World of the Body: peptides
peptides are short chains of amino acids linked together. If there are only two amino acids then the peptide is a dipeptide. Similarly there are tripeptides, tetrapeptides, and so on. If the number of amino acids in the chain reaches around ten or so, such substances are called polypeptides, while large polypeptides are called proteins. There is no particular agreed size at which a large polypeptide becomes a small protein, but generally polypeptides have molecular weights of a few thousand, while proteins have molecular weights of tens of thousands. Depending on which amino acids are involved, between seven and ten amino acids will add about 1000 to the molecular weight.
Protein molecules in the diet are digested by enzymes (which are themselves specialized proteins), that break them down into smaller and smaller lengths, the breakage occurring at the peptide bonds. peptides and amino acids are thus the final cleavage products of protein digestion. Amino acids are the main protein breakdown product absorbed from the gut, but some di- and tri-peptides are also absorbed, there being specific carrier systems in the cells lining the small intestine to transport these small peptides from the lumen to the blood.
The dipeptide carnosine, formed from the amino acids alanine and histidine, was identified in muscle a century ago, but only recently has research revealed its properties and the likely variety and significance of its functions. It is known to be present also in the brain, where it may act as a neurotransmitter. In muscle it is likely to be important in making the contractile filaments more sensitive to calcium ions and in controlling the internal acidity of these fibres. It has been suggested that it may also be a scavenger of free radicals. Its strong binding with zinc may be important in co-absorption from the gut of this essential trace element; and physiologically significant interactions between carnosine, zinc, and histamine are being discovered.
The tripeptide glutathione (glutamic acid-cysteine-glycine) is an important co-factor for many enzymes, increasing their activity.
Polypeptides control or trigger a great many bodily functions, acting close to or at a distance from the site at which they are produced and released. The table below gives a few examples, giving the site of production, the number of amino acids, and an indication of the functions that the polypeptides promote.
Amino acids Origin Action
Oxytocin 9 Posterior pituitary Uterine contraction and milk ejection
Vasopressin 9 Posterior pituitary Antidiuretic (water-retaining) action in kidneys
Glucagon 29 Endocrine pancreas Increases blood sugar
ACTH 39 Anterior pituitary Stimulates release of cortisol from adrenal glands
Gastrin 17 Stomach lining Stimulates gastric acid secretion
Angiotensin 8 From precursor in Regulation of body fluid volume and the blood circulation
Bradykinin 9 In tissues Dilates blood vessels, stimulates secretions
Endothelin 21 Endothelium Constricts blood vessels
CRF 41 Hypothalamus and Promotes release of pituitary and other
many other brain hormones, and stimulates sympathetic
regions nervous activity
Substance P 11 Nervous system, gut, Vasodilator; neurotransmitter involved in
inflamed tissue pain sensation
CCK 33 Duodenal lining; As hormone, stimulates gall bladder
peripheral nerves and contraction and pancreatic secretion;
many brain regions neurotransmitter in brain
Proteins usually fold to form particular three-dimensional shapes (which determine their actions), but polypeptides are not so structurally constrained, so in solution they can adopt many conformations. For example, oxytocin and vasopressin have about a thousand different conformations in solution, all in dynamic equilibrium one with another. How is it therefore that they specifically attach to their receptors, with the requirements for specific shape and charge distribution? The answer is that some part of the polypeptide attaches to the receptor, while adjacent parts turn and rotate until the correct shape is reached. Thus the polypeptides use a ‘zipper’ mechanism to attach to membrane receptors.
There are many different peptides in neurons, released along with other neurotransmitters. Some peptides that were originally identified as hormones, thought to be produced at one particular site and to act at certain ‘target’ sites, have more recently been found to be made elsewhere also, and to have other functions. The body utilizes the same peptide for different purposes. This is true, for example, of cholecystokinin (CCK), a 33-amino-acid polypeptide that was known for many decades as a hormone that originated in the duodenum and caused emptying of the gall bladder. Since the 1980s it has been revealed to be a modulator of neural activity, produced by many nerve cells, widespread in the nervous system. Likewise, corticotrophin releasing factor (CRF), with 41 amino acids, was originally known to be made and released by a group of neurons in the hypothalamus, passing to the pituitary gland and there stimulating the secretion of ACTH (adrenocorticotrophic hormone). But it too has been found to be a neuromodulator produced by neurons in many parts of the brain.
A family of peptides called opioid peptides or endorphins, found in the brain and elsewhere in the body, are responsible for the modulation of pain sensation. One group of these, the pentapeptide enkephalins, are released as neurotransmitters by nerve cells in certain parts of the brain and spinal cord. They bind to opiate receptors (the membrane receptors on which opiate drugs act) on other nerve cells in the pathways that mediate pain, hence acting as ‘endogenous’ (internally generated) analgesics