Biochemistry: Proteins and Amino Acids

Proteins

• Proteins are heteropolymers of amino acids.
• They are the most abundant and functionally diverse molecules in living systems.
• Proteins account for up to 50% of the dry weight of most cells.
• Twenty different amino acids are commonly found in mammalian proteins.

Biomolecules

• Biomolecules are organic molecules formed by living organisms.
• They are primarily composed of carbon, hydrogen, oxygen, and nitrogen.
• Four major classes of biomolecules are lipids, proteins, carbohydrates, and nucleic acids.

Learning Outcomes

• Students will describe the various functions of proteins in the body.
• They will outline the structure of amino acids.
• Students will explain how amino acids are joined into peptides through peptide bonds.
• Understanding primary, secondary, tertiary, and quaternary protein structure is essential to grasping protein function.

Amino Acids

• Amino acids are classified by their R-group.
• The R-group can range from a simple hydrogen atom (as in glycine) to complex structures with many functional groups attached.
• The 20 common amino acids have different physical and chemical characteristics due to their unique R-group structures.
• Amino acids can be categorized further as polar, nonpolar, charged, or uncharged, all affecting their roles in protein structure and function.

Amino Acid Structure

• Amino acids have a central carbon atom (α-carbon).
• Attached to this central atom are an amino group (-NH2), a carboxyl group (-COOH), a hydrogen atom, and a side chain (R-group).
• The R-group (variant) distinguishes one amino acid from another in composition and properties. This accounts for their unique properties and roles in protein structure and function.
• This general structure is common to all amino acids besides one: proline. In Proline the R group also bonds back to the amino group.

Amino Acid Classification

• Amino acids are classified based on their R-group properties (polarity, charge, etc.).
• Common classifications include non-polar aliphatic, aromatic, polar uncharged, acidic, basic, and small.

Amino Acids with Nonpolar Side Chains

• Many nonpolar side chains have hydrocarbon structures as part of their R-groups.
• These hydrocarbons contribute to their hydrophobic character and interactions within proteins.
• Examples of these amino acids include Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Phenylalanine, Tryptophan.

Non-polar Aliphatic Amino Acid

• The side chain in nonpolar aliphatic amino acids is bonded to the amino nitrogen.
• Proline amino acid has a secondary amino acid (imino acid).
• The cyclic structure affects the resulting peptide conformation.

Uncharged Polar Side Chains

• These amino acids have polar but uncharged side chains.
• The polar nature contributes to their hydrophilic interaction with water.
• Serine, threonine, cysteine, tyrosine, asparagine, and glutamine are examples.
• Form hydrogen bonds.

Disulfide Bonds

• Two cysteine molecules can form a disulfide bond, a covalent S-S linkage.
• The disulfide bond helps stabilize many extracellular proteins like albumin.

Acidic Side Chains

• These amino acids have extra carboxyl groups.
• Examples include aspartate and glutamate.
• The extra carboxyl group contributes to the negative charge at neutral pH.

Amides of Aspartate and Glutamate

• Asparagine and glutamine are amides of aspartate and glutamate, respectively.
• They are polar, uncharged amino acids.

Basic Side Chains

• Histidine, lysine, and arginine have basic side chains.
• These side chains can change their charge based on the surrounding pH; at neutral pH, they exhibit a positive charge allowing hydrogen bonding.
• They often play key roles in enzyme active sites, catalyzing reactions by forming and breaking bonds.

Amino Acids with Special Properties

• Glycine's R-group is a hydrogen atom.
• It can fit into hydrophobic and hydrophilic environments.
• It increases the flexibility of the polypeptide chain.
• Proline has an amino group that forms part of a ring structure.
• The ring structure causes bends and kinks in the polypeptide chain; restricts rotation around the alpha-carbon.
• Cysteine contains a sulfhydryl group and can form disulfide bridges by linking to another cysteine.

Optical Properties of α-amino Acids

• Most amino acids have an asymmetric α-carbon which can exist as two mirrored isomers (D and L).
• Naturally occurring proteins only utilize the L-configuration.
• D-amino acids are found in some peptides found in bacterial cell walls.

Spectral Properties of Amino Acids

• Individual amino acids do not absorb visible light.
• Aromatic amino acids (tyrosine, tryptophan, phenylalanine) absorb UV light.
• UV absorption characteristics help quantify protein concentration.

Amino Acid Modification

• Amino acids can be chemically altered after synthesis.
• These modifications are called post-translational modifications.
• Additions include hydroxyl, phosphoryl, and methyl groups, among others.

Hydroxylation / Hydroxylysine and Hydroxyproline

• Additional hydroxyl groups can stabilize collagen fibres (hydroxyproline and hydroxylysine).
• Deficiency in vitamin C hinders hydroxylations.

Methylation

• Some proteins can attach methyl groups to amino acids.
• Histone methylation regulates gene expression.

Carboxylation

• Carboxylation adds carboxyl groups to glutamic acid.
• For instance, in prothrombin (clotting factor).
• Vitamin K deficiency prevents this and contributes to clotting problems.

Phosphorylation

• Phosphorylation adds a phosphate group.
• This can alter protein activity in various pathways.
• Phosphorylation sites commonly observed are on Serine, Threonine, Tyrosine.

Uncommon Amino Acids

• Additional amino acids exist but aren't protein building blocks.
• These amino acids function as intermediates in specific metabolic pathways. Examples include Orntihine and Citrulline.

Amino Acids are Zwitterions

• At neutral pH, the carboxyl group loses a proton, and the amino group gains a proton.
• This leads to a net zero charge with a net positive charge on the amino end, and a net negative charge on carboxyl end.

Ionization

• Amino acid ionization varies with pH changes.
• These ions act as proton donors (acids) or acceptors (bases) maintaining pH balance.

Polypeptides

• Amino acids join via peptide bonds in a condensation reaction.

Peptide Bond

• A peptide bond is a chemical bond formed between the carboxyl group of one amino acid and the amino group of another.
• Peptide bonds form a linear sequence of amino acids.
• The peptide bond has a partial double bond character which restricts rotation.

Polypeptides have Polarity

• Polypeptides have an N-terminus (amino acid end) and a C-terminus (carboxyl acid end).

Polypeptide Size Variation

• Polypeptide size differs significantly between proteins.

Protein Structure

• Proteins have four levels of structure.
• Primary: Sequence of amino acids.
• Secondary: Local folding patterns (alpha-helices, beta-sheets).
• Tertiary: Overall 3D shape of the protein.
• Quaternary: Structure of multiple polypeptide units.

Loops, Turns and Bends

• Loops, turns, and bends are segments that connect secondary structure regions.
• They often play roles in protein function.
• Many are on the surface of the protein.

Proteins with Chemical Groups

• Some proteins contain chemical groups beyond amino acids.
• These are called Prosthetic groups
• Examples include heme in hemoglobin and various lipids.

Dynamic Changes Within Proteins

• Conformational Changes are essential for protein function.
• These facilitate binding and catalytic activities. Changes are vital for enzymes.

Protein Denaturation

• Denaturation disrupts protein structure.
• Denaturation can be caused by altered PH, Temperature extremes, and chemicals like urea.
• Denatured proteins often lose their function. The structure is disrupted, not just slightly altered.