PROTEINS (BSc. NURSING)

PROTEINS

PREPARED BY MR. ABHIJIT DAS

A protein is a polymer composed of amino acids, with each amino acid acting as a monomer. These amino acids are bonded together by peptide bonds to form chains, which then fold into complex three-dimensional structures to create functional proteins.

AMINO ACIDS:

Amino acids are the fundamental molecules that make up proteins. They consist of an amino group (-NH2), a carboxyl group (-COOH), a hydrogen atom, and a side chain (R group) attached to a central carbon atom. These molecules are linked together by peptide bonds to form protein chains.

CLASSIFICATION OF AMINO ACIDS BASED ON NUTRITION

Amino acids can be classified based on their nutrition into two main categories:

1.     Essential amino acids: These are amino acids that cannot be synthesized by the human body and must be obtained from the diet. There are nine essential amino acids: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. These amino acids are crucial for protein synthesis and various physiological functions.

2.     Non-essential amino acids: Non-essential amino acids are those that the human body can synthesize on its own, so they do not need to be obtained from the diet. There are eleven non-essential amino acids: alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, proline, serine, and tyrosine. Although they are synthesized in the body, some non-essential amino acids may become conditionally essential during times of illness, stress, or other physiological conditions.

CLASSIFICATION OF AMINO ACIDS BASED ON METABOLIC RATE

Amino acids can also be classified based on their metabolic fate or rate of degradation within the body. There are two primary classifications:

1.     Glucogenic amino acids: These amino acids can be converted into glucose through a process called gluconeogenesis. Glucogenic amino acids include alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, histidine, methionine, proline, serine, and valine.

2.     Ketogenic amino acids: Ketogenic amino acids can be converted into ketone bodies. These amino acids primarily contribute to the production of energy through ketogenesis rather than glucose synthesis. The ketogenic amino acids are leucine and lysine, although lysine is considered to be weakly ketogenic.

DIGESTION OF PROTEINS:

Digestion of proteins is a complex process that begins in the stomach and continues in the small intestine.

1.     Stomach:

·         Pepsinogen (inactive form), an inactive enzyme produced by the stomach, is converted into pepsin (active form) by the acidic environment. Pepsin is a protease enzyme that starts breaking down proteins into smaller peptides.

2.     Small Intestine:

·         The partially digested food (chyme) moves into the small intestine where it encounters a less acidic environment.

·         Pancreatic enzymes such as trypsin, chymotrypsin, elastase and carboxypeptidase are released from the pancreas into the small intestine. These enzymes further break down the partially digested proteins into smaller peptides.

·         The cells lining the small intestine also produce enzymes called peptidases, which further break down peptides into amino acids.

ABSORPTION OF AMINO ACIDS:

• Amino acids, the building blocks of proteins, are absorbed by the cells lining the small intestine via active transport (by using ATP) mechanisms.
• Dipeptides and tripeptides are transported into the enterocytes by specific transporters, where they are further broken down into amino acids before being absorbed into the bloodstream.

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

 

BIOLOGICALLY IMPORTANT COMPOUNDS SYNTHESIZED FROM VARIOUS AMINO ACIDS:

1.     Enzymes: Enzymes are proteins that catalyze biochemical reactions in living organisms. They play crucial roles in metabolism, digestion, and cellular processes. Enzymes are composed of amino acid chains.

2.     Neurotransmitters: Neurotransmitters are chemical messengers that transmit signals between nerve cells (neurons) in the nervous system. Examples include serotonin, dopamine, and gamma-aminobutyric acid (GABA). Serotonin is derived from the amino acid tryptophan, while dopamine and norepinephrine are derived from the amino acid tyrosine.

3.     Hormones: Hormones are signaling molecules that regulate various physiological processes in the body.

4.     Collagen: Collagen is the most abundant protein in the human body and is a major component of connective tissues such as tendons, ligaments, and skin. It provides strength and structure to tissues. Collagen is composed of amino acids, primarily glycine, proline, and hydroxyproline.

5.     Antibodies: Antibodies are proteins produced by the immune system in response to foreign substances (antigens) such as bacteria and viruses. They help neutralize and eliminate pathogens. Antibodies are composed of amino acid chains and are highly specific to their target antigens.

6.     Creatine: Creatine is a nitrogenous organic compound that plays a key role in energy metabolism, particularly in muscles. Creatine phosphate serves as a rapid source of ATP (adenosine triphosphate) for muscle contraction.

7.     Receptors: Receptors are proteins located on the surface of cells or within cells that bind to specific molecules (ligands) and initiate a cellular response. Receptors are composed of amino acids arranged in specific configurations to recognize and bind to their ligands.

8.     Ion channels: Ion channels are membrane proteins that form pores in cell membranes, allowing the passage of ions (such as sodium, potassium, calcium, and chloride) across the membrane. They play essential roles in maintaining cellular homeostasis, electrical signaling, and nerve impulse transmission.

9.     Hemoglobin: Hemoglobin is composed of four protein subunits, each of which is a globin protein. Globin proteins are a family of heme-containing proteins that are involved in binding and transporting oxygen.

IN BORN ERRORS OF AMINO ACID METABOLISM:

Inborn errors of amino acid metabolism refer to a group of genetic disorders that impair the body's ability to properly process specific amino acids. Among these disorders, the ones specifically related to aromatic amino acids are:

1.     Phenylketonuria (PKU): PKU is a metabolic disorder caused by a deficiency in the enzyme phenylalanine hydroxylase, which is responsible for converting the amino acid phenylalanine to tyrosine. As a result, phenylalanine accumulates in the body, leading to elevated levels in the blood and urine. If untreated, PKU can result in intellectual disability, developmental delays, and other neurological problems. Treatment typically involves dietary restrictions to limit phenylalanine intake.

2.     Tyrosinemia: Tyrosinemia refers to a group of genetic disorders characterized by the accumulation of tyrosine and its metabolites in the body. There are several types of tyrosinemia which leads to the accumulation of toxic metabolites and can result in liver and kidney damage if left untreated.

3.     Alkaptonuria: In alkaptonuria, the missing enzyme is called homogentisate 1,2-dioxygenase. This enzyme is responsible for breaking down homogentisic acid, but its deficiency leads to the accumulation of homogentisic acid in the body. In alkaptonuria, symptoms can include darkening of urine when it's exposed to air, joint problems, and sometimes other health issues.

PLASMA PROTEINS:

Plasma proteins are essential components of blood that serve various functions crucial for maintaining homeostasis and overall health. These proteins are synthesized primarily in the liver and circulate in the bloodstream. The main types of plasma proteins include albumin, globulins, and fibrinogen.

1.     Albumin:

·         Function: Retains water inside blood vessels, maintains osmotic pressure.

·         Normal value: Approximately 3.5 to 5.0 grams per deciliter (g/dL).

2.     Globulins:

·         There are three types: alpha, beta, and gamma.

·         Alpha and beta globulins primarily transport lipids and metal ions.

·         Gamma globulins: Also known as immunoglobulins or antibodies, these globulins play a crucial role in the immune system by recognizing and neutralizing pathogens such as bacteria and viruses.

·         Normal values:

·         Alpha globulins: Typically around 0.1 to 0.3 g/dL.

·         Beta globulins: Usually fall within the range of 0.6 to 1.0 g/dL.

·         Gamma globulins: Typically ranges from 0.7 to 1.6 g/dL.

3.     Fibrinogen:

·         Function: Plays a crucial role in blood clotting by converting to fibrin, which forms a mesh-like structure to stop bleeding.

·         Normal range: Approximately 200 to 400 milligrams per deciliter (mg/dL).

MEDICAL CONDITIONS RELATED TO ABNORMALITIES IN PROTEIN LEVELS IN THE BODY:

PROTEINURIA:

Proteinuria is a medical condition characterized by the presence of an abnormal amount of protein in the urine. Causes of proteinuria can vary and may include:

1.     Kidney disease or damage: Conditions such as glomerulonephritis, diabetic nephropathy, hypertensive nephrosclerosis, and certain inherited kidney disorders can lead to proteinuria by affecting the filtration function of the kidneys.

2.     Hypertension (high blood pressure): Chronic hypertension can cause damage to the tiny blood vessels in the kidneys, impairing their ability to filter waste products and leading to proteinuria.

HYPOPROTEINEMIA:

Hypoproteinemia is a medical condition characterized by abnormally low levels of protein in the blood, particularly low levels of albumin and/or globulins. Hypoproteinemia can result from a variety of factors, including:

1.     Malnutrition: Inadequate intake of protein in the diet can lead to hypoproteinemia. Malnutrition, particularly protein-energy malnutrition, can occur due to insufficient dietary protein intake.

2.     Liver disease: The liver plays a crucial role in protein metabolism, including the synthesis of albumin and other plasma proteins. Liver diseases such as cirrhosis, hepatitis, and liver failure can impair the liver's ability to produce an adequate amount of proteins, leading to hypoproteinemia.

3.     Kidney disease: The kidneys are responsible for filtering waste products and excess substances from the blood, including proteins. In conditions such as nephrotic syndrome, glomerulonephritis, and diabetic nephropathy, the kidneys may become damaged, allowing proteins, particularly albumin, to leak into the urine, leading to hypoproteinemia.

4.     Gastrointestinal (GI) disorders: Disorders affecting the gastrointestinal tract can impair the absorption of nutrients, including proteins, resulting in hypoproteinemia.

HYPER GAMMA GLOBINEMIA:

Hypergammaglobulinemia is a medical condition characterized by elevated levels of gamma globulins, particularly immunoglobulins (antibodies), in the blood. Immunoglobulins are proteins produced by the immune system in response to the presence of foreign substances (antigens) such as bacteria, viruses, or other pathogens.

Causes of hypergammaglobulinemia may include:

1.     Chronic infections: Persistent or chronic infections, such as viral infections (e.g., hepatitis, HIV), bacterial infections (e.g., tuberculosis), parasitic infections, or fungal infections, can stimulate the immune system to produce increased amounts of antibodies, leading to hypergammaglobulinemia.

2.     Autoimmune disorders: Autoimmune diseases occur when the immune system mistakenly attacks the body's own tissues, leading to inflammation and tissue damage.

ELECTROPHORESIS:

Electrophoresis is a laboratory technique used to separate and analyze charged particles, such as proteins, nucleic acids, and other macromolecules, based on their size, shape, and charge.

Basic principle of electrophoresis:

1.     Electric field: Electrophoresis requires the application of an electric field across a medium in which the charged particles will migrate. Typically, this is achieved by placing the sample in a buffer solution and applying an electrical potential across the buffer using electrodes. The electric field exerts a force on the charged particles, causing them to move through the medium.

2.     Supporting medium: The sample containing the charged particles is loaded onto a supporting medium, often made of agarose gel or polyacrylamide gel. These gels act as sieves, allowing the separation of molecules based on their size and charge.

3.     Migration: Once the electric field is applied, charged particles within the sample migrate through the supporting medium at different rates based on their size and charge. Smaller, more highly charged particles move faster through the gel matrix, while larger, less charged particles move more slowly. This differential migration leads to the separation of the particles into distinct bands or zones along the gel.

4.     Visualization and analysis: After electrophoresis, the separated particles are visualized using staining techniques or fluorescent markers specific to the type of molecule being analyzed. The distance traveled by each band or zone can be measured and correlated with the size or charge of the particles.