Hormones polypeptide

Milk residue studies demonstrated that use of recombinantly derived somatotropin, even at exaggerated doses, did not lead to concentrations of bovine somatotropin in milk above those normally present in the untreated cows (0.9-1.6 ppb) (52, 53). Bovine somatotropin occurs naturally in cow milk at variable levels generally less than 2 ppb, but they may occasionally range up to 10 ppb. 

In regard to tissue residue data, recombinantly derived somatotropin treatment of cows leads, at most, to a doubling of bovine somatotropin concentrations to levels of 4.2 ppb in muscle and 25 ppb in liver. Cows treated with recombinantly derived somatotropin further show an up to doubling in IGF-I levels in muscle and liver. 

Porcine somatotropin and poultry somatotropin are both under development for use in swine and poultry. Recombinantly produced porcine somatotropin has been found to enhance performance dramatically. Increases in protein deposition, decreases in fat deposition, and depression of voluntary feed intake after injections of recombinant porcine somatotropin have been found across breeds. 

World Health Organization, in Residues of Some Veterinary Drugs in Animals and Foods, Thirty-second Meeting of the Joint FAOAVHO Expert Committee on Food Additives, Food and Agriculture Organization of the United Nations, FAO Food and Nutrition Paper, Rome, p. 18 (1987). 

in Environmental Quality and Safety, Anabolic Agents in Animal Production, Suppl. Vol. V (F. Coulston, and F. Corte, Eds.), Thime, Stuttgart, p. 159 (1976). A.G. Rico, V. Burgat-Sacaze, J.P. Brown, and P. Bernard, in Anabolic Agents in Beef Veal Production, Proc. EEC-Workshop, Brussels, p. 45 (1981). 

The biological basis for interleukin-1 was review by Dinarello (1996) giving 586 references. 

Three members of the interleukin-1 family have been cloned (Dinarello 1996). All bind both types of receptors but only IL-la and IL-ip (encoded on chromosome 2) are agonists. The third is the interleukin 1 receptor antagonist protein (IRAP). All share 20-25 % amino acid homology. Mature IL-la and IL-ip have similar three-dimensional open barrel structures of P sheets. 

Although several different proteinases can cleave the IL-ip precursor in vitro, the natural cleavage of the IL-ip precursor in macrophages and monocytes occurs via the action of a novel cysteine proteinase designated the IL-ip-converting enzyme. 

There are two IL-1 receptors, the type I receptor transduces a signal, whereas the type II receptor binds IL-1 but does not transduce a signal. In fact, IL-1 receptor II acts as a sink for IL-1 (3 and has been termed a decoy receptor, which is somewhat unique to cytokine biology (Colotta et al. 1994). When IL-1 binds to IL-1 receptor I, a complex is formed that then binds to the IL-1 receptor accessory protein, resulting in high-affinity binding (Greenfeder et al. 1995). 

An IL-1 receptor antagonist (IRAP) has been isolated and purified from activated monocytes. IRAP inhibits IL-1 bio activity by binding competitively at the IL-1 receptor (Eisenberg et al. 1990, Hannum et al. 1990, Mazzei et al. 1990). In vitro IRAP can attenuate IL-1-dependent fibroblast proliferation, collagenase synthesis, and prostaglandin E2 release (Hannum et al. 1990). IRAP suppressed IL-l-induced monocyte production of IL-1, tumour necrosis factor-a, or interleukin 6. Multiple hpid oxidation products in low density lipoproteins induce IL-ip release from human blood mononuclear cells (Thomas et al. 1994). 

---

Biosynthetic Human Insulin from E. coli. Insulin [9004-10-8] a polypeptide hormone, stimulates anaboHc reactions for carbohydrates, proteins, and fats thereby producing a lowered blood glucose level. Porcine insulin [12584-58-6] and bovine insulin [11070-73-8] were used to treat diabetes prior to the availabiHty of human insulin [11061 -68-0]. AH three insulins are similar in amino acid sequence. EH LiHy s human insulin was approved for testing in humans in 1980 by the U.S. EDA and was placed on the market by 1982 (11,12). 

Polypeptide hormones are synthesized as part of a larger precursor molecule or prohormone. Cleavage of the prohormone by specific cellular enzymes, ie, peptidases, produces the secreted form of the hormone. In some cases, multiple bioactive hormones are produced from a single prohormone. 

CeUs synthesize and secrete multiple hormones. Eor example, some ceUs in the anterior pituitary have the capacity to secrete both polypeptide hormones, ESH and LH. CeUs also can secrete different chemical classes of hormone, eg, ceUs in the adrenal meduUa synthesize and secrete the... 

Nontraditional Hormones. Novel hormones identified ia cardiovascular tissue have profound effects on maintenance of blood pressure and blood volume ia mammals. Atrial natriuretic hormone (ANH) is a polypeptide hormone secreted from the atria of the heart. When the cardiac atrium is stretched by increased blood volume, secretion of ANH is stimulated ANH ia turn increases salt and water excretion and reduces blood pressure (6). Endothelin is a polypeptide hormone secreted by endothehal cells throughout the vasculature. Although endothelin is released into the circulation, it acts locally in a paracrine fashion to constrict adjacent vascular smooth muscle and increase blood pressure (7). 

The G-proteins are heterotrimers made of three families of subunits, a, P, and y, which can interact specifically with discrete regions on G-protein-coupled receptors. This includes most receptors for neurotransmitters and polypeptide hormones (see Neuroregulators). G-protein-coupled receptors also embrace the odorant receptor family and the rhodopsin-linked visual cascade. 

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

V. du Vigneaud (New York) biochemically important sulfur compounds, especially the first synthesis of a polypeptide hormone. 

Chemical Name Complex polypeptide hormone with molecular weight over 6,000 see Structural Formula... 

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

Thirty years ago, receptors for polypeptide hormones such as insulin and GH were identified as binding activity in cells, membranes, or solubihzed membrane proteins using radiolabeled proteins... 

S.M. Hsu, L. Raine, and H. Fanger, A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am. J. Clin. Pathol 75, 734-738 (1981). 

Phosphorylation Influences/regulates biological activity of various polypeptide hormones... 

Although all cytokines are polypeptide regulatory factors, not all polypeptide regulatory factors are classified as cytokines. Classical polypeptide hormones, such as insulin, FSH and GH are not considered members of the cytokine family. The distinguishing features between these two groups is ill defined, and in many ways artificial. Originally, one obvious distinguishing feature was that hormones... 

Calcitonin is a polypeptide hormone that (along with PTH and the vitamin D derivative, 1,25-dihydroxycholecalciferol) plays a central role in regulating serum ionized calcium (Ca2+) and inorganic phosphate (Pi) levels. The adult human body contains up to 2 kg of calcium, of which 98 per cent is present in the skeleton (i.e. bone). Up to 85 per cent of the 1 kg of phosphorus present in the body is also found in the skeleton (the so-called mineral fraction of bone is largely composed of Ca3(P04)2, which acts as a body reservoir for both calcium and phosphorus). Calcium concentrations in human serum approximate to 0.1 mg ml-1 and are regulated very tightly (serum phosphate levels are more variable). 

A prime example of a Refolding model is that of the insulin protofilament (Jimenez et al., 2002). Insulin is a polypeptide hormone composed of two peptide chains of mainly o -helical secondary structure (Fig. 3A Adams et al., 1969). Its chains (21- and 30-amino acids long) are held together by 3 disulfide bonds, 2 interchain and 1 intrachain (Sanger, 1959). These bonds remain intact in the insulin amyloid fibrils of patients with injection amyloidosis (Dische et al., 1988). Fourier transform infrared (FTIR) and circular dichroic (CD) spectroscopy indicate that a conversion to jS-structure accompanies insulin fibril formation (Bouchard et al., 2000). The fibrils also give a cross-jS diffraction pattern (Burke and Rougvie, 1972). 

Figure 10.10 Amino acid sequence of human adrenocorticotrophin. The amino acid residues in this polypeptide hormone are linked by peptide bonds and each residue is given a number starting with the N-terminal residue (number 1) to the C-terminal residue (number 39).

The amino group of the N-terminal amino acid residue of a peptide will react with the FDNB reagent to form the characteristic yellow DNP derivative, which may be released from the peptide by either acid or enzymic hydrolysis of the peptide bond and subsequently identified. This is of historic interest because Dr F. Sanger first used this reaction in his work on the determination of the primary structure of the polypeptide hormone insulin and the reagent is often referred to as Sanger s reagent. 

Insulin is produced in the pancreas by j8 cells in the region called the islets of Langerhans. It is a polypeptide hormone consisting of two chains an A chain... 

Either fluorescent EGF or its fluorescent receptor (GFP-EGFR) can be used to track the clathrin pathway (110). Following internalization, EGF is mainly targeted to early endosomes, then to lysosomes, and following this is subsequently degraded. After a 10-minute incubation period with EGF, the polypeptide hormone accumulates in early endosomes, and after 60 to 90 minutes, EGF... 

Adiponectin a polypeptide hormone produced and released from adipose tissue that acts to increase insulin sensitivity. 

Choiecystokinin a gut-derived polypeptide hormone released in response to a food load that decreases food intake. 

Glucagon a polypeptide hormone that signals the liver to produce glucose. 

Vincent Du Vigneaud United States sulfur compounds of biological importance, synthesis of polypeptide hormone... 

Somatomedins are insulin-like polypeptide hormones that should be used with caution in diabetic patients since adjustment of antidiabetic therapy may be required. Before initiating therapy, a baseline ECG is recommended and, if abnormalities are identified, regular ECG monitoring during treatment is required. Somatomedins may cause tachycardia, cardiomegaly, ventricular hypertrophy and changes in blood glucose levels as side-effects. 

---