Hormones polypeptide based

A wide range of pharmaceutical substances are derived from animal sources (Table 1.10). Many are protein-based and detailed description of products such as insulin and other polypeptide hormones, antibody preparations, vaccines, enzymes, etc., have been deferred to subsequent chapters. (Many of the therapeutic proteins are now also produced by recombinant DNA technology. Considerable overlap would have been generated had a product obtained by direct extraction from native sources been discussed here, with further discussion of a version of the same product produced by recombinant DNA technology at a later stage.) Non-proteinaceous pharmaceuticals originally derived from animal sources include steroid (sex) hormones, corticosteroids and prostaglandins. A limited discussion of these substances is presented below, as they will not be discussed in subsequent chapters. Most of these substances are now prepared synthetically. 

Only recently was the first higfr-resolution atomic structure of a G-protein-coupled receptor solved, namely that of rhodopsin, although lower-resolution spatial structural information based on two-dimensional crystals and electron diffraction and NMR structures was available.3.4 This information makes it certain that all heptahelical receptors have the same topological arrangement of the polypeptide chains. The amino- and carboxy-termini are oriented in the same way, with the amino-terminus outside and carboxy-terminus on the cytoplasmic side. Valuable structural relationships between different G-protein-coupled receptors for hormones have also come to light, mainly thanks to comparisons of cDNA-derived sequences. ... 

The antidiuretic hormone is secreted according to a first-order neuroendocrine mechanism. A central nervous system neuron secretes the active polypeptide, which is transported in the blood to the target organ. This assumption is based on the experiments of Horsley and Clarke, who destroyed the hypothalamic nuclei without affecting the hypophysis itself by approaching the thalamus from above. These experiments demonstrated that destruction of the supraoptic nuclei or of the fiber tracts that lead from these nuclei to the posterior lobe was consistently associated with diabetes insipidus. In contrast, total hypophysectomy does not necessarily induce diabetes insipidus. 

Table II represents the author s estimate of the physiological significance of the in vitro findings with hormones reported in the literature, as based upon the above criteria. It will be seen that a sizable number of hormones exert in vitro effects which are comparable in their essentials to the physiological effects observed in vivo. Among these are seen all chemical classes of hormones with the exception of the steroids protein— insulin polypeptides—ACTH, antidiuretic hormone (ADH), oxytocin, and glucagon or hyperglycemic factor (HGF) and amino acid derivatives —epinephrine and nor-epinephrine. The remaining hormones listed, in which physiologically meaningful in vitro results have not been as yet achieved, may be subdivided into two groups one, wherein little work has been attempted (as with parathormone, prolactin, etc.) the other, wherein extensive in vitro studies have been carried out.

The strategy for the determination of the amino acid sequence of any protein is given in Figure 4.8. It is based upon the pioneer work of Frederick Sanger, who, in 1953, successfully elucidated the primary structure of the 51-residue polypeptide hormone, insulin. A prerequisite of any sequence analysis is that a pure sample of protein has been prepared. 

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