Principles of Biochemistry, Volume 1 - A. Lehninger 1985

Biomolecules
Water
Certain peptides exhibit high biological activity

Aside from Peptides formed by the partial Hydrolysis of protein molecules, many peptides occur naturally in living organisms as free compounds independent of protein structures. It is particularly interesting that numerous free peptides exhibit high biological activity. For instance, A number of Hormones belong to the Class of peptides or Polypeptides. Hormones act as chemical messengers produced by specialized secretory Cells in Endocrine glands—such as the Pancreas, Pituitary Gland, and Adrenal Glands; they are transported via the bloodstream to other Tissues or Organs to regulate their specific Functions. The hormone Insulin, produced by the ß-Cells of the pancreas, enters the bloodstream and travels to various organs, notably The Liver and Muscles, where it binds to Cell-surface receptors and stimulates the uptake of glucose to be used as metabolic fuel. Insulin consists of two polypeptide chains, one containing 30 amino acid residues and the other 21. Polypeptide hormones also include another pancreatic hormone, Glucagon, which acts as an insulin antagonist, and corticotropin, produced by the anterior pituitary, which stimulates adrenal function. Corticotropin consists of 39 amino acid residues.

The molecules of certain hormones are considerably shorter peptide chains. These include oxytocin (nine amino acid residues), a hormone synthesized in the posterior pituitary that stimulates uterine contractions; bradykinin (nine residues), a peptide involved in moderating inflammatory responses in tissues; and thyrotropin-releasing hormone (three residues), synthesized in the Hypothalamus to stimulate The production of another hormone, thyrotropin (thyroid-stimulating hormone), which is secreted by the anterior pituitary (Fig. 5-23). Worthy of special mention are enkephalins—short peptides synthesized in the Central Nervous system. The binding of enkephalins to specific receptors on certain Brain cells induces analgesia, or the suppression of pain. Enkephalins (meaning "in the HEAD") are endogenous opiates produced by the body itself; they bind to the same brain sites as morphine, heroin, and other narcotic substances. Peptides also include several highly toxic poisons found in mushrooms, such as amanitin, as well as many Antibiotics, which can be viewed as a form of "chemical warfare" produced by certain microorganisms to inhibit or destroy others.

Fig. 5-23. Selected naturally occurring peptides with high biological activity. Amino-terminal residues are on the left. A. Bradykinin, a hormone-like peptide with anti-inflammatory activity. B. Oxytocin, a hormone produced in the posterior pituitary. The colored Background highlights the glycinamide residue (NH₂CH₂CONH₂). C. Thyrotropin-releasing hormone, a hormone produced in the hypothalamus. D. Enkephalins, brain peptides with opiate-like activity. E. Gramicidin S, an antibiotic.

Arrows indicate the direction from the amino-terminal to the carboxyl-terminal residue. Orn designates Ornithine, an amino acid not found in Proteins. Note that gramicidin S contains two D-amino acid residues.

It is especially remarkable that all these peptides, exerting such profound biological effects, are composed of Amino Acids that individually are completely harmless, nontoxic compounds. This clearly demonstrates that the biological activity and functional Specificity of peptides and polypeptides are determined entirely by The sequence of their constituent amino acid residues.