Naturally occurring variants

Processing of GH could go further, with production of relatively small peptides which retain substantial or even enhanced activity, and it has been suggested that this may be important in the actions of the hormone in vivo [131]. In particular, fragments which retain the diabetogenic or insulin-like activities of GH have been reported [95,131]. What role these play in the normal physiological actions of the hormone is unclear. 

Several other variants of GH have been described, particularly for the human hormone, including potentially the product of a second GH gene [132]. It remains uncertain, however, as to whether any of these has real significance or whether the normal (22K) form of GH is sufficient to explain all significant effects of the hormone, the variant forms being simply side products of little or no importance. 

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Koyano, S., Kurose, K., Saito, Y., et al. (2004) Functional characterization of four naturally occurring variants of human pregnane X receptor (PXR) one variant causes dramatic loss of both DNA binding activity and the transactivation of the CYP3A4 promoter/enhancer region. Drug Metab. Dispos. 32, 149-154. 

The substrates for capsaicinoid synthase were first defined by Fujiwake et al. [70] to be vanillylamine and 8-methyl-6-nonenoyl CoA. The synthesis of dihydrocapsaicin and the other naturally occurring variants are achieved by condensation of vanillylamine with the respective branched chain acyl, for example, 8-methylnonanoyl-CoA. The gene for capsaicinoid synthase has been linked to an acyltransferase At3 or Punl) cloned by Kim et al. [66] and mapped to the C locus on chromosome 2 [71, 72], Direct biochemical confirmation of capsaicinoid synthase remains to be established. 

Hemoglobin Variants There are almost 500 naturally occurring variants of hemoglobin. Most are the result of a single amino acid substitution in a globin polypeptide chain. Some variants produce clinical illness, though not all variants have deleterious effects. A brief sample follows ... 

Bernard, O. and Guillemette, C. (2004) The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the effect of naturally occurring variants. Drug Metabolism and Disposition The Biological Fate of Chemicals, 32, 775—778. 

A. Bossers, R. de Vries, M. A. Smits Susceptibility of sheep for scrapie as assessed by in vitro conversion of nine naturally occurring variants of PrP. Journal of Virology 74, 1407 (2000). 

M. Orho-Melander, H. Shimomura, T. Sanke, S. K. Rasmussen, K. Nanjo, O. Pederson, L. C. Groop, Expression of naturally occurring variants in the muecle glycogen synthase gene Dici-... 

Naturally occurring variants of apolipoproteins have been identified that result in specific metabolic disorders (apolipoproteinopathies). 

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