cells and tissues. They form the framework of cells, tissues, and organs, maintaining their shape and integrity. For example, proteins like collagen and keratin are essential for the structure and strength of connective tissues, skin, hair, and nails.

 

3.     Transport and Storage: Certain proteins are responsible for transporting molecules, ions, and gases throughout the body. For instance, hemoglobin, a protein found in red blood cells, transports oxygen from the lungs to tissues. Similarly, carrier proteins facilitate the transport of specific molecules across cell membranes. Proteins can also serve as storage molecules, storing essential substances like iron (ferritin) or oxygen (myoglobin) until they are needed.

 

4.     Hormones and Signaling: Proteins act as chemical messengers in the form of hormones. Hormonal proteins, such as insulin, growth hormone, and adrenaline, regulate various physiological processes and maintain homeostasis in the body. Additionally, proteins are involved in cell signaling pathways, transmitting signals between cells and coordinating cellular responses.

 

5.     Immunity and Defense: Antibodies, a type of protein produced by the immune system, help defend the body against foreign substances (antigens) such as bacteria, viruses, and toxins. Antibodies recognize and neutralize these antigens, playing a critical role in the immune response.

 

6.     Muscle Contraction: Proteins, particularly actin and myosin, are responsible for muscle contraction. These proteins interact to generate the force required for muscle movement and locomotion.

 

7.     Regulation and Gene Expression: Proteins regulate gene expression by interacting with DNA and controlling the transcription and translation processes. Transcription factors, for example, bind to specific DNA sequences and influence the expression of genes, determining cell specialization and development.

 

8.     Enzyme Regulation: Proteins can regulate the activity of enzymes, modulating their function and controlling metabolic pathways. These regulatory proteins can activate or inhibit enzyme activity, ensuring that biochemical reactions occur at the appropriate rates and in response to specific signals.



METABOLISM OF AMINO ACIDS

DEAMINATION

Removal of an amino group (-NH2) from an amino acid.

TRANSAMINATION

Ø Transfer of an amino group (-NH2) from one molecule to another.

Ø This process is vital in the synthesis and breakdown of amino acids.

UREA CYCLE

Ammonia (NH3) is produced during the breakdown of amino acids.

1.     Carbamoyl Phosphate Formation: Ammonia combines with bicarbonate and ATP to form carbamoyl phosphate in a reaction catalyzed by carbamoyl phosphate synthetase I.  

2.     Citrulline Formation: Carbamoyl phosphate combines with ornithine to produce citrulline, with the help of the enzyme ornithine transcarbamylase.

3.     Argininosuccinate Formation: Citrulline reacts with aspartate to form argininosuccinate, with the assistance of the enzyme argininosuccinate synthetase.

4.     Arginine Formation: Argininosuccinate is cleaved to produce arginine and fumarate by argininosuccinate lyase.

5.     Urea Formation: Arginine is hydrolyzed to form urea and regenerate ornithine.

Urea is then excreted from the body primarily through the kidneys in the urine.

 

*EASY TO REMEMBER:

Ø Ammonia + Bicarbonate + 2 ATP → Carbamoyl Phosphate

Enzyme: Carbamoyl phosphate synthetase I

Ø Carbamoyl Phosphate + Ornithine → Citrulline

Enzyme: Ornithine transcarbamylase

Ø Citrulline + Aspartate → Argininosuccinate

Enzyme: Argininosuccinate synthetase

Ø Argininosuccinate → Arginine + Fumarate

Enzyme: Argininosuccinate lyase

Ø Arginine → Urea + Ornithine

Enzyme: Arginase

 

PHENYLKETONURIA

Phenylketonuria (PKU) is a metabolic disorder where the body can't properly process an amino acid called phenylalanine. This results in a build-up of phenylalanine in the body, which can lead to intellectual disabilities, developmental issues, and other health problems if not managed through a special diet.

ALKAPTONURIA

Alkaptonuria is a rare genetic disorder where the body can't properly break down the amino acids phenylalanine and tyrosine. This leads to a buildup of homogentisic acid, causing urine to turn dark when exposed to air.

JAUNDICE

1.     Yellow Skin and Eyes

2.     Excess Bilirubin in Blood

3.     Linked to Liver, Blood, or Bile Duct Issues

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