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.

This quiz covers various aspects of proteins and amino acids, including their classification as heteropolymers and the significance of different amino acids in protein structure and function. Explore the primary, secondary, tertiary, and quaternary structures of proteins as well as the roles they play in living systems and their unique characteristics.