The word protein comes from the Greek proteios, which means of first importance.

 The name was proposed in year 1840 by Mulder, a Dutch chemist.

What is PROTEIN?
 It is a naturally occurring, unbranched polymer in which the monomer units are amino acids.

 A large complex organic compounds composed of amino acids as the building units linked together in peptide bonds.

CHARACTERISTICS

1. 2.

Next to water in the most abundant substances in nearly all cells.

15% - cells overall mass (typical human cell contains about 9,000 different kind of proteins) Almost half of the cells dry mass (human body contains about 100,000 different proteins)

Presence of nitrogen
15.4% by mass (average nitrogen content of proteins)

Other elements such as phosphorus and iron are essential constituents of certain specialized proteins.
Casein- main protein of milk, contains phosphorus Hemoglobin- oxygen- transporting protein contains iron.

1. 2.

Classification based on FUNCTIONS

 Catalytic Proteins- virtually all the reactions that take place in living organisms are catalyzed by proteins called enzymes.  Defense Proteins- are also called immunoglobulin or antibodies, are central to the functioning of the bodys immune system.  Transport Proteins- these proteins bind to particular small biomolecules and transport them to other locations in the body and then release the small molecules as needed at the destination location, e.g., hemoglobin, transferrin, high and low density lypoproteins.  Messenger Proteins- transmit signals to coordinate biochemical processes between different cells, tissues and organs. E.g., insulin, glucagon and human growth hormone.  Contractile Proteins- necessary for all forms of movement, e.g., actin and myosin.

 Structural Proteins- confers stiffness and rigidity to otherwise fluid-like biochemical systems. E.g., collagen

 Transmembrane Proteins- help control the movement of small molecules and ions through the cell membrane.  Storage Proteins- bind and store small molecules for future use, e.g., ferritin, myoglobin

 Regulatory Proteins- control the expression of genes, and thereby regulate the kind of proteins manufactured in a particular cell and control when such manufacture takes place.

 Nutrient Proteins- important in the early stages of life from embryo to infant. E.g., casein, and ovalbumin

What is an AMINO ACID?

an organic compound that contains both an amino group and carboxyl group.  - amino acid- always found in proteins, an amino acid in which the amino
group and the carboxyl group are attached to the - carbon atom.

GENERAL STRUCTURAL FORMULA

STANDARD AMINO ACID

- one of the 20 - amino acids normally found in proteins.

GROUP according to SIDE- CHAIN POLARITY

Non polar amino acid- contains one amino group, one carboxyl group and a
non polar side- chain, when incorporated into a protein they are hydrophobic generally found in the interior of proteins. - Glycine , Alanine , Valine , Leucine , Isoleucine , Proline , Phenylalanine , Methionine , & Trytophan

POLAR NEUTRAL AMINO ACID - contains one amino group, one carboxyl group and a side- chain that is polar but neutral. - Serine , Cysteine , Threonine , Asparagine , Glutamine , Tyrosine

POLAR ACIDIC AMINO ACID

contains one amino group and two carboxyl groups, the second carboxyl groups being part of the side- chain. Aspartic acid & Glutamic acid

POLAR BASIC AMINO ACID

contains two amino groups and one carboxyl group, the second amino group being part of the side-chain. Histidine , Lysine , Arginine

CLASSIFICATION OF AMINO ACID Based on Chemical Components

8 Essential (indispensable) Isoleucine ( Ile ) Leucine (Leu) Lysine (Lys) Methionine (Met) Phenylalanine (Phe) Threonine (Thr) Tryptophan (Trp) Valine (Val) 6 semi- essential (semi- dispensable) Arginine (Arg ) Histidine ( His ) Tyrosine ( Try ) Cystine (Cys ) Glycine ( Gly ) Serine ( Ser ) 9 nonessential (dispensable) Glutamic Acid ( Glu ) Hydroxygutamic Acid Aspartic Acid ( Asp ) Alanine ( Ala ) Proline ( Pro ) Hydroxyproline Norleucine Citrulline Hydroxyglycine

CHIRALITY
Four different groups are attached to the - carbon in all of the standard amino acids (except glycine, where the R group is a hydrogen atom)

* Glycine- the simplest of the standard amino acids is achiral.

ACID- BASE PROPERTIES OF AMINO ACIDS

 In pure form, amino acids are white crystalline solids with relatively high decomposition points (most amino acids decompose before they melt)

Most acids are not very soluble in water

Amino acids are charged species both in the solid state and in solution

 Both an acidic group (-COOH) and a basic group (-NH2 ) are present in the same carbon in an - amino acid.

ZWITTERIONS
Compounds that has a positive charge on one atom and a negative charge on another, but which has no net charge. Comes from the German zwitter, meaning double ion. The net charge on a zwitterion is zero even though parts of the molecule carry charges in solution and also in the solid state - amino acids exists as zwitterions. In an acidic solution, the zwitterion accepts a proton (H+) to form a positively charge ion. In basic solution, NH3 of the zwitterion loses a proton, and a negatively charge species is formed.

ISOELECTRIC POINTS
NAME ISOELECTRIC POINT 6.01 10.76 5.41 2.77 5.07 3.22 5.65 5.97 7.59 6.02 5.98 9.74 5.74 5.48 6.48 5.68 5.87 5.88 5.66 5.97

The pH at which an amino acid solution has no net charge because an equal number of positive and negative charges are present, every amino acid has a different isoelectric points. ELECTROPHORESIS the process of separating charged molecules on the bases of their migration toward charged electrodes associated with an electric field.

Alanine Arginine Asparagine Aspartic acid Cysteine Glutamic acid Glutamine Glycine Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Prolein Serine Threonine Trytophan Tyrosine Valine

Predicting the direction of migration

EXAMPLE:
Serine at pH= 1.0 and 5.68 Answers: At pH= 1.0 ( migration towards negatively charged electrode ) At pH= 5.68 (ISOELECTRIC )

CYSTEINE: a special amino acid

 The only standard amino acid that has a side- chain that contains sulfhydryl group ( -SH group).

 Cysteine, in the presence of mild oxidizing agents readily dimerizes, that is, reacts with anothes cysteine molecule to form cystine molecule. ( a dimer is a molecule that is made up of two like subunits)  The presence of cysteine has important consequences for the chemical structure and shape of protein molecules it is a part of.  The S-S bond is called a disulfide linkage.

PEPTIDES and PROTEINS

PEPTIDES
is an unbranched chain of amino acid, each joined to the next by a peptide bond.  They are classified by the number of amino acid present in the chain, e.g., dipeptide (contains two amino acids), tripeptide (contains three amino acids), oligopeptide (contains 10 to 20 amino acid residues and the name polypeptide is used to refer to longer peptides.  POLYPEPTIDE, is a long unbranched chain of amino acids, each joined to the next by a peptide bond.

NATURE of the PEPTIDE bond

Peptide bonds
the bonds that link amino acids together Covalent bond between the carboxyl group of one amino acid and the amino group of another amino acid In all peptides, long or short, the amino acid at one end of the amino acid sequence has a free H N group, and the amino acid at the other end of the sequence has a free COO group. Where; * the end with the free H N group is called the N- terminal end. * the end with the free COO group is called the C- terminal end

AMINO ACID RESIDUE

The portion of an amino acid structure that remains after the release of H O, when on an amino acid participates in peptide bond formation as it becomes part of a peptide chain.

Converting an abbreviated peptide Formula to a structural formula

Draw the structural formula for the tripeptide Ala- Gly- Val. Step 1. The N- terminal end of the peptide involves alanine. Its structure is written first Step 2. The structure of glycine is written to the right of the alanine structure , and a peptide bond is formed between the 2 amino aids by removing the element H2O & Bnding the N of glycine to the carboxyl C of alanine. Step 3. To the right of the just- formed peptide , draw the structure of aline.Then repeat step 2 to form the desired triteptide

PEPTIDE NOMENCLATURE
IUPAC rules for naming small peptides: RULE 1: The C- terminal amino acid residue ( located at the far right of the structure) keeps it full amino acid name. RULE 2: All of the other amino acid residues have names that end in yl . The yl suffix replaces the ine or ic acid ending of the amino acid name , except for trytophan ( trytophyl ), cysteine ( cysteinyl ), glutamine ( glutaminyl ), and asparagine ( asparaginyl ). RULE 3: The amino acid naming sequence begins at the N- terminal amino acid residue.

 Assign IUPAC names to the small peptide.

Glu- Ser- Ala

Solution: glutamic acid becomes glutamyl serine becomes seryl alanine remains alanine Answer:

glutamylserylalanine

Isomeric Peptides
 Peptides that contain the same amino acids but in different order are different molecules ( constitutional isomers ) with different properties  The number of peptides possible increases rapidly as the length of the peptide chain increases.

Biochemically Important Small Peptides

Small Peptide Hormones
Oxytocin -- plays a role in stimulating the flow on milk in a nursing mother. - regulates uterine contractions & lactations

Vasopressin regulates the excretion of water by the kidneys, it also affects blood pressure.

Enkephalins- pentapide neurtransmitters produced by the brain itself that bind at receptor sites in the brain to reduce pain.

Two best known enkephalins:

Met- enkephalin: Tyr-Gly- Gly- Phe- Met

Leu- enkephalins: Tyr-Gly- Gly- Phe-Leu

The two enkephalins differ structurally only in the amino acid at the end of the chain

Naturally occuring Enkephalins

Morphine & Codeine

Small Peptide Antioxidants

Glutathione ( Glu-Cys-Gly )

- A triteptide present in significant concentrations in most cells & is of considerable physiological importance as a regulator of oxidation reduction reactions. - functions as an antioxidant , protecting cellular ccontents from oxidizing agents such as peroxides & superoxides ( highly reactive forms of oxygen often generated within the cell in response to bacterial invasion ) BHA & BHT & - carotene

General Structural Characteristics of Proteins

 Protein - a peptide in which at least 40 amino acid residues are
present. - The second type of biochemical polymer, the first one was polysaccharides. - Protein monomers are amino acids , whereas polysaccharide monomers are monosaccharides. - Over 10,000 amino acid residues are present in several proteins; small proteins contain 40-100 amino acid residues.

Classification of protein based on peptide chain present

Monomer Protein Protein in which only one peptide chain is present Multimetric Protein - Protein in which more than one peptide chain is present Protein subunits - is the peptide chain present in in multimetric proteins

Classification of protein based on chemical composition

Simple protein- a protein in which only one amino acid residues

are present

Conjugated protein- protein that has one or more non-amino acid

entities present in its structure in addition to one or more peptide chains.

Prosthetic group- non-amino acid components that may be organic or inorganic. - non-amino acid group present in a conjugated protein

TYPES OF CONJUGATED PROTEINS

Class
Hemoproteins
Lipoproteins

Prosthetic Group
Hemi unit Lipid

Specific Example
Hemoglobin Myglobin LDL HDL Gamma globulin Mucin Interferon

Function of example
Carrier of O2 in blood O2 binder in muscles Lipid carrier Lipid carrier Antibody Lubricant in mucous secretions Antiviral protection Enzyme in glycogen phosphorylation Site for protein synthesis Self-replicating infection complex Storage complex for iron Enzyme in alcohol oxidation

Glycoproteins

Carbohydrate

Phosphoproteins Nucleproteins

Phosphate group Nucleic Acid

Glycogen Phosphorylase Ribosomes Viruses Iron-ferritin Zincalcoholdehydrogenase

metalloproteins

Metal Ion

Primary Structures Of Proteins

Primary protein structure-is the order in which amino acids linked together in a protein. -always involves more than just the numbers & kinds of amino acids present. -Involves the order of attachment of the amino acids to each other through peptide bonds. - Primary protein structure of a specific protein is always the same regardless of where the protein is found within an organism. -The structures of certain proteins are even similar among different species of animals. Insulin- First protein for which the primary structure was determined.

Secondary Structure Of Proteins

 Secondary protein structure- is the arrangement in space adopted by the backbone portion of a protein.
- Interactions involve the peptide linkages between amino acid residues

2 Most common types:

Alpha Helix ( helix ) Beta Pleated Sheet ( pleated sheet ) The Alpha Helix ( helix ) Structure - Protein secondary structure in which a single protein chain adopts a shape that resembles a coiled spring ( helix ), with the coil configuration maintained by hydrogen bonds. - The hydrogen bonding present in an helix is intramolecular.

 The pleated sheet structure

A protein secondary structure in which two fully extended protein chain segments in the same or different molecules are held together by hydrogen bonds. - Found extensively in the protein of silk U- turn Structure - Most frequently encountered type of pleated sheet structure

Tertiary Structure Of Proteins

Tertiary protein Structure- the overall three-dimensional shape of a protein that
results from the interactions between amino acid side chains ( R groups ) that are widely separated from each other within a peptide chain.

Four types of attractive interactions contribute to the tertiary structure of a protein:

I. II. III. IV. Covalent disulfide bonds ( strongest ) Electrostatic interactions ( salt bridges ) Hydrogen Bonds ( occur between amino acid with R groups ) Hydrophobic attractions ( results when 2 nonpolar side chains are close to each other )

Quaternary Structure
- The organization among the various peptide chains in a multimeric proteins. - The three dimensional shape of a protein consisting of 2 or more independent peptide chains, which results from noncovalent interaction between R groups.

Protein Classification Based on Shape

 Three main types of proteins based on molecular shape Fibrous protein- a protein whose molecules have an elongated shape with one dimension much longer than the others. - Tend to have simpler, regular , linear structures . Globular protein- a protein whose molecules have peptide chains
that are folded into spherical or globular shapes. - Water soluble substances

Membrane protein- a protein that is found associated with a

membrane system of a cell. -have a structure somewhat opposite of that globular proteins - water-insoluble & usually have fewer hydrophobic amino acids than globular-proteins.

Some Common Fibrous & Globular Proteins

Name
FIBROUS PROTEINS ( insoluble )

Occurences & Function

Found in wool,feathers,hooves,silk & fingernails Found in tendons,bone & other connective tissue Found in blood vessels & ligaments Found in muscle tissue Found in blood clots

Keratins Collagens Elastins Myosins Fibrin

GLOBULAR PROTEINS ( soluble )

Insulin Myoglobin Hemoglobin Transferrin Immunoglobins

Controls glucose metabolism Involved in Oxygen storage in muscles Involved Oxygen transport in blood Involved iron transport in blood Involved in immune system responses

- keratin
A fibrous protein particularly abundant in nature

Major protein constituent of hair, feathers, wool, fingernails and toenails, claws, scales,horns,turtle shells, quills , & hooves THE COILED COIL STRUCTURE OF THE - keratin.

Collagen
 The most abundant of all proteins in humans ( 30 % of total body protein )  Major structural material in tendons, ligaments, blood vessels, and skin.  Organic component of bones & teeth

Tissue
Achilles Aorta Bone ( mineral- free ) Cartilage Cornea Ligament Skin

Collagen (% by mass )
86 12-24 88 46-63 68 17 72

Hemoglobin
 a globular protein that transports oxygen from the lungs to tissue.  Tetramer,has four peptide chains & four heme units
STRUCTURE OF THE HEME GROUP:

Myoglobin
 A globular protein that functions as an oxygen storage molecule in muscles.  Monomer , consist of a single peptide chain & a heme unit.  Has higher affinity for oxygen than does hemoglobin

Protein Hydrolysis
 When a protein or smaller peptide in a solution of strong acid or strong base is heated, the peptide bonds of the amino acids are produced.  Hydrolysis reaction is the reverse of the formation reaction for a peptide bond.  Protein hydrolysis produces free amino acids  The process is the reverse of protein synthesis, where free amino acids are combined.  Hydrolysis of a protein in acidic solution: H+ H+ Protein + H2O ------------- smaller peptides--------------amino acids

Protein Denaturation
 Is the partial or complete disorganization of a proteins characteristics threedimensional shape as a result of disruption of its secondary, tertiary, and quaternary structural interactions.  The result of denaturation is loss of biochemical activity,loss of the proteins three-dimensional structure.Complete loss of such structure produces an unsaturated protein stand.  It does not affect the primary structure of a protein  Loss of water solubility is a frequent physical consequence of protein denaturation.  Renaturation- restoration process, in which the protein is refolded  Coagulation- the precipitation out of biochemical solution of denatured protein.  EXAMPLE of protein denaturation: Egg white is poured onto a hot surface Protein-containing foods are cooked Process of giving a hair permanent

Glycoproteins
 Is a Protein that contains carbohydrates or carbohydrate derivatives in addition to amino acids  When boiled in water , under basic conditions, it is converted to the water-soluble protein gelatin.  Include a number of very important substances: TWO OF THESE: Collagen & Immunoglobins

Collagen
Classified ads glycoprotein because of the presence of of carbohydrate units in its structure.

Immunoglobins
 Are among the most important & interesting of the soluble proteins in the human body  Is a glycoprotein produced by an organism as a protective response to the invasion of microorganisms or foreign molecules  Serves as antibodies to combat invasion of the body by antigens . Antigen- a foreign substance , such as bacterium or virus, that invades the human body. Antibody- a biochemical molecule that counteracts a specific antigen.

Lipoproteins
 Is a conjugated protein that contains lipids in addition to amino acids.  Major function is to help suspend lipids & transport them through the bloodstream.  Insoluble in blood because of their non-polar nature  The density is related to the fractions of protein & lipid material present.The greater the amount of protein in the lipoprotein, the higher the density

 PLASMA LIPOPROTEIN
- A lipoprotein that is involved in the transport system for lipids in the bloodstream.

Four major classes of plasma lipoproteins:

Chylomicrons
Transport dietary triacylglycerols from the intestine to the liver & to adipose tissue. Transport triacylglycerols synthesized in the liver to adipose tissue

Very-low-density lipoproteins (VLDL)

-

Low-density lipoproteins ( LDL )

-Transport cholesterol synthesized in the liver to cells througut the body.

High-density lipoproteins ( HDL )

- Collect excess cholesterol from body & tissues & transport it back to the liver for degradation to bile acids.

SOURCE OF ENERGY: PROTEIN

 Each gram of protein provides 4 calories

 Protein regulates osmotic pressure, hence water balance & acid- base balance

 Helps in the exchange of nutrients & other metabolites which pass between cells & the intercellular fluids or between tissues & the blood or lymph( extracellular fluids )

Protein Energy Malnutrition ( PEM)

 Two deficiency diseases caused by a grossly inadequate supply of protein or energy.or both.

MARASMUS
Condition resulting from from severe malnutrition, afflicts very young children who lack both energy & protein foods as well as vitamins & minerals.

Kwashiorkor
Appears when there is a sudden or recent lack of protein containing food. Causes fat to accumulate in the liver