Amino Acids, Peptides and Proteins

Amino Acids

• Amino acids are the building blocks of proteins, and there are 20 standard amino acids.
• Each amino acid has a central carbon called the alpha-carbon, which is attached to four different groups: an amino group, a carboxyl group, a hydrogen atom, and a distinctive side chain.
• Amino acids can be classified based on their polarity, with four main categories: non-polar, uncharged polar, positively charged, and negatively charged.
• Essential amino acids cannot be synthesized by the human body and must be obtained through the diet, while non-essential amino acids can be synthesized.
• Amino acids have a tetrahedral structure, with a side chain carboxyl group, amino group, and alpha-carbon.

Structure of Amino Acids

• The alpha-carbon is chiral, except for glycine.
• Amino acids have a zwitterionic structure, with a positive charge on the amino group and a negative charge on the carboxyl group.
• Amino acids can be classified into different types based on their polarity, including:
  • Non-polar (hydrophobic): Alanine, Glycine, Proline, Phenylalanine, Tryptophan, Methionine, Leucine, Valine
  • Uncharged polar: Serine, Threonine, Glutamine, Asparagine, Cysteine, Tyrosine
  • Positively charged (basic): Lysine, Arginine, Histidine
  • Negatively charged (acidic): Aspartic acid, Glutamic acid

Functions of Amino Acids

• Amino acids are the building blocks of proteins.
• They are precursors to a variety of nitrogen-containing molecules.
• They are a source of energy.
• They are components of certain types of proteins.
• They can act as chemical messengers, such as neurotransmitters.
• They can be part of hormone derivatives.

Classification of Amino Acids

• Amino acids can be classified based on their polarity, as mentioned earlier.
• They can also be classified as essential or non-essential, based on whether the human body can synthesize them.

Physical Properties of Amino Acids

• Amino acids are soluble in water.
• They have a melting point.
• They have a taste, with some being sweet and others being bitter.
• They have an optical property, with all standard amino acids having a chiral center.
• They have an ultraviolet absorption spectrum.

Isoelectric Point of Amino Acids

• The isoelectric point (pI) is the pH at which an amino acid has no net charge.
• The pI is influenced by the ionic states of the alpha-carboxyl and alpha-amino groups and any ionizable groups in the side chains.

Titration of Amino Acids

• Titration involves the gradual addition or removal of protons.
• It is used to predict the charge of an amino acid at a given pH.
• It is used to devise a procedure for separating amino acids based on their charges.

Peptides

• Peptides are amino acid polymers with a molecular weight of several thousand to millions of daltons.
• They are involved in the neuroendocrine system as hormones, hormone releasing factors, neuromodulators, or neurotransmitters.
• Examples of peptides include:
  • Glutathione
  • Oxytocin
  • Vasopressin
  • Metenkephalin
  • Leuenkephalin
  • Atrial natriuretic factor
  • Substance P
  • Bradykinin
  • Glucagon
  • Corticotrophin
  • L-aspartylphenylalanylmethyl ester (aspartame)

Proteins

• Proteins are complex, organic nitrogenous substances with high molecular weights.
• They are essential constituents of all organisms.
• They are derived from Greek word "proteios", meaning primary or holding first place.
• Functions of proteins include:
  • Enzymatic catalysis
  • Transport and storage
  • Coordinated motion
  • Mechanical support
  • Immune protection
  • Generation and transmission of nerve impulses
  • Control of growth and differentiation
  • Cell signalling
  • Hormones
  • Major components of biological membranes

Classifications of Proteins

• Based on composition, physical and chemical properties:
  • Simple proteins
  • Conjugated proteins
  • Derived proteins
• Based on the shape and physical characteristics of the protein:
  • Fibrous proteins
  • Globular proteins
• Based on biologic function:
  • Enzymes
  • Storage proteins
  • Regulatory proteins
  • Structural proteins
  • Protective proteins
  • Transport proteins
  • Contractile or motile proteins
  • Exotic functions of proteins (e.g. monellin, antifreeze protein, resilin)

Structure of Proteins

• Formation of the peptide bond:
  • Amide linkages between the alpha-carboxyl group of one amino acid and the alpha-amino group of another
  • Individual amino acids are called amino acid residues
  • The residue with a free amino group at the leftmost residue is called the amino terminus or N-terminal
  • The residue with a free carboxylate group at the right is called the carboxyl terminus or C-terminal
• Nomenclature:
  • Peptides are named from the sequence of constituent amino acids
  • Beginning at the left with the N-terminal residue towards the C-terminal residue at the right
  • Amino acid residues in polypeptides are named by dropping the suffix -ine or -ate in amino acid and replacing by -yl except for C-terminal amino acid
  • -ine ending indicates its alpha carboxyl group not involved in peptide bond formation
• Levels of structural organization:
  • Primary structure: the linear sequence of amino acid residues linked by peptide bonds
  • Secondary structure: due to the formation of hydrogen bonds between peptide bonds
  • Tertiary structure: the 3-dimensional structure of proteins
  • Quaternary structure: the arrangement of multiple polypeptide chains in a protein

Primary Structure

• The linear sequence of amino acid residues linked by peptide bonds
• Important because many genetic diseases result in proteins with abnormal amino acid sequences
• Deals with:
  • Quantitative amino acid composition
  • Sequence of amino acid
  • Number of peptide chains

Secondary Structure

• Due to the formation of hydrogen bonds between peptide bonds
• Two types:
  • Coils or helices: brought by intrachain hydrogen bonding
  • Sheets or pleats: brought by interchain hydrogen bonding

Tertiary Structure

• Refers to the 3-dimensional structure of proteins
• Indicates how secondary structural features assemble to form domains and how they relate to each other
• Types of proteins in tertiary structures:
  • Fibrous: has structural roles
  • Globular: contains several types of secondary structure in the same polypeptide chain### Protein Folding and Modification
• Peptidyl prolyl cis-trans isomerase accelerates protein folding.
• Protein disulfide isomerase occurs mainly in the endoplasmic reticulum.

Levels of Structural Organization of Proteins

• Quaternary structure is exhibited by proteins containing more than one polypeptide chain.
• The arrangement of polypeptide subunits or chains is held together by non-covalent interactions like hydrophobic interactions, electrostatic interactions, and hydrogen bonds.

Life Cycle of Proteins

• The life cycle of a protein begins with synthesis on a ribosome, whose primary structure is dictated by mRNA.
• As synthesis proceeds, the polypeptide chain folds into its native conformation.
• Folding may be accompanied by processing events like proteolytic cleavage or the formation of disulfide bonds.
• Subsequent covalent modifications may attach molecules like fatty acids for translocation to a membrane.
• Binding an allosteric effector may trigger the adoption of a catalytically active conformation.
• Over time, proteins get damaged by chemical attack, deamidation, or denaturation.
• Damaged proteins may be "labeled" by the covalent attachment of several ubiquitin molecules and subsequently degraded to their component amino acids.

Protein Misfolding

• Protein misfolding results in improperly folded molecules that are tagged and degraded within the cell.
• Amyloid disease is caused by a mutation in a particular gene that produces an altered protein, leading to the formation of long, fibrillar protein assemblies consisting of β-pleated sheets.
• Prion disease is a fatal neurodegenerative disease characterized by spongiform changes, astrocytic gliomas, and neuronal loss from the deposition of insoluble protein aggregates in neuronal cells.

Protein Analysis

• Protein analysis involves partial breakdown into manageable fragments followed by stepwise analysis from one end of the chain to the other.
• Steps involved in protein analysis include purification of protein, determining amino acid composition, determining N and C terminals, determining amino acid sequence, checking the number of polypeptides, and chromatography.

Protein Purification

• Characteristics of proteins that are used in separation procedures include solubility, charge, polarity, size, and binding capacity.
• Different chromatography techniques are used based on these characteristics, such as paper chromatography, thin layer chromatography, ion exchange chromatography, electrophoresis, hydrophobic interaction, gel filtration chromatography, ultracentrifugation, and affinity chromatography.

This quiz covers the basics of amino acids, including types, functions, and their role in forming proteins. Learn about standard and non-standard amino acids, peptides, and proteins.