Biochem - M.D.

Protein Function

• Protein's function relies on its structure.
• Catalytic proteins, such as enzymes, speed up chemical reactions within the body.
• Transport proteins move molecules around the body; examples include hemoglobin, transferrin, and lipoproteins.
• Storage proteins act as reservoirs for molecules. Myoglobin and ferritin are examples.
• Defense proteins, like immunoglobulins, provide protection.
• Regulatory proteins maintain homeostasis in metabolic processes.
• Structural proteins, such as collagen and elastin, create a flexible framework for cells.

Amino Acids - Building Blocks

• Amino acids are the basic units that make up proteins.
• There are over 300 amino acids in nature, but DNA only encodes 20.
• Mammalian proteins are created using only 20 amino acids.
• All amino acids share common features, including an N-terminal amino group (NH2), a C-terminal carboxyl group (COOH), and an 'R' functional group.
• An amino acid's properties depends on its R group's chemical structure.
• Amino acid backbones have similar charge characteristics.
• The charge of amino acids is important to consider at physiological pH.

Amino Acid Forms and pH

• Amino acids can exist in different forms depending on pH:
  • At pH 1.0, amino acids are fully protonated with a net charge of +1.
  • At pH 7.0, amino acids are zwitterionic, having a net charge of 0.
  • At pH 11.0, amino acids are fully deprotonated and have a net charge of -1.
• Acidic conditions favor the positive ion form, where amino acids behave as bases, and the COO- ion gains a proton.
• Alkaline conditions favor the negative ion form, where amino acids act as acids, and the NH3+ ion loses a proton.

Amino Acid Categories

• 20 amino acids are used to form all proteins.
• Proteins are often further modified after synthesis through post-translational modification.
• Properties are determined by the R group structure.
• Nonpolar amino acids have aliphatic, lipid-like R-groups that do not bind or donate protons and do not form hydrogen bonds
• They participate in hydrophobic interactions, important for membrane proteins
• Nonessential amino acids are synthesized in the body.
• Essential amino acids must be obtained through the diet.
• Arginine and Histidine are considered essential only in young people.
• Use "PVT TIM HALL" to remember the essential amino acids: Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Arginine, Leucine, Lysine.
• Proline has a unique IMINO group that introduces kinks, disrupting structure.
• Serine, Threonine, and Tyrosine (Ser, Thr, Tyr) have polar -OH groups allowing them to attach to phosphate and oligosaccharide chains (O-linkage).
• Glutamine and Asparagine (Gln, Asn) have an amide group that form hydrogen bonds or bind with oligosaccharide chains (N-linkage).
• Serine's OH group is important in active enzyme sites.
• Cysteine is necessary for forming disulfide bonds, and SH oxidizes to create cystine dimers.
• Acidic amino acids can donate a proton (H+) and are negatively charged, having ionized R groups at physiological pH
• Basic can accept a proton (H+) and becomes positively charged, having ionized R groups at physiological pH
• Histidine is weakly positive and vital for transporting Oxygen.

Peptide Bonds and Protein Structure

• Amino acids are linked by peptide bonds to create proteins.
• A dipeptide has two amino acids, an oligopeptide contains between 2-10 amino acids, polypeptides contain 10-100 amino acids and proteins contain more than 100 amino acids.
• The peptide bond is stable.
• Partial double bond characteristics result from resonance structures.
• Peptide bonds are rigid and planar, with rotation possible only at the amide-α-carbon and carbonyl-α-carbon bonds.
• Two conformations exists: trans and cis.
• Trans configurations are favored.
• Peptide bonds are polar, which enables to form hydrogen bonds.
• Peptide bonds are strong.

Protein Structure

• Primary structure is the amino acid sequence without branching.
• Secondary structure involves the relationship between a sequence of amino acids -- alpha-helices and beta-sheets -- and is a result of hydrogen bonding between amino acid backbones.
  • Alpha helix structures are stabilized by H-bonding parallel to the helix's axis
  • Certain amino acids with bulky R groups or charges can disrupt the helix, and proline introduces kinks.
• Beta sheets involve extensive hydrogen bonding between linear regions of proteins that are perpendicular to the polypeptide backbone.
• The beta-bend is a 4 amino acid structure that allows the polypeptide chain to fold back on itself, containing proline.
• Tertiary structure occurs between regions of the protein (globular or fibrous) where proteins may consist of α-helices, β-pleated sheets, or both.
  • The tertiary structure is determined by the protein's primary structure.
• Quaternary structure involves multiple subunits joined by non-covalent interactions.

Tertiary structure interactions include:

• Hydrogen bonding takes place between amino acid side chains that have oxygen or nitrogen-bound hydrogen.
• Hydrophobic interactions take place only in aliphatic amino acids located in the protein's interior.
• Ionic interactions are caused by attraction between proteins with permanently charged residues
• Van der Waals attractions temporary dipole moments are caused by the random movement of electrons in a protein.
• Disulfide binding involves covalent linkage between 2 sulfhydryl groups of cysteine residues to produce a cystine residue.

Additional Points

• The 1°, 2°, and 3° structures are pre-determined by the linear sequence of amino acids (1° structure)
• Localization of different regions of proteins is based upon the properties of their functional groups - Non-Polar amino acids are hydrophobic (repel water) and form interactions with one another but not with aqueous environments - Polar amino acids are hydrophilic (attracted to water) and readily interact with aqueous environments via hydrogen bonding
• Denaturation involves heat, pH disruption, or detergents that disrupt non-covalent interactions causing it to lose its NATIVE conformation (3° Structure)
• Chaperones (Chaperonins) helps in folding the protein into the proper native conformation during protein synthesis.