Chapter 3 - Proteins

Abstract

Proteins are the most abundant organic compounds in animals. They are composed of C, H, O, N, and S, and are polymers made up of amino acids (AA). Twenty different AAs are obtained after complete hydrolysis of proteins. They are classified according to the characteristics of their carbon chain. AA are dipolar molecules, containing acid and basic groups in the same molecule. Except glycine, other AA have an asymmetric C and show optical isomerism. In animals all AA are l-isomers. The carboxyl group of an AA binds to the α amine of the αC of another by a peptide bond. Peptides are AA polymers of less than 6000 kDa. Proteins are polymers more than 6000 kDa. At the pH called isoelectric point (Pi or pI), the dissociation of positive and negative groups in an AA, a peptide or a protein is the same, and the overall net charge of the molecule is zero. In a medium that is acid compared to the pI of the protein, the polypeptide has a positive charge, whereas in medium that is alkaline with respect to the protein pI, the molecule is negatively charged. Proteins can be separated based on their charge by electrophoresis. Dialysis is another method to separate proteins from small molecules in a mixture using a semipermeable membrane. The structure of proteins is complex. Primary structure refers to the order or sequence of the AA that constitute the protein. Secondary structure refers to the spatial distribution of the AA (α helix, β sheet, and random coil). Tertiary structure designates the tridimensional shape that the protein finally adopts. This is maintained by H bonds, hydrophobic or hydrophilic interactions, electrostatic forces, and disulfide bridges. Quaternary structure indicates the spatial arrangement of different subunits of a protein. Protein denaturation occurs when there is disruption of the forces that maintain the protein structure. Some proteins contain a nonprotein portion (prosthetic group). Based on their shape, proteins are classified as globular or fibrous. Examples of important proteins in the body are described in the following sentences. (1) Collagen, which constitutes the fibers of the connective tissue, is rich in glycine and proline and forms helical structures (tropocollagen) of high mechanical strength. (2) Hemoglobin (Hb), the protein that transports O2 in blood, has four polypeptide chains (HbA1, the most abundant in the adult, is a α2β2 tetramer; HbF is the form in the fetus, which contains α2γ2 subunits). Each hemoglobin subunits is associated with a tetrapyrrole ring containing Fe2+ (heme) as prosthetic group. Hb derivatives include carboxyhemoglobin, which is bound to CO and methemoglobin, with hematin, or heme containing Fe3+. Hemoglobinopathies include a series of genetic defects in which Hb is abnormal (i.e., HbS in sickle cell disease and thalasemia). (3) Plasma proteins circulate in the bloodstream at a concentration of 6–8 g/dL. Several fractions can be demonstrated in plasma by electrophoretic separation; these are albumin and α1, α2, β, and γ globulins. Albumin is the most abundant plasma protein fraction (3.5–4.0 g/dL). It is a globular protein, which carries fatty acids, bile pigments, steroids, hormones, and drugs in blood. Lipoproteins are carriers of lipids in plasma. They exist as four different groups [chylomicrons, very low density lipoproteins (VLDLs), low density lipoproteins (LDLs), and high density lipoproteins (HDLs)]. (4) Muscle proteins include myosin, actin, tropomyosin, and troponin. Myosin thick filaments form the A band of the sarcomere. They have globular heads protruding from the filaments as side arms and possess ATPase activity. G-actin polymerizes as F actin to form thin filaments. Tropomyosin and troponin associate with F-actin. These proteins are involved in muscle contraction; the shortening of the muscle fibers is produced by the sliding of fine filaments between the thick filaments.