Ethionine biochemical effects

Depletion of ATP is caused by many toxic compounds, and this will result in a variety of biochemical changes. Although there are many ways for toxic compounds to cause a depletion of ATP in the cell, interference with mitochondrial oxidative phosphorylation is perhaps the most common. Thus, compounds, such as 2,4-dinitrophenol, which uncouple the production of ATP from the electron transport chain, will cause such an effect, but will also cause inhibition of electron transport or depletion of NADH. Excessive use of ATP or sequestration are other mechanisms, the latter being more fully described in relation to ethionine toxicity in chapter 7. Also, DNA damage, which causes the activation of poly(ADP-ribose) polymerase (PARP), may lead to ATP depletion (see below). A lack of ATP in the cell means that active transport into, out of, and within the cell is compromised or halted, with the result that the concentration of ions such as Na+, K+, and Ca2+ in particular compartments will change. Also, various synthetic biochemical processes such as protein synthesis, gluconeogenesis, and lipid synthesis will tend to be decreased. At the tissue level, this may mean that hepatocytes do not produce bile efficiently and proximal tubules do not actively reabsorb essential amino acids and glucose. 

Shull, K. H. and S. Villa-Trevino The effects of hadacidin and inosine on hepatic protein synthesis and ATP levels in ethionine-treated rats. Biochem. Biophys. Res. Commun. 16, 101 (1964). 

Platt DS, Cockrill BL. 1969. Biochemical changes in rat liver in response to treatment with drugs and other agents. II. Effects of halothane, DDT, other chlorinated hydrocarbons, dimethyinitrosamine and ethionine. Biochem Pharmacol 18 445-457. 

Bentley, R., J. A. Ghaphery, and J. G. Keil Effect of ethionine on tropolone biosynthesis in Penicillium stipitatum. Arch. Biochem. Biophys. Ill, 80 (1965). 

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