Human growth hormone molecule

Human growth hormone is a single polypeptide chain of 191 amino acids (qv) having two disulfide bonds, one between Cys-53 and Cys-165, forming a large loop in the molecule, and the other between Cys-182 and Cys-189, forming a small loop near the C-terminus. The stmcture of hGH is shown in Figure 1 molecular mass is 22,125 the empirical formula is C qH 29N 262 300 7 ... 

Human growth hormone is a very complex molecule biologically. Several diverse biological activities such as anaboHc, insulin-like, diabetogenic, and lactogenic activities have been ascribed to hGH, which also appears to promote water and salt retention. An in-depth discussion of these activities may be found in several excellent reviews available in the Hterature (34—36). 

Figure 13.20 Ribbon diagram of the structure of a 1 2 complex between the human growth hormone and the extracellular domains of two receptor molecules. The two receptor molecules (blue) bind the hormone (red) with essentially the same loop regions (yellow).

Cunninghum BC, Ultsch M, De Vos AM, Mulkerrin MG, Clauser KR, Wells JA. Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. Science 1991 254 821-825. 

This approach appears somewhat irrational and without much scientific merit, since many of these new molecules are minimally toxic or nontoxic by this sort of acute evaluation. As in the case of interferons or monoclonal antibodies, the toxic effects observed in humans might not be predicted from safety assessments in rodents. An appropriate test species should be selected. Is the rat or mouse the appropriate species to evaluate a species-specific rDNA protein such as human growth hormone or interferons, or would nonhuman primates be more suitable Does the nonhuman primate really offer any advantages There is some consensus that the nonhuman primate may be a more appropriate species for testing some rDNA human proteins. 

Oxidation of methionine is particularly favoured under conditions of low pH, and in the presence of various metal ions. Methionine residues on the surface of a protein are obviously particularly susceptible to oxidation. Those buried internally in the protein are less accessible to oxidants. Human growth hormone (hGH) contains three methionine residues (at positions 14, 125 and 170). Studies have found that oxidation of methionine 14 and 125 (the more readily accessible ones) does not greatly effect hGH activity however, oxidation of all three methionine residues results in almost total inactivation of the molecule. 

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