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Amino acids, Peptides, and Proteins
BIOL420Çağdaş D. Son
Outline
• What are proteins?• Building blocks• Properties of Amino Acids• Uncommon Amino Acids• Reactions of Amino Acids
• Proteins are the most abundant biological macromolecules, occurring in all cells and all parts of cells.
• Proteins also occur in great variety;
• Proteins are the molecular instruments through which genetic information is expressed.
Protein Basics
Protein Basics• Proteins are biological macromolecules made
of amino acids arranged in a linear chain and folded into varius 3D structures.
• The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues
• The sequence of amino acids in a protein is defined by the sequence of a gene, which is encoded in the genetic code
Protein Basics• Proteins are polymers of amino acids, with each
amino acid residue joined to its neighbour by a specific type of covalent bond.
• An amino acid is any organic molecule with at least one carboxyl group (organic acid) and at least one amino group (organic base).
• Several hundreds of different amino acids are known to be present in plant and animal cells. Only those 20, are genetically coded for incorporation into proteins.
Amino Acids
pH = 7.4
Chirality• A chiral molecule is a type of molecule that
lacks an internal plane of symmetry and has a non-superimposable mirror image.
• The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom
• Two mirror images of a chiral molecule are called enantiomers or optical isomers
Chirality
Chirality for Amino Acids• For all the common amino acids except glycine, the α-carbon
is bonded to four different groups: a carboxyl group, an amino group, an R group, and a hydrogen atom.
• The α-carbon atom is thus a chiral center. Because of the tetrahedral arrangement of the bonding orbitals around the α-carbon atom, the four different groups can occupy two unique spatial arrangements, and thus amino acids have two possible stereoisomers.
• Since they are nonsuperimposable mirror images of each other, the two forms represent a class of stereoisomers called enantiomers. All molecules with a chiral center are also optically active—that is, they rotate plane-polarized light.
Determining the D/L isomeric form of an Amino Acid
• the "CORN" rule• The groups: COOH, R, NH2 and H (where R is a
variant carbon chain)are arranged around the chiral center carbon atom.
• Sighting with the hydrogen atom away from the viewer, if these groups are arranged clockwise around the carbon atom, then it is the D-form.
• If counter-clockwise, it is the L-form.
The D and L enantiomers for the amino acid, Alanine.
Chirality• In Biological systems L-form of the amino acids is
prefered.• D-alanine and D-glutamate are first discovered in
short peptides of cell walls of Gram-negative bacteria.• D-valine is present in peptide antibiotics:
valinomycine, actinomycin D, gramicidin A.• D-aspartate is isolated in human teeth, eye lenses,
erythrocytes and some tumors.• D-serine is isolated from mammalian brain where it
functions as neurotransmitter.
Amino Acids Can Be Classified by R Group• Nonpolar, Aliphatic R Groups The R groups in this class of
amino acids are nonpolar and hydrophobic.
• Aromatic R Groups Phenylalanine, tyrosine, and tryptophan, with their aromatic side chains, are relatively nonpolar (hydrophobic). All can participate in hydrophobic interactions. The hydroxyl group of tyrosine can form hydrogen bonds.
• Polar, Uncharged R Groups The R groups of these amino acids are more soluble in water, or more hydrophilic, than those of the nonpolar amino acids, because they contain functional groups that form hydrogen bonds with water.
Amino Acids Can Be Classified by R Group
• Positively Charged (Basic) R Groups The most hydrophilic R groups are those that are either positively or negatively charged.
• Negatively Charged (Acidic) R Groups The two amino acids having R groups with a net negative charge at pH 7.0 are aspartate and glutamate, each of which has a second carboxyl group.
Uncommon Amino Acids Also HaveImportant Functions
• In addition to the 20 common amino acids, proteins may contain residues created by modification of common residues already incorporated into a polypeptide.
• Among these uncommon amino acids are:• 6-NMethyllysine is a constituent of myosin, a contractile protein of
muscle. Another important uncommon amino acid is γ-carboxyglutamate, found in the bloodclotting protein prothrombin and in certain other proteins that bind Ca2 as part of their biological function.
• More complex is desmosine, a derivative of four Lys residues, which is found in the fibrous protein elastin.
www.ull.chemistry/uakron/biochem/04
21st amino acid
Mammalian glutathione peroxidase enzyme contains selenocysteine.
www.ull.chemistry/uakron/biochem/04
22nd amino acid
Monomethylamine methyltransferase enzyme of a freshwater bacteria contains this amino acid.
• Selenocysteine is a special case. This rare amino acid residue is introduced during protein synthesis rather than created through a postsynthetic modification. It contains selenium rather than the sulfur of cysteine. Actually derived from serine, selenocysteine is a constituent of just a few known proteins.
• Some 300 additional amino acids have been found in cells. They have a variety of functions but are not constituents of proteins.
• Ornithine and citrulline deserve special note because they are key intermediates (metabolites) in the biosynthesis of arginine and in the urea cycle.
Amino Acids Can Act as Acids and Bases• When an amino acid is dissolved in water, it exists in
solution as the dipolar ion, or zwitterion (German for “hybrid ion”). A zwitterion can act as either an acid (proton donor) or a base (proton acceptor):
• Substances having this dual nature are amphoteric and are often called ampholytes (from “amphoteric electrolytes”).
• A simple monoamino monocarboxylic α-amino acid, such as alanine, is a diprotic acid when fully protonated—it has two groups, the -COOH group and the –NH+3 group, that can yield protons.
Ionizable Groups
Titration of an amino acid
Two ionic forms of Histidine may be present in vivo. Which one would be predominant at a pH of 7.4?
pH = pKa + log ( [A-]/ [HA] )
The amino acid cysteine has an –SH (sulfhydryl) group on the side chain. This -SH group of cysteine can react under oxidizing conditions with an –SH of another cysteine forming a disulfide bond. This covalent bonding between cysteines becomes important in protein three-dimensional structures.
Two Cysteine residues react with an oxidizing agent to form Cystine containing a disulfide bond. A reducing agent AH2, causes the cleavage of the disulfide bond to reverse the reaction
Peptide Bond
Primary Structure