Hultsch Christina, Hellwig Michael, Pawelke Beate, Bergmann Ralf, Rode Katrin, Pietzsch Jens, Krause René, Henle Thomas
Institute of Radiopharmacy, Research Center Rossendorf, P.O. Box 51 01 19, D-01314 Dresden, Germany.
Nucl Med Biol. 2006 Oct;33(7):865-73. doi: 10.1016/j.nucmedbio.2006.07.007.
Amadori products are formed in the early stage of the so-called Maillard reaction between reducing sugars and amino acids or proteins. Such nonenzymatic glycosylation may occur during the heating or storage of foods, but also under physiological conditions. N-epsilon-fructoselysine is formed via this reaction between the epsilon-amino group of peptide-bound lysine and glucose. Despite the fact that, in certain heated foods, up to 50% of lysyl moieties may be modified to such lysine derivatives, up to now, very little is known about the metabolic fate of alimentary administered Amadori compounds. In the present study, N-succinimidyl-4-[18F]fluorobenzoate was used to modify N-epsilon-fructoselysine at the alpha-amino group of the lysyl moiety. The in vitro stability of the resulting 4-[18F]fluorobenzoylated derivative was tested in different tissue homogenates. Furthermore, the 4-[18F]fluorobenzoylated N-epsilon-fructoselysine was used in positron emission tomography studies, as well as in studies concerning biodistribution and catabolism. The results show that the 4-[18F]fluorobenzoylated N-epsilon-fructoselysine is phosphorylated in vitro, as well as in vivo. This phosphorylation is caused by fructosamine 3-kinases and occurs in vivo, particularly in the kidneys. Despite the action of these enzymes, it was shown that a large part of the intravenously applied radiolabeled N-epsilon-fructoselysine was excreted nearly unchanged in the urine. Therefore, it was concluded that the predominant part of peptide-bound lysine that was fructosylated during food processing is not available for nutrition.
阿马多里产物是在还原糖与氨基酸或蛋白质之间所谓的美拉德反应早期形成的。这种非酶糖基化可能发生在食物加热或储存过程中，也可能在生理条件下发生。N-ε-果糖赖氨酸是通过肽结合赖氨酸的ε-氨基与葡萄糖之间的这种反应形成的。尽管在某些加热的食物中，高达50%的赖氨酰部分可能被修饰成这种赖氨酸衍生物，但到目前为止，关于经消化道给予的阿马多里化合物的代谢命运知之甚少。在本研究中，N-琥珀酰亚胺基-4-[18F]氟苯甲酸酯用于在赖氨酰部分的α-氨基处修饰N-ε-果糖赖氨酸。在不同的组织匀浆中测试了所得的4-[18F]氟苯甲酰化衍生物的体外稳定性。此外，4-[18F]氟苯甲酰化的N-ε-果糖赖氨酸用于正电子发射断层扫描研究以及生物分布和分解代谢研究。结果表明，4-[18F]氟苯甲酰化的N-ε-果糖赖氨酸在体外和体内均被磷酸化。这种磷酸化是由果糖胺3-激酶引起的，并且在体内尤其在肾脏中发生。尽管有这些酶的作用，但结果表明静脉注射的放射性标记的N-ε-果糖赖氨酸大部分几乎原样从尿液中排出。因此，得出的结论是，在食品加工过程中被果糖基化的肽结合赖氨酸的主要部分不能用于营养。
