Protein Structure and Function - Group 5 PDF

PROTEIN STRUCTURE AND FUNCTION BY GROUP 5 MEMBERS DEC 2025  OBJECTIVES  Definition of proteins  Fundamental unit of a protein  Categorization of amino acids  Levels of protein structure in the body with relevant examples  Physiological relevancy of proteins in t...

PROTEIN STRUCTURE AND FUNCTION BY GROUP 5 MEMBERS DEC 2025  OBJECTIVES  Definition of proteins  Fundamental unit of a protein  Categorization of amino acids  Levels of protein structure in the body with relevant examples  Physiological relevancy of proteins in the body  Clinical correlates associated with excess and low proteins in the body  Digestion and absorption of proteins in the body  Enzymology  Chemical nature and properties  Mechanism of enzyme action  Enzyme inhibition  Classification  Factors affecting enzyme activity  Application of enzymes and clinical correlates  Definition of Proteins  Proteins are large, complex molecules composed of amino acids linked by peptide bonds.  They are essential for the structure, function, and regulation of the body's tissues and organs.  The sequence and arrangement of amino acids in a protein determines its specific function and shape which is vital for its activity in the body. The Fundamental Unit of a Protein  The fundamental unit of a protein is the amino acid (a.a)  A.A are organic compounds containing an amino group (-NH2) and a carboxyl group (-COOH).  Amino acids overview  20 amino acids are of biological importance.  Also referred to as the standard or primary or normal amino acids.  All are exclusively of the L-configuration (Levorotatory)  L-configuration determines their stereochemistry  They all have a hydrogen atom (-H), a carboxyl group (- COOH) and an amino group (-NH2) bound to the same carbon atom  The carbon atom is called the α-carbon  The α-carbon is a chiral carbon for all a.a except for glycine (-R = H)  Amino acids differ from each other in their side chains or R-groups, attached to the α-carbon.  The R-group determines the specific properties of the a.a  How the protein molecule is formed  2 amino acids link up to form a protein molecule through a peptide bond.  The amino group of one a.a reacts with the carboxyl group of another a.a and a water molecule is released. This is known as a condensation reaction.  The resulting bond formed is the peptide bond between the carbon atom of the carboxyl group of one a.a and the nitrogen atom of the amino group of another a.a  When another a.a is added, the bond formed is referred to as a dipeptide bond.  When numerous a.a are bonded together the resultant protein is said to have polypeptide bonds. Formation of a peptide bond  Categorization of a.a Can be grouped into 5 basing on their properties; 1. Chemical nature of the amino acid in the solution  Neutral vs acidic vs basic 2. Structure of the side chain of the amino acids  Aliphatic, Hydroxy, Sulfur containing, Dicarboxylic acid and their amides, Diamino acids, Aromatic amino acids, Imino acids or heterocyclic amino acids 3. Nutritional requirement of amino acids  Essential vs Non-Essential 4. Metabolic product of amino acids  Glucogenic vs ketogenic vs both 5. Nature or polarity of the side chain of the amino acids.  Hydrophilic vs hydrophobic  Structure of the side chain of the amino acids  Hydroxy,  Sulfur containing,  Dicarboxylic acid and their amides,  Diamino acids,  Aromatic amino acids,  Imino acids heterocyclic amino acids Structure of side chain cont…. Structure of side chain cont….  Chemical nature of the amino acid in solution  Neutral amino acids: The amino acids which are neutral in solution  are monoamine-monocarboxylic acids (i.e. having one amino group and one carboxylic group)  Glycine, Serine, Phenylalanine, Alanine, Threonine, Tyrosine, Valine, Cysteine, Tryptophan, Leucine, Methionine, Asparagine, Isoleucine, Proline, Glutamine  Acidic amino acid  are acidic in solution and are monoamino-dicarboxylic acids  Aspartic acid  Glutamic acid  Basic amino acid; These are basic in solution and are diamino- monocarboxylic acids  Lysine  Arginine  Histidine Nutritional requirement of amino acids  Essential amino acids  Cannot be synthesized in our body therefore must be essentially supplied in the diet.  Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine, Lysine, Leucine.  Non-essential amino acids  can be synthesized in our body, so, not required in diet  Alanine, Aspartic acid, Cysteine, Glutamic acid, Glycine, Proline, Serine, Asparagine, Glutamine, Tyrosine  Semi essential amino acids  partially synthesized  Histidine, Arginine  Classification basing on metabolic end product of the amino acids On the basis of their metabolic fate a.a are divided into;  Both glucogenic and ketogenic a.a (4):  Can be converted to both glucose and ketone bodies.  isoleucine, phenylalanine, tryptophan and tyrosine are glucogenic and ketogenic.  Purely Ketogenic amino acids (2):  Can be converted to ketone bodies.  leucine and lysine  Purely Glucogenic amino acids (14):  Can be converted into glucose  Include all the rest of the a.a Nature or polarity of the side chain of the amino acids  Levels of Protein Structure with Examples  Proteins have four levels of structure: 1. Primary: Linear sequence of amino acids. Proteins have unique amino acid sequences and are specified by genes.  Amino acids in the primary structure are linked by peptide bonds.  Linkage of many a.a through peptide bonds results in an unbranched chain called a polypeptide.  Each amino acid in a polypeptide is called a residue or moiety.  Each polypeptide chain is having free amino group at one end called N terminal and free carboxyl group at another end, called C-terminal.  Examples include; Insulin, Ribonuclease Schematic representation of the primary structure of protein  Secondary structure  This is localized folding of the polypeptide chain into specific shapes, primarily established by hydrogen bonds between the backbone atoms.  Secondary structure is composed of;  Alpha helix  A helix is a rod-like structure. Alpha because it was the first of the 2 secondary structures to be discovered.  It consists of a backbone of a polypeptide chain twisted by equal amounts about each α-carbon.  This results in a right-handed coil where each turn consists of about 3-4 amino acids  The helix is stabilized by hydrogen bonds and these are between NH and CO groups in the same polypeptide chain.  Example of this is keratin which is present in hair, skin, nails. Schematic diagram of α-helical structure of protein  Beta pleated sheets  Beta pleated sheets(zig-zag folding)  Formed by linking two or more strand of a.a lying next to each other through hydrogen bonds which can be parallel or anti-parallel The surfaces of β-sheet appear “pleated” hence their name  Unlike α-helix, β-pleated sheets are composed of two or more polypeptide chains.  β-pleated sheet is stabilized by hydrogen bonds between NH and C=O groups in a different polypeptide chain  Altered folding leads to formation of amyloid proteins  Examples of proteins in the form of Beta sheets include Collagen and antibodies, β-Keratins present in spider’s web, reptilian claw, fibers of silk. Illustration of the beta pleated sheet  Tertiary structure  The polypeptide chain with secondary structure may be further folded, superfolded twisted about itself forming many sizes.  This creates an overall 3-dimensional shape of a single polypeptide chain formed by interactions among various side chains (-R groups) of a.a.  The interactions include;  Hydrogen bonds  Ionic bonds  Hydrophilic interactions  Disulfide bridges van der Waal’s forces  Covalent bonds between cysteine residues  E.g myoglobin Tertiary structure of a protein  Quaternary structure  This structure only applies to proteins that have more than one polypeptide chain (polymeric) as opposed to monomeric  The arrangement of these polymeric polypeptide subunits in three- dimensional complexes is called the quaternary structure of the protein  These polypeptide subunits are held together by non-covalent interactions or by covalent cross-links.  The assembly is often called an oligomer and each constituent peptide chain is called as monomer or subunit. The monomers of oligomeric protein can be identical or different in primary, secondary or tertiary structure.  Examples:  Protein with two monomers (dimer)  Enzyme creatine phosphokinase (CPK).  Protein consisting of four monomers Tertramers  Haemoglobin  lactate dehydrogenase (LDH).  Apoferritin contains 24 identical subunits.  Many proteins function as complexes of multiple subunits. Disruption in the interaction between subunits affects functionality. E.g Hemoglobin’s ability to transport oxygen relies on the proper assembly of its four subunits, mutations affecting this assembly can lead to disorders like thalassemias. Schematic representation of quaternary structure of polymeric protein  Alterations in protein structure and their  consequences Primary structure  Point mutations; this is a single change in sequence of amino acids e.g. in sickle cell anemia, caused by a single nucleotide mutation in the hemoglobin gene.  Insertions/deletions: result in completely different amino acids sequence producing non functional proteins e.g. in cystic fibrosis  Secondary structure  Changes in hydrogen bonding patterns can disrupt alpha helices and beta sheets e.g. misfolded proteins in Alzheimer's disease often involve aberrant beta sheet formation leading to amyloid plaque.  Tertiary structure  Denaturation or loss of shape can render enzymes inactive for example due to high temperature  Misfolding can also occur leading to cystic fibrosis.  Quaternary structure  Disruption in the interaction between subunits of the quaternary structure can affect functionality of a protein for example mutations affecting assembly of hemoglobin subunits can lead to disorders such as Thalassemia  Physiological Relevance of Proteins Proteins perform various functions:  Structural role  Collagen in connective tissues, provides strength and elasticity in skin, bones and tendons  Keratin forms hair, nails, outer layer of the skin  Actin and myosin for muscle contraction  Transport and storage  Transporting molecules across membranes and within the blood stream  Transport oxygen in blood (Hb)  Albumin transports hormones and drugs  Ferritin stores iron in cells  Physiological relevance continued….  Enzymatic function  Speeding up chemical reactions e.g hexokinase, ALT, AST, DNA polymerase  Immune function:  Antibodies (Immunoglobulins) defend against pathogens by recognizing and neutralizing them  Complement proteins – play an important role in enhancing the ability of antibodies and phagocytic cells to recognize and eliminate pathogens. Thes proteins are activated in a cascade manner.  Hormonal regulation  Protein hormones such as insulin and glucagon which regulate blood glucose levels  Adrenocorticotropic hormone which regulate the adrenal gland  Physiological relevance continued…  Fluid balance  This is achieved by the plasma proteins albumins which regulate the plasma oncotic pressure.  PH balance  Achieved by Hemoglobin and albumin which act as plasma protein buffers and prevent changes in PH in blood.  Movement  Achieved by myosin and actin which are contractile proteins found in muscle tissue.  Energy source  When carbohydrates and fats are scarce, proteins are broken down to provide energy via gluconeogenesis.  Digestion and Absorption of Proteins  Protein digestion: Begins in the stomach  Proteins are denatured by HCl produced by parietal cells of the stomach  HCl also activates pepsin in the stomach  Pepsin breaks downs proteins into smaller polypeptides  In the small intestines  Pancreatic enzymes in small intestines trypsin, chymotrypsin, carboxypeptidases)break down small polypeptides into smaller peptides and a.a  Other enzymes in small intestinal (aminopeptidases, dipeptidases) break down the smaller polypeptides into single a.a, dipeptides and tripeptides.  Digestion and absorption of proteins contd…..  Absorption in the small intestines  Transport across the enterocytes (intestinal cells) via specialized transporters  Involves active transport  Inside enterocytes  Di and tri peptides are further hydrolyzed into free a.a by intracellular enzymes. Digestion of proteins continued… Digestion of proteins continued… Digestion of proteins continued… Absorption of amino acids Absorption of amino acids continued… Abnormalities of protein digestion and absorption Clinical Correlates of Protein Imbalance  Excess proteins:  An abnormally high level of proteins in the body, leading to;  Dehydration due to decrease in plasma volume  Chronic inflammation and chronic infection  Multiple myeloma  A type of cancer where plasma cells produce excess Immunoglobulins  Macroglobulinemia  The body produces too much of a particular IgM  Amyloidosis  Low protein  Abnormally low proteins in the body  Caused by  Liver disease  Acute or chronic blood loss  Increased protein loss  Nutrition deficiency  Malabsorption syndrome  Effects on the body  Causes muscle wasting  Edema  Weakened immunity  Nephrotic syndrome  Bleeding tendencies  Malnutrition (PEM) Clinical Correlates of Protein Imbalance… pictorial  References  Chatterjee MN, Rana Shinde, Textbook of Medical biochemistry 8th Edition  Pakanja Naik, Essentials of Biochemistry, First Edition, 2012.  Lehninger Principles of Biochemistry, 4th edition