Hydroxylamine derivatives for regulation of spermine and spermidine metabolism

• Published in: Biochemistry (Moscow) Vol. 78; no. 13; pp. 1431 - 1446
• Main Authors: Khomutov, M. A., Weisell, J., Hyvönen, M., Keinänen, T. A., Vepsäläinen, J., Alhonen, L., Khomutov, A. R., Kochetkov, S. N.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-12-2013; Springer; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Cell culture; Cellular biology; Humans; Hydroxylamine - metabolism; Life Sciences; Metabolism; Microbiology; Ornithine decarboxylase; Ornithine Decarboxylase - metabolism; Oxidoreductases Acting on CH-NH Group Donors - metabolism; Polyamine Oxidase; Polyamines; Review; Spermidine - biosynthesis; Spermine - biosynthesis; Russia; spermidine; spermidine/spermine; cell culture; spermine; ornithine decarboxylase; adenosylmethionine decarboxylase; substituted hydroxylamines; polyamines; acetyltransferase
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297913130051

The biogenic polyamines spermine, spermidine, and their precursor putrescine are present in micro-to-millimolar concentrations in all cell types and are vitally important for their normal growth. High intracellular content of spermine and spermidine determines the multiplicity of the cellular functions of the polyamines. Many of these functions are not well characterized at the molecular level, ensuring the ongoing development of this field of biochemistry. Tumor cells have elevated polyamine level if compared with normal cells, and this greatly stimulates the search for new opportunities to deplete the intracellular pool of spermine and spermidine resulting in decrease in cell growth and even cell death.
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-Substituted hydroxylamines occupy their own place among chemical regulators of the activity of the enzymes of polyamine metabolism. Varying the structure of the alkyl substituent made it possible to obtain within one class of chemical compounds highly effective inhibitors and regulators of the activity of all the enzymes of putrescine, spermine and spermidine metabolism (with the exception of FAD-dependent spermine oxidase and acetylpolyamine oxidase), effectors of the polyamine transport system, and even actively transported in cells “proinhibitor” of ornithine decarboxylase. Some principles for the design of specific inhibitors of these enzymes as well as the peculiarities of cellular effects of corresponding
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-substituted hydroxylamines are discussed.