Endorphins 3-endorphin, structure

Calmodulin (CaM) undergoes drastic conformational change when it binds Ca2+ and amphiphilic peptides such as mas to po ran and endorphin, which results in the modulation of many important biochemical reactions. The N-terminal and C-terminal of rigid structured globular domains are bridged with a long flexible peptide of a-helical structure. Each domain binds two Ca2+ ions to its hydrophobic sites. 

Met-enkephalin is just one of many endorphins, which are pain-relieving polypeptides produced by the body. Studies show a similarity between the structure of opioids and the structure of the tyrosine—glycine-glycine portion of this macromolecule, a similarity that supports the notion that endorphins and opioids fit the same receptor sites. 

Figure 30-2 Schematic structure of prepro-opiomelanocortin and of some of the products of its processing by protolytic enzymes The abbreviations K and R are for lysine and arginine. a-MSH CLIP V-LPH P-endorphin...

The endorphins are a group of naturally occurring neuroproteins that act in a manner similar to morphine to control pain. Research has shown that the biologically active part of the endorphin molecule is a simple pentapeptide called an enkephalin, with the structure Tyr-Gly-Gly-Phe-Met. Draw the complete structure of this enkephalin. 

In the 1970s, researchers were able to discover exactly how morphine works in the brain. When stimulated by tiny electric currents, certain nerve tracts within the core of the brain can produce a painkiller strong enough to allow abdominal surgery in lab rodents. The painkiller consists of simple amino acids that, in their naturally folded state, mimic the structure of the morphine molecule. They were named enkephalins, for in the head, and endorphins, for the morphine within. ... 

Cyanogen bromide cleaves peptides at the carboxyl side of Met. There is only one Met in the structure (see the fifth trypsin fragment), and the cyanogen bromide cleavage gives a hexapeptide consisting of the first six amino acids of this fragment. The N-terminal amino acid must be Tyr. We now know the first ten and the last two amino acids of p-endorphin. 

Although similar in primary structure to proteins, endorphins are smaller, ranging from five to forty or more amino acids in length. Endorphins are not considered to be neurotransmitter molecules, but are instead classified as neuromodulatory, that is, they modify the action of neurotransmitters through a number of effects associated with pain or pleasure. 

Taylor, Kaiser, and their co-workers (Taylor and Kaiser, 1986) prepared a series of model peptides that were designed to test the role of each of the postulated modules in /8-endorphin. Figure 13 illustrates a-helical net diagrams of the proposed helical auxiliary sequence of /3-endorphin. The hydrophobic residues in this structure cover half the surface of the helix, twisting around the structure in a clockwise manner. [It has also been noted that if this sequence were to form a tt helix rather than an a... 

Fig. 12. Amino acid sequence and structural assignments for human /3-endorphin (Taylor and Kaiser, 1986).

The aforementioned synthetic modeling approach, which was so successfully applied to studying the structural properties of /3-endorphin, appears to be general and has been applied to the study of several other peptide hormones and hormone-releasing factors including glucagon... 

All endorphins have a common initial sequence, which corresponds to the structure of Met-enkephalin. 

The releasing hormone CRH 40, isolated as a linear peptide-amide with 41 amino acids from ovine hypothalami by Vale et al.81) in 1981, has certain structural similarities with angiotensinogen. It stimulates the secretion of corticotropin and P-endorphin. In 1985 Morell et al.82) synthesized ovine CRH by the solid-phase method. 

Endorphins are peptides produced by the intermediate pituitary that react with the brain s opioid receptors and presumably act as endogenous analgesics. The two best known endorphins from bovine brain are the pentapeptides, met-enkephalin and leu-enkephalin, whose structures are Tyr-Gly-Gly-Phe-Met and Tyr-Gly-Gly-Phe-Leu, respectively. There is evidence that the enkephalins, MSH, and ACTH are produced from the same precursor protein, pro-opiomelanocortin, molecular weight (MW) 31,000. This protein is present in both the anterior and intermediate pituitary glands. In the anterior pituitary area, this protein loses the element of ACTH (39 amino acids). In the intermediate pituitary, this protein... 

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