The Other Side of Metabolism: a Review

A. G. Golubev¹

¹Institute of Experimental Medicine, Russian Academy of Medical Sciences, ul. Akademika Pavlova 12, St. Petersburg, 197476 Russia; fax: (7-812) 234-94-89.

Submitted June 19, 1996.

Since the discovery of enzymic fermentation by Louis Pasteur, the idea has been widespread in biochemistry that molecular interconversions and interactions in living systems are mediated by enzymes. However, recent advances in sensitivity and separation power of analytical methods has led to isolation and identification of a variety of products that cannot be mapped to specific enzyme-catalyzed biochemical pathways. These products appear in the organism because chemical characteristics of biomolecules are not limited to the needs of living systems realized through enzyme-catalyzed processes. This review provides a summary of such nonenzymic interactions. The following are discussed: 1) products of biogenic amine binding to carbonyl-containing compounds in the Pictet-Spengler reaction (endogenous neurotoxins, which impair mitochondrial functions and seem to contribute to development of age-related neurological disorders including parkinsonism); 2) products of Schiff base formation with subsequent Amadori rearrangement (nonenzymic protein glycation involved in age-related diabetes-like disorders and atherosclerosis; 3) products of Michael addition of methylglyoxal, 4-hydroxynonenal, and other derivatives of nonenzymic conversions of carbohydrates and lipids; 4) products of modification of biomolecules with nitrogen- and oxygen-derived free radicals, which contribute to cancer and aging. Some evolutionary and biomedical implications of nonenzymic parametabolic processes are discussed.

KEY WORDS: metabolism, nonenzymic reactions, biogenic amines, carbohydrates, lipids, free radicals.

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