Proteins and Amino Acids

• Proteins are the most abundant and functionally diverse molecules in living systems.
• Virtually every life process depends on them.

Functions of proteins:

• Catalysis: Enzymes
• Structural: Keratin, Collagen
• Transport: Hemoglobin
• Trans-membrane transport: Na+/K+ ATPases
• Hormones: Insulin
• Contractile function: actin, myosin
• Defense: Antibodies
• Storage: Casein and Ferritin

Amino Acids

• Proteins consist of polymers of amino acids.
• Amino acids are the building blocks of proteins.
• More than 300 different amino acids exist in nature, but only 20 are commonly found in mammalian proteins.
• The term "amino acid" is short for a-amino [alpha-amino] carboxylic acid.
• Amino acids share a basic structure: a central alpha carbon atom, a basic amino group (NH2), a carboxyl group (COOH), and a hydrogen atom.
• Amino acids differ from each other in the chemical structure of their R group.

Specialized Amino Acids

• Proline's side chain and a-amino N form a rigid, five-membered ring structure.
• Proline has a secondary amino group rather than a primary one and is referred to as an “imino acid.”
• The side chain of cysteine contains a sulfhydryl (thiol) group (–SH).
• The -SH groups of two cysteines can be oxidized to form a covalent crosslink called a disulfide bond (-S-S-).
• Two disulfide-linked cysteines are referred to as “cystine.”

Classification of Amino Acids

• Nutritional: Essential amino acids cannot be synthesized in the body, so they must be present in the diet.
• Non-essential: These amino acids can be synthesized in the body itself.
• Based on R group: can be nonpolar aliphatic, polar uncharged, aromatic, positively charged, or negatively charged
• Metabolic: can be ketogenic, glucogenic, or both

Amino Acids: R-Groups

• Non-Polar Aliphatic: R groups are aliphatic, nonpolar and hydrophobic
• Polar Uncharged: R groups more soluble in water or more hydrophilic
• Aromatic: R groups are aromatic and relatively nonpolar (hydrophobic).
• Acidic: Amino acids in which the R-group is acidic or negatively charged.
• Basic: Amino acids in which the R-group is basic or positively charged.

Nutritional Classification of Amino Acids

• Essential amino acids cannot be synthesized in the body and must be obtained through the diet.
• Non-essential amino acids can be synthesized by the body.

Metabolic Classification of Amino Acids

• Glucogenic amino acids break down to form glucose.
• Ketogenic amino acids break down to form ketone bodies.
• Glucogenic and ketogenic amino acids break down to form precursors for both glucose and ketone bodies.

Optical Properties

• The a-carbon atom with four distinct constituents is said to be chiral or asymmetric thus called an optically active carbon atom.
• All common amino acids are optically active except glycine since its a-carbon atom is not a chiral center with its R-group being a hydrogen atom.
• Chirality describes the ability of a molecule to rotate the plane of polarized light either to the right (dextrorotatory) or to the left (levorotatory).
• Amino acids with an asymmetric center at the a-carbon can exist in two forms, designated D and L, which are mirror images of each other.
• All of the amino acids found in proteins are L-a-amino acids and D-amino acids are found in polypeptide antibiotics.

Acid –Base Properties

• Amino acids form zwitterions (dipolar ions) at neutral pH (7.4).
• Zwitterions can act as acids (proton donors) and bases (proton acceptors) and are often called ampholytes
• In zwitterions of amino acids with uncharged side chains, the positive and negative charges cancel one another out.
• When rates of the opposing charges are balanced, molecules reach an isoelectric point.
• Amino acids are insoluble at their isoelectric point.

Peptide Bond Formation

• Each protein consists of one or more polypeptide chains.
• Each polypeptide chain is made up of amino acids, linked together in a specific order.
• During peptide bond formation, the carboxylic group of one amino acid condenses with the amino group of another, releasing a water molecule and forming a peptide bond.
• Each bond forms in a dehydration synthesis (condensation) reaction, where an OH- is lost from one part and a H+ from another to form an amide.

Peptide Bonds

• Amino acids are joined by a series of peptide bonds.
• After being incorporated into a peptide, the individual amino acids are referred to as amino acid residues.
• Small polymers of amino acids (less than 50) are called oligopeptides, and (more than 50) are referred to as polypeptides.
• A polypeptide chain has directionality, meaning that it has two chemically distinct ends.
• The end with a free amino group is the amino terminus (or N-terminus), and the end with a free carboxyl group is the carboxyl terminus (or C-terminus).
• The free amino end (N-terminal) of the peptide chain is written left, and the free carboxyl end (C-terminal) is written right.
• Amino acid sequences are read from the N-terminal end to the C-terminal end of the peptide.
• The names of peptides reflect the names of the amino acid residues involved.
• Begin at the N terminus, using -yl. All residues except the last are from the -yl suffix of acyl groups.

Peptide Nomenclature

• For a peptide the names of peptides reflect the names of the amino acid residues involved.
• Beginning at the N terminus. all except the last are given the -yl suffix of acyl groups.
• For example, alanylserine. The following dipeptide is named Each amino aid name has an associated three-letter abbreviation and a one letter symbol
• All proteins are made up of combinations of the 20 amino acids .

Protein Structures

• Bradykinin has the abbreviated name: Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
• The one letter symbol is RPPGFSPFR The hierarchy is as follows
• Primary Structure
• Secondary Structure
• Tertiary Structure
• Quaternary Structure

Primary structure of proteins

• The primary structure is the linear sequence of amino acids
• Understanding is important because diseases are a result of abnormal amino acid sequences
• The primary structure is specific and unique for a particular protein and thus determines its properties

Secondary Structure

• The polypeptide chain backbone does not assume a random conformation in the protein but usually forms regular arrangements of amino acids-located near one another in the linear sequence
• Alpha helix, Beta sheet, and Beta bend are examples of secondary structures.

Alpha Helix

• the protein chain forms a tightly packed coil
• stabilized by intrachain hydrogen bonds
• contains 3.6 amino acids per turn

Interrupting Structures

• Proline, disrupts the a-helix because of its structure-inserts a kink
• Charged Amino acids destabilize because of electrostatic interactions

Beta Sheets

• composed of two or more polypeptide chains arranged side by side .Stabilized by hydrogen bonding between polypeptide strands
• can be parallel or anti-parallel

Bends

• Bends reverse direction of polypeptide chain to produce compact, globular structure
• usually located on surface of molecule so contain charged residues - Proline & Glycine

Tertiary structures

• refers to the folding of the protein into a compact structure
• hydrophobic side chains buried away from water and hydrophilic groups are on the surface
• are stabilized by hydrophobic interactions, hydrogen bonds, ionic bonds, & disulfide bonds

Domains

• Most polypeptide chains folds into one or more compact region
• Are the fundamental structures of the polypeptide. May consist primarily of beta pleated sheets or a combination

Quaternary Structure

• Some proteins contain 2 or more polypeptide chains that may be Structurally identical or totally unrelated.
• Arrangement called “quaternary structure”
• Subunits-held together by covalent interactions.
• Hemoglobin is two alpha and two beta subunits.

Protein Folding

• Protein Folding is where Interacting Side Chains will cause Folding to give the shape.
• Each will attract or repulse eachother.

Denaturation

• Denaturation of proteins results in the unfolding of the secondary and tertiary structure in the protein.
• These structures are accompanied by mechanical mixing, strong acids or bases, detergents, organic solvents
• Denaturation may occur under extreme temperature
• However, most proteins are denatured in permanently disordered ways.