Biochemistry - Chemical Reactions in Living Cells, Volume 1 - D. Metzler 1980

The Molecules We Are Made Of
Proteins
Polypeptides

The sequence in which monomer units are linked together during the polymerization of 100 or more Amino Acids constitutes the Introduction/19.html">Primary Structure of Proteins. These monomer units are referred to as amino acid residues, as each amino acid loses a molecule of H₂O¹ in the course of polymerization. A polypeptide chain typically has one free amino group at one end and a free carboxyl group at the other. Occasionally, however, these groups react with each other, resulting in The formation of a cyclic peptide. Peptides are named according to their constituent amino acid residues, starting from the residue bearing the N-terminal amino group. For instance, L-alanyl-L-valyl-L-Methionine is a peptide with the following structure:

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¹ Strictly speaking, one Water molecule is lost per peptide bond; thus, the total number of water molecules lost is one less than the number of amino acid residues.

FIG. 2-1. Complete Amino Acid Sequence of cytoplasmic aspartate aminotransferase from pig Heart. Polypeptide composition: Lys_19, His₈, Arg₂₆, (Asp+Asn)₄₂, Thr₂₆, (Glu+Gln)₄₁, Pro₂₄, Gly₂₈, Ala₃₂, Cys₅, Val₂₉, Met₆, Ile₁₉, Leu₃₈, Tyr₁₂, Phe₂₃, Trp₉. The Molecular Weight of a single chain is 46,344. The holoenzyme molecule is a dimer with a molecular weight of 93,147. It contains 2 molecules of protein-bound coenzyme Pyridoxal phosphate (Chapter 8, Section D) attached to a Lysine residue, which is boxed in the figure. (Ovchinnikov Yu. et al., FEBS Lett., 29, 31–33, 1973; Doonan S. et al., FEBS Lett., 38, 229–233, 1974.)

Note that this tripeptide, like every amino acid, exists as a zwitterion. The same structure can be written in abbreviated form as Ala-Val-Met. In this notation, the N-terminal amino acid residue is placed on the left and the C-terminal residue on the right.

Recall that the Amino acid sequences in protein chains are always genetically predetermined. Knowing The amino acid sequence is essential for understanding The behavior of specific proteins. For this reason, the efforts of many biochemists in recent years have been directed toward determining the sequences of hundreds of proteins. One major protein for which this task has been accomplished is human γ-globulin, which contains 446 residues in one chain and 214 in the other. The complete amino acid sequence of another protein is shown in Fig. 2-1. Fig. 2-2 presents the sequences of several small Peptide Hormones and Antibiotics.

FIG. 2-2. Structure of several naturally occurring peptides. Oxytocin and vasopressin are Hormones of the neurohypophysis (posterior pituitary); adrenocorticotropin is a hormone of the adenohypophysis (anterior pituitary). Adenohypophyseal hormones are released in response to specific releasing factors synthesized in the Hypothalamus following neural stimulation. The structure of two such releasing factors is shown here. Note that the carboxyl groups of the N-terminal glutamates react with the adjacent terminal —NH₂ group to form cyclic amide (pyroglutamyl) groups. (Guillemin R., Burgus R., Sci. Am., 227, 24–33, Nov. 1972.) Gramicidin S is an antibiotic synthesized by the bacterium Bacillus brevis. Surfactin is a depsipeptide (containing an ester bond); it is a surface-active antibiotic synthesized by the bacterium Bacillus subtilis. (Hochster R. M., Kates M., Quastel J. H., eds., Metabolic Inhibitors, Vol. 3, p. 312, Academic Press, New York, 1973.)