Introduction to Proteins

Proteins

• The term "protein" comes from the Greek word "proteios," which means "of primary importance."
• Swedish chemist Jöns Jakob Berzelius first described and named proteins in 1838.
• James B. Sumner demonstrated that the enzyme urease was a protein in 1926, which brought proteins' central role in living organisms to light.

Characteristics of Proteins

• A protein is a naturally occurring, unbranched polymer in which the monomer units are amino acids.
• Proteins are the most abundant molecules in cells after water, accounting for about 15% of a cell's overall mass.
• The elemental composition of proteins includes carbon (C), hydrogen (H), nitrogen (N), and oxygen (O), and most proteins also contain sulfur (S).
• The average nitrogen content of proteins is 15.4% by mass.
• Some specialized proteins contain iron (Fe), phosphorus (P), and other metals.

Amino Acids: The Building Blocks for Proteins

• An amino acid is an organic compound that contains both an amino (-NH2) and a carboxyl (-COOH) group attached to the same carbon atom.
• The position of the carbon atom is Alpha (a)
• The -NH2 group is attached at alpha (a) carbon atom.
• The -COOH group is attached at alpha (a) carbon atom.
• The "R" side chain varies in size, shape, charge, acidity, functional groups, hydrogen-bonding ability, and chemical reactivity.
• There are over 700 known amino acids.
• There are 20 standard amino acids based on common -r groups.

Amino Acid Classification Based on R-Group Properties

• Standard amino acids are divided into four groups based on the properties of their R-groups.

Non-Polar Amino Acids

• R-groups are non-polar.
• These amino acids are hydrophobic, meaning they are water-fearing and insoluble in water.
• Eight of the 20 standard amino acids are non-polar.
• These amino acids are located on the interior of proteins when present, where there is no polarity.

Polar Amino Acids

• R-groups are polar.
• There are three types of polar amino acids: polar neutral, polar acidic, and polar basic.
• Polar-neutral amino acids contain polar but neutral side chains. Seven amino acids belong to this category.
• Polar-acidic amino acids contain a carboxyl group as part of the side chains. Two amino acids belong to this category.
• Polar-basic amino acids contain an amino group as part of the side chain. Two amino acids belong to this category.

Amino Acid Nomenclature

• Common names assigned to the amino acids are currently used.
• Three-letter abbreviations for naming purposes are widely used.
• The first letter of the amino acid name is compulsory and capitalized, followed by the next two letters not capitalized, except for Asparagine (Asn), Glutamine (Gln), and tryptophan (Trp).
• One-letter symbols are commonly used to compare amino acid sequences of proteins.
• The first letter of the name is usually the one-letter symbol.
• When more than one amino acid has the same letter, the most abundant amino acid gets the first letter.

Essential Amino Acids

• Essential amino acids must be obtained from dietary sources because the human body cannot synthesize them in adequate amounts from other substances.
• The mnemonic "PVT TIM HALL" can be used to remember the essential amino acids: Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine, Leucine, and Lysine.
• Arginine is required for growth in children but is not an essential amino acid for adults.

Complete vs. Incomplete Dietary Protein

• A complete dietary protein contains all of the essential amino acids in the same relative amounts the body needs.
• Casein from milk and proteins from animal sources (meat, fish, and eggs) are examples of complete dietary proteins.
• Incomplete dietary proteins don't contain adequate amounts, relative to the body's needs, of one or more essential amino acids.
• Protein from plant sources, such as gelatin (Arg), are examples of incomplete dietary proteins.
• Common limiting amino acids include lysine (in wheat, rice, oats, and corn), methionine (in beans and peas), and tryptophan (in corn and beans).
• Soy is the only complete dietary protein common in plant proteins.

Complementary Dietary Proteins

• Two or more incomplete dietary proteins that, when combined, provide an adequate amount of all essential amino acids relative to the body's needs.
• Rice and beans are an example of complementary dietary proteins.

Chirality and Amino Acids

• In all standard amino acids except glycine, four different groups are attached to the α-carbon atom.
• In glycine, the R-group is hydrogen.
• Nineteen of the 20 standard amino acids contain a chiral center, and these chiral centers exhibit enantiomerism (left- and right-handed forms).
• Found amino acids in nature and proteins usually have the Lisomer form.
• Bacteria has some D-amino acids.
• With monosaccharides nature favors D-isomers.
• The COOH group is put at the top, the R group at the bottom to position the carbon chain vertically.
• The -NH2 group is in a horizontal position.
• Glycine, the simplest of the standard amino acids, is achiral.
• Ile and Thr have two chiral centers.
• Positioning NH2 on the left is the L isomer.
• Positioning NH2 on the right is the D isomer.

Acid-Base Properties of Amino Acids

• In pure form, amino acids are white crystalline solids that decompose before they melt and are not very soluble in water.
• Zwitterions are ions with positive and negative charges on the same molecule with a net zero charge.
• Carboxyl groups give up a proton to become negatively charged, while amino groups accept a proton to become positively charged.
• In solution, amino acids exist in three different species: zwitterions, positive ions, and negative ions. The equilibrium shifts with changes in pH.
• The isoelectric point (pI) is the pH at which the concentration of the zwitterion is maximal, and the net charge is zero.
• Different amino acids have different isoelectric points.
• At the isoelectric point, amino acids are not attracted to an applied electric field because they have a net zero charge.

Cysteine: A Chemically Unique Amino Acid

• Cysteine is the only standard amino acid with a sulfhydryl group (-SH group).
• The sulfhydryl group gives cysteine a chemical property unique among the standard amino acids.
• In the presence of mild oxidizing agents, cysteine dimerizes to form a cystine molecule.
• A cystine molecule consists of two cysteine residues linked via a covalent disulfide bond.

Naming Conventions

• Glysine, a - amino ethanoate, abbreviated as GLY
• Alanine, a - amino propionate, abbreviated as ALA
• Valine, a - amino isovalerate, abbreviated as VAL
• Leucine, a - amino isocaproate, abbreviated as LEU
• Isoleucine, a - amino b - methyl-valerate, abbreviated as ILE
• Serine, a - amino b – hydroxy propionate, abbreviated as SER
• Threonine, a - amino b - hydroxy butyrate, abbreviated as THR
• Aspartic Acid, a - amino succinate, abbreviated as ASP
• Glutamine , a - amino g -glutaramide, abbreviated as GLN
• Lysine, a, e – diamino caproate, abbreviated as LYS
• Arginine, a - amino d -guanidine valerate, abbreviated as ARG
• Histidine, a - amino b - imidazole propionate, abbreviated as HIS
• Cysteine, a - amino b- mercapto propionate, abbreviated as CYS H
• Cystine, Di(a - amino b- mercapto propionate), abbreviated as CYS-CYS
• Methionine, a - amino g- methyl mercapto butyrate, abbreviated as MET
• Phenylalanine, a -amino b - phenyl propionate, abbreviated as PHE -Tyrosine, a - amino b - [p -hydroxyphenyl], abbreviated as TYR
• Tryptophan,(. - amino b - indolepropionate), abbreviated as TRP
• Proline, abbreviated as PRO, Proline (PRO) (2- carboxy pyrollidine)
• Hydroxyproline (HYPRO) (2- carboxy-4-hydroxy-pyrollidine)

Peptides

• Under proper conditions, amino acids can bond to produce an unbranched chain of amino acids.
• The length of the amino acid chain can vary from a few to many amino acids.
• Peptides are chains of a covalently-linked amino acids.
• The covalent bonds between amino acids in a peptide are called peptide bonds.

Types of Peptides

• Dipeptide: A bond between two amino acids
• Oligopeptide: A chain of approximately 10-20 amino acids
• Polypeptide: A bond between a large number of amino acids
• N-terminal end and a C-terminal end: Every peptide has an N-terminal end and a C-terminal end.

Peptide Bonds

• A covalent bond is formed between the carboxyl group of one amino acid and the amino group of another amino acid.
• The repeating sequence of peptide bonds and a-carbon -CH groups in a peptide is referred to as the backbone of the peptide.

Peptide Nomenclature

• The C-terminal amino acid residue keeps its full amino acid name.
• The -yl suffix replaces the -ine or -ic acid ending of the amino acid name for all other of the amino acid residues, except for tryptophan, for which -yl is added to the name.
• The amino acid naming sequence starts with the N-terminal amino acid residue.
• For example: Ala-Leu-Gly, proper IUPAC name is alanylleucylglycine

Isomers

• Isomeric peptides contain the same amino acids but have different properties because they have a different sequence.
• Two different dipeptides can be formed between alanine and glycine
• As the length of the peptide chain increases, the number of isomeric peptides possible increases rapidly.

Bio-chemically active peptides

• Hormones
• Neurotransmitters
• Antioxidants

Small Peptide Hormones

• Oxytocin (uterine contraction) and vasopressin (controls amount of water) are among the best-known peptide hormones.
• The pituitary gland produces them.
• Nonapeptide: A nonapeptide (nine amino acid residues) with six of the residues held in the form of a loop by a disulfide bond formed between two cysteine residues

Small Peptide Neurotransmitters

• Pentapeptides - an example is Enkephalins.
• Enkephalins are produced by the brain to bind receptors and help reduce pain.
• Best-known enkephalins: Met-enkephalin: Tyr-Gly-Gly-Phe-Met and Leu-enkephalin: Tyr-Gly-Gly-Phe-Leu

Small Peptide Antioxidants

• Glutathione (Glu-Cys-Gly) a tripeptide
• Glutathione is present in high levels in most cells, regulators of oxidation-reduction reactions, and also an antioxidant; helps protects cellular components from oxidizing agents.
• Bonding of Glu to Cys : Glu is bonded to Cys through the side-chain carboxyl group.

General Structural Characteristics of Protein

• Proteins are peptides with at least 40 amino acid residues.
• Polypeptide and protein are often used interchangeably,
• Some proteins have more than 10,000 amino acid residues
• Common proteins contain 400-500 amino acid residues, whereas small proteins contain 40-100 amino acid residues.
• Monomeric proteins contain one peptide chain.
• Multimeric proteins contain more than one peptide chain, which are called protein subunits.

Protein Classification Based on Chemical Composition

• Simple proteins contain only amino acid residues.
• Subunits : all subunits contain only amino acids.
• Conjugated proteins contain one or more non-amino acid entities (prosthetic groups).
• One or more chains of Poly peptides may be present
• Prosthetic non-amino acid components can be organic or inorganic
• Lipoproteins contain lipid prosthetic groups
  • Glycoproteins contain carbohydrate groups
  • Metalloproteins contain specific metal as prosthetic group

Primary Protein Structure

• The order in which amino acids are linked together in a protein.
• Every protein has its unique amino acid sequence and order of attachment.
• Frederick Sanger (1953) sequenced and determined the primary structure for insulin.
• Six atoms: two amino acids are linked through a peptide bond.
• C-N bond: rotation of groups is hindered by Planar peptide linkage structure with considerable rigidity.
• Cis-trans isomerism is possible about C-N bond.
• The preferred orientation: The trans isomer