Chapter 5: Proteins

CHAPTER 5: PROTEINS

PROTEINS

  • Proteins are naturally occurring, unbranched polymers composed of amino acid monomer units.

  • Characteristics of Proteins:
      - Proteins are the most abundant substances in nearly all cells, second only to water.
      - They consist of the elements carbon (C), hydrogen (H), oxygen (O), and nitrogen (N); most also contain sulfur (S).
      - Specific proteins, such as casein, contain phosphorus (P).
      - Hemoglobin uniquely contains iron (Fe).

FUNCTIONS OF PROTEINS

Proteins serve several essential functions:

  • Enzymes: Catalysts for biochemical reactions.

  • Defense Proteins: Function in immune response.

  • Transport Proteins: Facilitate the movement of substances across cell membranes or within organisms.

  • Structural Proteins: Provide support and shape to cells and tissues.

  • Movement Proteins: Assist in muscle contraction and movement.

  • Nutrient Proteins: Serve as a source of amino acids and energy.

AMINO ACIDS

  • Amino acids are organic compounds containing both an amino (—NH₂) group and a carboxyl (—COOH) group.

  • An α-amino acid is characterized by having the amino and carboxyl groups attached to the same alpha-carbon atom.

  • The R group refers to the side chain specific to each amino acid, which determines its properties such as size, shape, charge, acidity, presence of functional groups, hydrogen bonding ability, and chemical reactivity.

PROPERTIES OF AMINO ACIDS

  1. Chirality of Amino Acids:
       - All amino acids (except glycine) are chiral, meaning they have asymmetrical structures.
       - 19 of the 20 standard amino acids possess a chirality center, leading to the existence of enantiomeric forms.
       - D-configuration: Found in bacterial cell walls and antibiotics.
       - L-configuration: The configuration of all amino acids that are incorporated into proteins.

COMMON AMINO ACIDS AND THEIR ABBREVIATIONS

  • A summary table of common amino acids is as follows:
      | Amino Acid | Three-Letter Abbreviation | One-Letter Abbreviation |
      |------------------|--------------------------|-------------------------|
      | Alanine | Ala | A |
      | Arginine | Arg | R |
      | Asparagine | Asn | N |
      | Aspartic Acid | Asp | D |
      | Cysteine | Cys | C |
      | Glutamic Acid | Glu | E |
      | Glutamine | Gln | Q |
      | Glycine | Gly | G |
      | Histidine | His | H |
      | Isoleucine | Ile | I |
      | Leucine | Leu | L |
      | Lysine | Lys | K |
      | Methionine | Met | M |
      | Phenylalanine | Phe | F |
      | Proline | Pro | P |
      | Serine | Ser | S |
      | Threonine | Thr | T |
      | Tryptophan | Trp | W |
      | Tyrosine | Tyr | Y |
      | Valine | Val | V |

CLASSIFICATION OF AMINO ACIDS

Classification based on different criteria includes:

  • Based on Polarity:
      - Non-Polar Amino Acids
      - Polar Neutral Amino Acids
      - Polar Acidic Amino Acids
      - Polar Basic Amino Acids

  • Based on Nutritional Value:
      - Essential Amino Acids: Cannot be synthesized by the body and must be obtained from the diet.
      - Non-essential Amino Acids: Synthesized by the body.

  • Based on Metabolic Fate:
      - Exclusively Ketogenic
      - Exclusively Glucogenic
      - Both Ketogenic and Glucogenic

NON-POLAR AMINO ACIDS

  • Non-polar amino acids are characterized by having a side chain that is hydrophobic and generally found in the interior of proteins to avoid water interaction.

  • They do not carry a net charge and can be either aromatic or aliphatic.

  • Examples include Glycine (Gly), Alanine (Ala), Valine (Val), Leucine (Leu), and Phenylalanine (Phe).

GLYCINE

  • Structure: R group is hydrogen (H).

  • Properties: Simplest amino acid and the only achiral amino acid.

  • Functions:
       - Important component of collagen.
       - Conjugated to bile acids, drugs, and other metabolites.
       - Serves as a major inhibitory neurotransmitter in the spinal cord.
       - Acts as an α-helix breaker.

ALANINE

  • Structure: R group is a methyl group (—CH₃).

  • Functions:
       - Major glucogenic amino acid.
       - Can be converted to pyruvate by transamination.
       - Plays a role in ammonia removal.

BRANCHED CHAIN AMINO ACIDS

  • Include Valine, Leucine, and Isoleucine, characterized by having branched side chains.

  • Function as alternative sources of energy.

PROLINE

  • Structure: Contains an aliphatic cyclic structure; nitrogen bonded to two carbon atoms.

  • Function: Acts as an α-helix breaker and is categorized as the only imino acid.

METHIONINE

  • Structure: R group is methylthioether group.

  • Functions:
       - It is the start codon (AUG).
       - Involved in the transfer of methyl groups as S-adenosylmethionine (SAM).
       - Converts norepinephrine to epinephrine.

PHENYLALANINE

  • Structure: R group is a benzyl group.

  • Hydrophobic nature: Most hydrophobic among aromatic amino acids.

  • Functions: Converted to tyrosine via the action of phenylalanine hydroxylase.

TRYTOPHAN

  • Structure: R group includes an indole ring.

  • Functions: Precursor for serotonin, melatonin, and vitamin B3 (Niacin).

POLAR AMINO ACIDS

  • Characterized by hydrophilic side chains with varying degrees of affinity for water.

  • Categories:
      - Polar Neutral: e.g., Tyrosine, Serine, Threonine.
      - Polar Acidic: e.g., Aspartic acid, Glutamic acid.
      - Polar Basic: e.g., Histidine, Lysine, Arginine.

POLAR NEUTRAL AMINO ACIDS

  • Amino acids that contain a polar but neutral side chain, meaning there are no additional acidic or basic properties. Examples include Serine and Threonine, which contain hydroxyl groups.

POLAR ACIDIC AMINO ACIDS

  • Contain one amino group and two carboxyl groups, resulting in a side chain with a negative charge.

  • Examples include Aspartic acid and Glutamic acid.

POLAR BASIC AMINO ACIDS

  • Contain two amino groups and one carboxyl group, leading to a side chain with a positive charge. Examples include Lysine, Histidine, and Arginine.

ESSENTIAL AND NON-ESSENTIAL AMINO ACIDS

  • Non-Essential Amino Acids: can be synthesized in the body. Examples include Alanine, Arginine, Asparagine, Glutamate, Glutamine, Glycine, Proline, Serine, and Tyrosine.

  • Conditionally Essential Amino Acids: amino acids that may be synthesized in the body but not in sufficient quantities. Examples include Arginine and Histidine.

AMINO ACID METABOLIC FATE

Exclusively Glucogenic Amino Acids: Convert to pyruvate or intermediates like oxaloacetate or succinyl-CoA, acting as glucose precursors.

  • Examples: Ala, Glu, Gln, His, Arg, Gly, Met, Val, Cys, Asn, Asp, Pro.

Exclusively Ketogenic Amino Acids: Catabolized to acetyl-CoA or acetoacetate for fatty acid or ketone production.

  • Purely Ketogenic Amino Acids: Leucine and Lysine.

Both Ketogenic and Glucogenic Amino Acids: Lead to varied metabolic products.

  • Examples include Tryptophan, Isoleucine, Phenylalanine, Threonine, and Tyrosine.

GENERAL STRUCTURAL CHARACTERISTICS OF PROTEINS

MONOMERIC AND MULTIMERIC PROTEINS

  • Monomeric Proteins: Composed of a single peptide chain.

  • Multimeric Proteins: Composed of multiple peptide chains (subunits), which can either be identical or different.

  • Example: Insulin is a multimeric protein with two subunits.

BASED ON CHEMICAL COMPOSITION

  • Simple Protein: Consists solely of amino acid residues.

  • Conjugated Protein: Contains non-amino acid entities along with peptide chains.

  • Prosthetic Group: The non-amino acid group attached to a conjugated protein.

TYPES OF CONJUGATED PROTEINS

Class

Prosthetic Group

Specific Example

Function

Hemoproteins

Heme Unit

Hemoglobin

Oxygen transport in blood

Lipoproteins

Lipid

Low-density lipoprotein (LDL)

Lipid transporter

Glycoproteins

Carbohydrate

Glycogen phosphorylase

Enzyme in glycogen breakdown

Phosphoproteins

Phosphate group

Casein

Nutrient storage

Nucleoproteins

Nucleic acid

Ribosomes

Protein synthesis site

Metalloproteins

Metal ion

Iron-ferritin

Iron storage

PEPTIDE FORMATION

  • Peptide Bond: Formed through a reaction between the amine group of one amino acid and the carboxylic acid of another. This reaction is known as a dehydration-condensation reaction.

LEVELS OF PROTEIN STRUCTURE

  • Primary Structure: The sequence of amino acids linked together by peptide bonds.

  • Secondary Structure: Spatial arrangement of the protein backbone, often forming alpha helices or beta-pleated sheets through hydrogen bonding.

  • Tertiary Structure: The three-dimensional shape of a protein formed by interactions between R groups (side chains).

  • Quaternary Structure: Organization of multiple peptide chains in multimeric proteins, maintained by noncovalent interactions such as hydrophobic interactions and hydrogen bonds.

PRIMARY STRUCTURE

  • The order of amino acids linked by peptide bonds forms the primary structure.

SECONDARY STRUCTURE

  • Arrangements such as the alpha helix and beta pleated sheet formed primarily through hydrogen bonding.

  • Alpha Helix: Resembles a coiled spring, maintained by hydrogen bonds between C=O and N—H groups.
      - Characteristics include:
        1. Right-handed twist.
        2. Hydrogen bonds parallel to the helix axis.
        3. Each turn, including 3.6 amino acids.
        4. Amino acid R-groups extend outward from the spiral.
        5. R-groups do not fit within the spiral.