EFFECT OF HYDROXYPENTENAL ON METABOLISM OF NORMAL AND MALIGNANT CELLS

Hydroxypentenal (4-hydroxy-2,3-trans-pentenal) strongly inhibits tricarboxylic acid cycle oxidations, glycolysis and the incorporation of radioactive precursors into DNA, RNA, protein and lipids of ascites tumor cells. It does not inhibit, however, the decarboxylation of glucose by the pentose phosphate cycle. All the observed inhibitions can be prevented by addition of GSH to the incubation medium. The inhibition of glycolysis and oxygen uptake can also be reversed by addition of CySH to aldehyde treated cells. The metabolism of cells in normal tissues (spleen, thymus, jejunum) is inhibited in similar manner, but about four times higher concentration of hydroxypentenal is necessary to obtain the same degree of inhibition as in tumor cells. High concentrations of hydroxypentenal (1 m M and more) cause cell disintegration (stalagmosis). The double bond of hydroxypentenal reacts avidly with SH groups of GSH and CySH, forming a covalent bond. By a similar reaction hydroxypentenal inhibits also the activity of crystalline glyceraldehyde-3-phosphate dehydrogenase. The latter inhibition can be reversed by high concentrations of CySH. Five other crystalline SH-enzymes, however, were not significantly affected. Nevertheless, the indications are that hydroxypentenal inhibits cell metabolism mainly by its reactions with respective SH enzymes and/or SH cofactors (CoA, lipoic acid, GSH). The relative resistance of normal cell metabolism probably may be the result of higher contents of low molecular SH-compounds, providing a better protection of functional SH-groups of enzymes. © 1969 Springer-Verlag.