Amino Acids Overview

Amino Acids

• There are over 300 amino acids but only 20 are commonly found in mammalian proteins
• All amino acids have the same fundamental structure: a central carbon atom, an amino group (NH2), a carboxyl group (COOH) and a hydrogen atom
• The R group or side chain differentiates amino acids
• Amino acids can be classified into 6 categories: aliphatic side chains, OH groups, SH groups, basic groups, acidic groups, aromatic side chains

Aliphatic Side Chains

• Glycine (Gly, G) is the only amino acid with an achiral carbon due to its hydrogen side chain
• Glycine is used in heme synthesis, purine synthesis, and is a major inhibitory neurotransmitter in the SPINAL CORD
• Alanine (Ala, A) carries nitrogen from peripheral tissues to the liver
• Valine (Val, V), Isoleucine (Ile, I), and Leucine (Leu, L) are branched-chain amino acids whose metabolites accumulate in MSUD (Maple Syrup Urine Disease)

OH Groups

• Serine (Ser, S) is a phosphorylation site for enzyme modification
• Threonine (Thr, T) is linked to carbohydrate groups in glycoproteins
• Tyrosine (Tyr, Y) is a precursor of thyroxine and melanin

SH Groups

• Cysteine (Cys, C) contains a sulfhydryl group that is an active part of many enzymes
• Two cysteines can be connected by a covalent Disulfide bond to form Cystine
• Methionine (Met, M) transfers methyl groups as SAM

Basic Groups

• Histidine (His, H) is a precursor of histamine and is used in the diagnosis of Folic Acid Deficiency
• Arginine (Arg, R) is a precursor of Urea, Creatinine and Nitric Oxide
• Lysine (Lys, K) is involved in the production of collagen and elastin

Acidic Groups

• Aspartic acid (Asp, D) and Glutamic acid (Glu, E) are proton donors
• Asparagine (Asn, N) and Glutamine (Gln, Q) are involved in amino acid metabolism

Aromatic Groups

• Tryptophan (Trp, W) has the largest aromatic side chain
• Phenylalanine (Phe, F) accumulates in phenylketonuria

Imino Groups

• Proline (Pro, P) is a non-standard amino acid because its side chain is linked to the nitrogen group of the amino group
• Proline's structure contributes to the fibrous structure of collagen and interrupts α-helices in globular proteins

Nonpolar Side Chains

• Nonpolar side chains have a net charge of zero at physiologic pH
• They are not acidic or basic and do not bind or give off protons
• Nonpolar side chains promote hydrophobic interactions and cluster in the interior of proteins

Uncharged, Polar Side Chains

• Uncharged, polar side chains have a net charge of zero at physiologic pH
• They can form hydrogen bonds
• They are often found on the surface of proteins where they can interact with water molecules

Acidic Side Chains

• Acidic side chains are negatively charged at physiologic pH because of the carboxylate group
• They are proton donors and participate in ionic reactions
• Glutamate (Glu, E) is the precursor of GABA and Glutathione

Basic Side Chains

• Basic side chains are positively charged at physiologic pH because of the amine group
• They are proton acceptors and participate in ionic reactions

Selenocysteine, the 21st Amino Acid

• Selenocysteine is an L-α amino acid found in proteins such as peroxidases, reductases, selenoprotein P, and iodothyronine deiodinases

Optical Properties of Amino Acids

• All amino acids except Glycine are chiral
• L-configuration is found in proteins
• D-configuration is found in bacterial walls and antibiotics
• Stereoisomers/Isomers/Enantiomers are exact mirror images of each other

Charge of Amino Acids

• Amino acids can have a positive, negative, or zero charge depending on the pKa values and pH of the environment
• Zwitterion Molecule is a chemical compound with a total net charge of zero
• Isoelectric pH or Isoelectric Point is the pH where the zwitterion predominates

Essential Amino Acids

• Essential amino acids cannot be synthesized by the body and must be obtained from the diet
• Essential amino acids include: Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Arginine, Leucine, Lysine

Conditionally Essential Amino Acids

• Conditionally essential amino acids are not typically required but can become necessary under certain conditions
• Conditionally essential amino acids include: Arginine and Histidine

Protein Structures

• Proteins have four levels of structure: primary, secondary, tertiary, and quaternary

Primary Structure

• Primary structure refers to the linear sequence of amino acids in a polypeptide chain
• Peptide bonds connect the α-amino group of one amino acid to the α-carbonyl group of another
• Peptide bonds are very stable and can only be disrupted by hydrolysis or prolonged exposure to a strong acid/base at elevated temperatures

Secondary Structure

• Secondary structure refers to the local folding of the polypeptide chain into three-dimensional structures
• Two main types of secondary structure are α-helix and β-pleated sheets
• Secondary structure is stabilized by hydrogen bonding

Alpha-Helix

• The α-helix is a right-handed spiral structure with the polypeptide backbone core side chains extending outward
• The α-helix is stabilized by hydrogen bonds between the carbonyl and amino groups of the polypeptide backbone
• Proline, large R groups, and charged R groups disrupt the α-helix

Beta-Pleated Sheet

• The β-pleated sheet is formed by two or more polypeptide chains that are parallel to each other
• The β-pleated sheet is stabilized by hydrogen bonds between the carbonyl and amino groups of the polypeptide backbone
• The β-pleated sheet can be either parallel or antiparallel

Tertiary Structure

• Tertiary structure refers to the overall three-dimensional shape of a protein
• It refers to the folding of domains and their final arrangement in the polypeptide
• Tertiary structure is stabilized by disulfide bonds, hydrophobic interactions, and hydrogen bonds
• Examples of tertiary structures include globular proteins and fibrous proteins

Domains

• Domains are fundamental functional and three-dimensional structural units of a polypeptide
• Domains are formed by a combination of motifs

Quaternary Structure

• Quaternary structure refers to the arrangement of multiple polypeptide chains (subunits) in a protein complex
• Quaternary structure is stabilized by noncovalent bonds

Denaturation

• Denaturation is the disruption of a protein’s structure
• When a protein becomes unfolded and disorganized, they become dysfunctional
• Denaturation can be reversible
• Causes of denaturation include heat, organic solvents, mechanical mixing, and heavy metal ions

Prion Diseases

• Prion diseases are caused by the misfolding of a protein called the prion protein
• Misfolded prion proteins can convert other normal prion proteins into misfolded forms
• Misfolded prion proteins aggregate and form amyloid plaques, which can damage brain tissue

Alzheimer's Disease

• Alzheimer's disease is caused by the accumulation of amyloid-beta plaques and neurofibrillary tangles in the brain
• Amyloid-beta plaques are formed by misfolded amyloid-beta proteins
• Neurofibrillary tangles are formed by misfolded tau proteins
• Both amyloid-beta plaques and neurofibrillary tangles contribute to the death of brain cells and the symptoms of Alzheimer's disease

Explore the fundamental structures and classifications of amino acids in this quiz. Learn about the 20 essential amino acids commonly found in mammalian proteins and their various functional groups. Enhance your understanding of their roles in biological processes and diseases.