Calcitonin Amino acid sequence

N I7.49%To 22.35%. Synthetic analog of eel calcitonin amino acid sequence also similar to that of salmon calcitonin. Polypeptide hormone effective in the reduction of plasma calcium. More stable than natural calcitonins because of the absence of disulfide bridges. Prepn S. Saka-kibara et at, Ger. pat. 2,616,399 eidem, LI.S. pat. 4,086,221 (1976, 1978 both to Toyo Jozo) T. Morikawa et ah, Experientia 32, 1104 (1976). In vitro growth inhibition of human breast cancer cells Y. Iwasaki et at, Biochem. Blophys. Res. Common. 110, 235 (1983). Clinical pharmacology T, Ishi-oka, Pharmatherapeutica 1, 625 (1977). Clinical study in Paget s disease A. Caniggia er ah, Minerva Med. 74, 993 (1983) in osteoporosis Italian Osteoporosis Network, Curr, Ther. Res. 45, 502 (1989). 

Eig. 6. Amino acid sequence of human (H) and porcine (P) calcitonins. 

Calcitonin is a naturally occurring mammalian hormone that plays a major role in regulation of calcium levels. It inhibits bone resorption by binding to osteoclast receptors. Compared with mammalian calcitonin, salmon calcitonin has high potency and extended duration of action. Although commercial formulations of calcitonin-salmon actually are synthetic and not derived from salmon, they contain the same amino acid sequence as calcitonin of salmon origin. 

FIGURE 2.3 The three main families of mammalian G-protein-coupled 7TM receptors in mammals. No obvious sequence identity is found between the rhodopsin-like family A, the glucagon/VIP/calcitonin family B, and the metabotropic glutamate/chemosensor family C of G-protein-coupled 7TM receptors, with the exception of the disulfide bridge between the top of TM-III and the middle of extracellular loop-2 (see Figure 2.2). Similarly, no apparent sequence identity exists among members of these three families and, for example the 7TM bitter taste receptors, the V1R pheromone receptors, and the 7TM frizzled proteins, which all are either known or believed to be G-protein-coupled receptors. Bacteriorhodopsins, which are not G-protein-coupled proteins but proton pumps, are totally different in respect to amino-acid sequence but have a seven-helical bundle arranged rather similarly to that for the G-protein-coupled receptors. 

Calcitonin is a single-chain polypeptide composed of 32 amino acid residues having a molecular weight of approximately 3600. A cysteine disulfide bridge at the 1-7 position of the amino terminal end of the peptide is essential for biological activity however, the entire amino acid sequence is required for optimal activity. 

Amino acid sequence of human calcitonin. [Reproduced with permission from R. K. Murray, D. K. Granner, R A. Mayes, and V. W. Rodwell, Norwalk Harper s Biochemistry, 21st ed. Appleton Lange, Norwalk, 1988. 1988 Appleton Lange. ]... 

Progress in the field has been rapid. Calcitonin has been isolated from the thyroid or the ultimobranchial body in more than twenty species (F5) including man. Calcitonin was purified, and the amino acid sequence was determined (N2, P7). The molecular weight is approximately 3600. The synthesis of calcitonin was reported within the past year (B6, R7). Recent reviews on calcitonin are available (F5, M2). 

The amino acid sequences of porcine, bovine, human, and salmon calcitonin are known. That of porcine calcitonin is shown in Fig. 5-13. Studies relating structure and activity have begun, but it is too early for any definite conclusion. Of the 32 amino acids, 18 in the human calcitonin sequence differ from those in the porcine hormone, and salmon calcitonin is more active in mammals than all known mammalian calcitonins. Moreover, the effect of salmon calcitonin is much longer than that of mammalian calcitonin. 

An alternative therapeutic approach to osteoporosis is through the use of calcitonin (798), a peptide hormone containing 32 amino acids (the sequence is species dependent) secreted by the thyroid gland, which stimulates the production of new bone. Synthetic calcitonins corresponding to human, eel, and salmon variants, and natural calcitonin extracted from pig thyroid, are all used in medicine - they have slightly different efficacies, side effects, and tolerance levels (799). 

Adrenomedullin (AM) was first discovered in human adrenal medullary pheochromocytoma tissue. It is a 52-amino acid peptide with a six-amino-acid ring and a C-terminal amidation sequence. Like CGRP, AM is a member of the calcitonin family of peptides. 

Class Synthetic polypeptide hormone with the same linear sequence of amino acids as calcitonin ot salmon origin... 

The calcitonin precursor contains about 135 amino acid residues (M.W. 15,000) from which the amino and car-boxy terminal sequences are removed to yield the active peptide of 32-aminos-acid residues (M.W. 3590). Calcitonin from humans contains a disulfide bridge between amino acids 1 and 7 and a C-terminal proline amide (Figure 37-5). Salmon calcitonin, the type most frequently used clinically, is 25-100 times as potent as human calcitonin. Increased resistance to degradation and tighter binding to membrane receptors may contribute to the increased potency. 

Calcitonin is produced by the C cells of the thyroid gland its actions generally oppose those of PTH. Calcitonin is a single-chain polypeptide hormone of 32 amino acids with an intrachain disulfide bridge. Salmon calcitonin, which differs from the human sequence at approximately half of the residues, is used therapeutically because it is more potent and is cleared more slowly from the circulation. 

Hormones have recently been discovered that are likely to act on bone by either preventing resorption or facilitating deposition of calcium [29-31]. One of these hormones was found in the parathyroid gland (calcitonin), the other, in the thyroid gland (thyrocalcitonin). Thyro-calcitonin, which has been purified from pig thyroids, is a polypetide hormone with a molecular weight of 3,000 and composed of 32 amino acids (see Fig. 5-13). The intact sequence is indispensable for activity. The amino terminal segment of the molecule contains an intrachain disulfide bridge. 

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