Biochemistry - Proteins PDF

BIOCHEMISTRY  The simplest amino acid is glycine, where R=H PROTEIN Characteristics of Proteins  A protein is naturally-occurisng, unbranched polymer in which the mon...

BIOCHEMISTRY  The simplest amino acid is glycine, where R=H PROTEIN Characteristics of Proteins  A protein is naturally-occurisng, unbranched polymer in which the monomer units are amino acids  Proteins are most abundant molecules in the cells after water-account for about 15% of a sales over all mass  The R group, called the side chain, determines the identity of the amino acid  Elemental composition contain Carbon C) Hydrogen(H), Nitrogen (N), Oxygen (O)  If R = a basic N atom, it is a basic amino and Sulfur (S) acid  The average nitrogen content of proteins  If R = an additional COOH group, it is an is 15.4% by mass acidic amino acid  Also present are Iron (Fe), pHosphorus (P)  Amino acod - An organic compound that and some other metals in some contains both an amino (-NH2) and are specialized protein carboxyl (-COOH) group attached to same carbon atom  Proteins account for 50% of the dry weight of the human body - The position of carbon atom is alpha (a)  They have many functions in the body - -NH2 group is attached at alpha (a) carbon atom  Current recommended daily intake for adult is 0.8 g of protein per kg of body - -COOH group is attached at alpha (a) weight (more is needed for children) carbon atom  Dietary proteins comes for eating meat - R = side cahian -- vary in size, shape, and milk charge, acidity, functional groups present, hydrogen-bonding ability, and chemical  Proteins are biomelecules that contain reactivity many amide bonds formed by joining amino acid - >700 amino acids are known - Based on common 'R' groups, there are 20 standard amino acid Amino ACIDS: The Building Blocks for Proreins  All amino acids differ from one  Amino acids contain two functional another by their R-groups groups an amino group (NH2) and the carboxyl group (COOH) - Their are 20 common (standard) amino acids  The amino group is attached to the a- carbon the C atom adjacent to the  Standard amino acids are divided into carbonyl group four group based on the properties of R- group.  Non-polar amino acids: R-groups are non- polar - Such amino acids are hydrophobic water fearing (insoluble water) -8 of the 20 standard amino acids are nonpolar  - when present in proteins, they are located in the interior of protein where there is no polarity  Polar amino acids: R-groups are polar - Three types: Polar neutral; Polar acidic; and Polar basic  Polar-neutral: contains polar but Essential Amino Acids neutral side chains  Essential Amino Acids: A standard amino - Two amino acids belong to this acid needed for protein synthesis that category must be obtained from dietary sources - adequate amount s cannot be  Polar-basic: Contain amino group as synthesized in human body. part of the side chain  Nine of the 20 standard amino acids are - Two amino acids belong to this considered essential category *Required for Nomenclature growth in children and is not essential for  Common names assigned to the amino adults acids are currently used  Three letter- abbreviations widely used for naming: Chirality and Amino Acids - First letter of amino acid name is compulsory and capitalized followed by  Four different groups are attached to the next two letters not capitalized except in a-carbon atom in all of the standard the case of Asparagin (Asn), Glutamine amino acid except glycine (Gln) and Tryptophan (Trp) - In glycine R-group is hydrogen  One-letter symbols- commonly used for comparing amino acid sequences of  Therefore 19 of the 20 standard amino proteins: acids contains chiral center - Usually the first letter of the name  Molecules with gerald center exhibit inantiomerism (left-and right-handed - When more than one amino acid has the forms) same letter the most abundant amino acid gets the first letter  The amino acids found in nature as well as in proteins are L isomers  Both types of abbreviation are given: - bacteria do have some D-amino acids - With monosaccharides nature favors D- isomers  The rules for drawing Fischer projection formulas for amino acid structures - The -- COOH group is put at the top - The R group is placed at the bottom position of the carbon chain vertically - The NH2 group is placed in horizontal position - Positioning -- NH2 on the left - L isomers - Positioning -- NH2 on the right - D isomer   When the pH>isoelectric pH, the ammonium cation loses a proton, and Designed the amino acid has a net negative mirror charge handedness in standard amino acid structure s Peptides  All amino acids (save glycine) have a Nature of Peptide Bond chirality center on the a-carbon  Under proper conditions, amino acids can bond together to produce an unbranched chain of amino acids - The reactions is between amino group of one amino acid and carboxyl group of another amino acid  The length of the amino acid chain can vary from a few amino acids hundreds of amino acids  L amino acid have the -NH3+ group on the  Such a chain of covalently-linked amino left acids is called a peptide  D amino acids have the -NH3+ group on  The covalent bonds between amino acids the right in a peptide are called peptide bonds (amide) Acid-Base Properties of Amino Acids  Since amino acids contain a base (NH2) and an acid (COOH), a proton transfers from the acid to the base to form a zwitterion  Peptides and protein s are formed when amino acids are joined together by amide bonds  A dipeptide has two amino acids joined together by one amide band  An amino acid exist as a neutrally charged zwitterion at a certain pH, the isoelectric pH  The amino acid can exist in different forms depending on the ph of the aqueous environment  The am i bad is called a peptide bond  When the pH10,000 amino acid residues are known  All bond angles are 120o, giving the protein a zigzag arrangement -Common proteins contain 40-100 amino acid residues  More than one polypeptide chain may be present in a proteins: - Monomeric: Contains one polypeptide chain - Multimeric: Contains 2 or more polypeptide Primary Structure of a Human Myoglobin Protein Classification Based on Chemical Composition  Simple proteins: A protein in which only amino acid residues are present: -More than one protein subunit may be present but all subunits contain  Proteins of the same organism always only amino acids same sequence.  Conjudge (complex) proteins: A  Same protein from different sources; proteins that has one or more non- eg., INsulin from pigs, cows, sheep, amino acid entities (prosthetic groups) human, are similar but not identical present in its structure  Due to the differences, insulin may - One or more polypeptide chains may show some difference in response be present overtime - Non-amino acid components- may  Now human insulin produced from be organic or inorganic-prostehtic genetically engineered bacteria groups -Lipoproteins contain lipid prosthetic groups 2. Secondary Structure -Glycoproteins contain carbohydrate  Arrangement of atoms of backbone in groups space. -Mettaloproteins contain a specific  The two most common types : alpha- metal as prosthetic group helix (a-helix) and the beta-pleated sheet (b-pleated sheet)  The peptide linkages are essentially Primary Structure of Proteins planar thus allows only two possible arrangement for the peptide Four Types of Structure backbone for the following reasons: 1. Primary Structure - For two amino acids linked through a peptide bond six atoms lie in the  same plane  Most proteins have regions of a-helix and B-pleated sheet, and other - The planar peptide linkage structure regions that are random has considerable rigidity, therefore arrangements rotation of groups about the C-N bond is hindered - Cis-trans isomerism is possible about C-N bond - The trans isomer is the prefers orientation Alpha-helix (a-helix)  A single protein chain adopts a shape that resembles a coiled spring (helix): - H-bonding between amino acids with in the same chain-intramolecular H-bonding - Coiled helical spring - R-groupsstay outside of the helix-- not enough room for them to stay inside 3. Tertiary Structure  The overall three-dimensional shape of a protein  Results from the intersections between amino acid side chains (R groups) that are widely separated from each other. Beta-Pleated Sheets  In general 4 types of interactions are  Completely extended amino acid observed. chains - Disulfide bonding  H-bonding between two different chains- inter and/ or intramolecular - Electrostatic interactions  Side chains below or above the axis - H-bonding - Hydrophobic interactions Four Types of Interactions  Disulfide bond: covalent, strong, between two cysteine groups  Electrostatic interactions: Salt bridge between charged chains of acidic and  The secondary structure is the 3D basic amino acids arrangement of localized regions of a protein - -OH, -NH2, -COOH, -CONH2  H-bonding between polar, acidic and/or  These regions arise due to hydrogen basic R groups bonding between the N-H group of one amide with the C=O group of -For H-bonding to occur, the H must be another attached to O, N or F  Two stable arrangement are the a-  Hydrophobic interactions: Between helix and the B-pleated sheet  non-polar side chains Protein Hydrolysis  Hydrolysis of proteins - reverse of peptide bond formation: - Result in the generation of an amine and a carboxylic acid functional groups. - Digestion of ingested protein is enzyme- catalyzed hydrolysis - Free amino acids produced are absorbed into the bloodstream and transported to the liver for the systhesis of new proteins - Hydrolysis of cellular proteins and their resynthesis is a continuous process 4. Quaternary Structure  Quaternary structure of protein refers to the organization among the various polypeptide chains in a multimeric protein: -----------  Highest level of protein organization  Present only in proteins that have 2 or more polypeptide chains (subunits)  Subunits are generally independent of each other not covalently bonded  Proteins with quaternary structure are often referred to as oligomeric proteins Protein Denatuartion  Contain even number of subunits  Partial or complete disorganization of protein's tertiary structure  Cooking food denatures the protein but does not change protein nutritional value  Coagulation: Precipitation (denaturation of proteins) -Egg white - a concentrated solution of protein albumin - form a jelly when heated because the albunim is denatured  Cooking: - Denatures proteins - Make it easy for enzymes in our body to hydrolyze/digest protein -Kills microorganisms by denaturation of proteins - Fever: >104oF - the critical enzymes of the body start getting denatured -End  Protein Classification Based on Shape  Hardness of keratin depends upon -S-S- bonds  Three types of proteins: fibrous, globular, and membrane -More -S-S- bonds make nail and bones hard and hair brittle  Fibrous proteins: protein molecules with elongated shape: - Generally insoluble in water Common Proteins a-Keratins - Single type of secondary structure - Tend to have simple, regular, linear structures - Tend to aggregate together to form macromolecular structures, e.g., hair, nails, etc Collagen's  Globular proteins: protein molecules with Triple Helix peptide chains folded into spherical or globular shapes: - Generally water soluble - hydrophobic amino acid residues are in the protein core Fibrous Proteins: Collagen - Function as enzymes and intercellular  Most abundant proteins in human (30% of signaling molecules total body protein)  Membrane proteins: associated with cell  Major structural material in tendonds, membranes legaments, blood vessels, and skin -Insoluble in water - hydrophobic amino  Organic component of bones and teeth acid residues on the surface  Predominant structure - triple helix - Help in transport of molecules across the  Rich in proline ( up to 20%) - important to membrane maintain structure Fibrous Proteins Globular Proteins  Fibrous Proteins: contain polypeptide  Globular proteins: proteins which are chains organized approximately parallel folded to a more or less spherical shape along a single axis. They - consist of long fibers or large sheets - they tend to be soluble in water and salt solutions - tend to be mechanically strong - most of their polar side chains are on the - are insoluble in water and dilute salt outside and interact with the aqueous solutions environment by hydrogen bonding and ion-dipole interactions - play important structural roles in nature -most of their nonpolar side chains are  Example are buried inside  Keratin of hair and wool -nearly al have substantial sections of a- helix and B-sheet  Collagen of connective tissue of animals including cartilage, bone, teeth, skin, and blood vessels Fibrous Proteins: Alpha-Keratin  Provide protective coating for organs  Major proteins constituent of hair, feather, nails, horns and turtle shells  Mainly made of hydrophobic amino acid residues Globular Proteins : Myoglobin  Globular Proteins: Myoglobin - An oxygen storage molecule in muscles - Monomer - single peptide chain with one heme unit - Binds one O2 molecule -Has a higher affinity for oxygen than Hemoglobin is a tetrameter, consisting of hemoglobin four polypeptide chains, wo a-chains, and two B-chains -Oxygen stored in myoglobin molecules serves as a reserve oxygen source for  Carbon monoxide (CO) is poisonous working muscles because it binds 200 times more strongly to the Fe+2 than does O2  Hemoglobin complexed with CO cannot carry O2, and cells will die from lack of O2  Sickle cell anemia is a disease The Structure of where a single amino acids is different in Myoglobin two of the subunits of hemoglobin -has 153 Amino  Red blood cells containing these acids mutated hemoglobin units become elongated and crescent (sickle) shaped  These red blood cells will rupture capillaries, causing pain and inflammation, leading to organ damage, and eventually a painful death  Proteins play crucial roles in most biochemical  The diversity of functions exhibited by proteins far exceeds the roles of other biochemical molecules Oxygen  The functional versatility of proteins Binding Site stems from: of Myoglobin - Ability to bind small molecules specifically and strongly - Ability to bind other proteins and form fiber-like structure, and - ability integrated into cell membranes Major Categories of Proteins Based on Function Globular Proteins: Hemoglobin  Catlytic proteins: Enzymes are best known for their catalytic role.  An oxygen carrier molecule in blood -Almost every chemical reaction in the  Transports oxygen from lungs to tissues body is driven by an enzymes  Tetrameter (four polypeptide chains) -  Defense proteins: Immunoglobulins or each subunit has a heme group antibodies are central to functioning of the body's immune system  Can transport up to 4 oxygen molecules at time  Transport proteins: Bind small biomolecules, e.g., oxygen and other  Iron atom in heme interacts with oxygen ligands, and transport them to other locations in the body and release them on  demand. Glycoproteins  Messenger proteins: transmit signals to  Conjugated proteins with coordinate biochemical processes carbohydrates linked to them: between different cells, tissues, and organs. - many of plasma membrane proteins are glycoproteins - Insulun and glucagon - regulate carbohydrate metabolism - blood group markers of the ABO system are also glycoproteins - Human worth hormone regulate body growth - collagen and immunoglobulins are glycoproteins  Contractile proteins: Necessary for all forms of movements.  Collagen -- glycoproteins -Muscle contain filament-like contractile - most abundant proteins in human body proteins (actin ad myosin). (30% of total body protein) - Human reproduction depends on the - triple helix structure movement of sperm possible because of contractile proteins - rich in 4-hydroxyproline (5%) and 5- hyroxylysine (1%) - derivatives  Structural proteins: Confer stiffness and rigidity - some hydroxylysines are linked to glucose, galactose, and their - collagen is a component of cartilage disaccharides - help in aggregation of collagen fibrils. - Keratin gives mechanical strength as well as protective covering to hair, Immunoglobulins fingernails, feathers, hooves, etc.  Glycoproteins produced as a protective  Transmembrane proteins; Span a cell response to the invasion of membrane and help control the microorganisms are foreign molecules- movement of small molecules and ions antibodies against antigens - Have channels - help molecules to enter  Immunoglobulin bonding to an antigen and exist the cell via variable region of an immunoglobulin occurs through hydrophobic interactions, - Transport is very selective - allow dipole- dipole interactions, and hydrogen passage of one type molecule or ion. bonds.  Storage proteins: bind (and store) small molecules - Ferritin - an iron- storage protein- saves iron for use in the biosynthesis of new hemoglobin molecules. -Myoglobin - an oxygen- storage protein present In muscle  Regulatory proteins: Often found Lipoproteins “embedded” in the exterior surface of cell membranes - act as sites for receptors  Lipoproteins: a conjugated protein that molecules contains lipids in addition to amino acids. - Often the molecules that bind to  Major function- help suspend lipids and enzymes (catalytic proteins), thereby transport them through the bloodstream. turning them ''on'' and ''off'' and thus controlling enzymatic action  Four major classes of plasma lipoproteins:  Nutrient proteins: Particularly important - Chylomicrons: Transport dietary in the early stages of life- from embryo to triaclyglycerols from intestine to liver and infant to adipose tissue - Casein (milk) and ovalalbumin (egg - Very-low-density lipoproteins (VLDL): white) are nutrient proteins transport triaclyglycerols synthesized in the liver to adipose tissue - milk also provide immunological protection for mammalian young - low-density lipoproteins (LDL): transport cholesterol synthesized in the liver to cells throughout the body. - High - density lipoproteins (HDL): collect excess cholesterol from body tissues and transport it back to the liver for dega