Amino Acids
All peptides and polypeptides are polymers of α-amino acids. There are 20 α-amino acids that are relevant to the make-up of mammalian proteins (see below). Several other amino acids are found in the body free or in combined states (i.e. not associated with peptides or proteins). These non-protein associated amino acids perform specialized functions. Several of the amino acids found in proteins also serve functions distinct from the formation of peptides and proteins, e.g., tyrosine in the formation of thyroid hormones or glutamate acting as a neurotransmitter.
The α-amino acids in peptides and proteins (excluding proline) consist of a carboxylic acid (–COOH) and an amino (–NH2) functional group attached to the same tetrahedral carbon atom. This carbon is the α-carbon. Distinct R-groups, that distinguish one amino acid from another, also are attached to the alpha-carbon (except in the case of glycine where the R-group is hydrogen). The fourth substitution on the tetrahedral α-carbon of amino acids is hydrogen.
Amino Acid Classifications
Each of the 20 α-amino acids found in proteins can be distinguished by the R-group substitution on the α-carbon atom. There are two broad classes of amino acids based upon whether the R-group is hydrophobic or hydrophilic.
The hydrophobic amino acids tend to repel the aqueous environment and, therefore, reside predominantly in the interior of proteins. This class of amino acids does not ionize nor participate in the formation of H-bonds. The hydrophilic amino acids tend to interact with the aqueous environment, are often involved in the formation of H-bonds and are predominantly found on the exterior surfaces proteins or in the reactive centers of enzymes.
The Peptide Bond Peptide bond formation is a condensation reaction leading to the polymerization of amino acids into peptides and proteins. Peptides are small consisting of few amino acids. A number of hormones and neurotransmitters are peptides. Additionally, several antibiotics and antitumor agents are peptides.
Proteins are polypeptides of greatly divergent length. The simplest peptide, a dipeptide, contains a single peptide bond formed by the condensation of the carboxyl group of one amino acid with the amino group of the second with the concomitant elimination of water.
The presence of the carbonyl group in a peptide bond allows electron resonance stabilization to occur such that the peptide bond exhibits rigidity not unlike the typical –C=C– double bond. The peptide bond is, therefore, said to have partial double-bond character.
Acid-Base Properties of the Amino Acids The α-COOH and α-NH2 groups in amino acids are capable of ionizing (as are the acidic and basic R-groups of the amino acids). As a result of their ionizability the following ionic equilibrium reactions may be written:
R-COOH <——> R-COO– + H+
R-NH3+ <——> R-NH2 + H+
The equilibrium reactions, as written, demonstrate that amino acids contain at least two weakly acidic groups. However, the carboxyl group is a far stronger acid than the amino group. At physiological pH (around 7.4) the carboxyl group will be unprotonated and the amino group will be protonated. An amino acid with no ionizable R-group would be electrically neutral at this pH. This species is termed a zwitterion.
Like typical organic acids, the acidic strength of the carboxyl, amino and ionizable R-groups in amino acids can be defined by the association constant, Ka or more commonly the negative logrithm of Ka, the pKa. The net charge (the algebraic sum of all the charged groups present) of any amino acid, peptide or protein, will depend upon the pH of the surrounding aqueous environment.
As the pH of a solution of an amino acid or protein changes so too does the net charge. This phenomenon can be observed during the titration of any amino acid or protein. When the net charge of an amino acid or protein is zero the pH will be equivalent to the isoelectric point: pI.
Biological molecules that are insoluble in aqueous solution and soluble in organic solvents are classified as lipids. Lipids in biological systems include fats, sterols, fat soluble vitamins, phospholipids, and triglycerides. The lipids of physiological importance for humans exert the following major functions:
1. They serve as structural components of biological membranes.
2. They provide energy reserves, predominantly in the form of triglycerides (TGs; also called triacyglycerols, TAGs).
3. Lipids and lipid derivatives serve as biologically active molecules exerting a wide range of functions.
4. Lipophilic bile acids aid in emulsification, digestion and absorption of dietary lipids as well as being a form of bioactive lipids.