Liver aldehyde dehydrogenase

Mitchell, D.Y. and D.R. Petersen. 1988. Inhibition of rat liver aldehyde dehydrogenases by acrolein. Drug Metabol. Dispos. 16 37 42. 

R. I. Feldman, H. Weiner, Horse Liver Aldehyde Dehydrogenase. II. Kinetics and Mechanistic Implications of Dehydrogenase and Esterase Activity , J. Biol. Chem. 1972, 247, 267-272. 

F. M. Dickinson, G. W. Haywood, The Effects of Mg2+ on Certain Steps in the Mechanism of the Dehydrogenase and Esterase Reactions Catalysed by Sheep Liver Aldehyde Dehydrogenase. Support for the View That Dehydrogenase and Esterase Activities Occur at the Same Site on the Enzyme , Biochem. J. 1986, 233, 877-883. 

Rikans LE. 1987. The oxidation of acrolein by rat liver aldehyde dehydrogenases. Relation to allyl alcohol hepatotoxicity. Drug Metab Dispos 15 356-362. 

In addition to liver aldehyde dehydrogenase, a number of other enzymes present in the soluble fraction of liver homogenates will oxidize aldehydes and certain N-heterocyclic compounds. Among these are aldehyde oxidase and xanthine oxidase (see below), both flavoprotein enzymes containing molybdenum. These enzymes catalyze the oxidation of aldehydes formed by the deamination of endogenous amines by amine oxidases. 

Coprine, isolated from the Coprinus atramentarius mushroom, and identified as hydroxycyclopropyO-L-glutamine ", 135, is the first example of a natural product containing a cyclopropanone equivalent. Coprine inhibits mouse liver aldehyde dehydrogenase in vivo but not in vitro Cyclopropanone hydrate (170), which can be derived from coprine by hydrolysis to 169 (equation 39), inhibits the enzyme both in vivo and in vitro. Cyclopropanone hydrate has thus been proposed as a metabolite of coprine which is the active agent causing the toxic effects ... 

Formic acid can be readily absorbed from the digestive tract and the respiratory system. Systemic absorption produces acidosis, neuropathy, and visual and mental disturbances. Acidosis can also be produced when formic acid is produced by liver aldehyde dehydrogenase from formaldehyde. Formaldehyde in turn can also be produced metabolically by alcohol dehydrogenase from methanol. Formic acid is oxidized to carbon dioxide by the folate-dependent pathway. Some formic acid is excreted unchanged in the urine. 

Poisoning with mushrooms in this group occurs when ethanol is consumed shortly before or within 5 days after eating the mushrooms. Coprine (N(5)-(l-hydroxy cyclopropyl)-L-glutamine) is the active constituent in these mushrooms and has been shown to inhibit liver aldehyde dehydrogenase. The active metabolite, cyclopropanone hydrate, has also been shown to possess similar activity. This inhibition of ethanol metabolism at the point of aldehyde dehydrogenase results in accumulation of acetaldehyde. In the absence of concurrent ethanol consumption, these mushrooms are edible. 

Lindros. K.O. et at. (1995) Phenethyl isothiocyanate, a new dietary liver aldehyde dehydrogenase inhibitor. J. Pharmacol. Exp. Then. 275.79-83. 

Rashkovetsky LG, MaretW, KlyosovAA (1994) Human liver aldehyde dehydrogenases new method of purification of the major mitochondrial and cytosolic enzymes and re-evaluation of their kinetic properties. Biochim Biophys Acta 1205 301-307... 

Feldman RI and Weiner H (1972) Horse liver aldehyde dehydrogenase. I. Purification and characterizations. J Biol Chem 247 260 - 266. 

Though the symptoms of the biological action of coprine and disulhram are similar, it was demonstrated that the mechanisms of action are different. Contrary to cyclopropanone hydrate, coprine inhibits mouse liver aldehyde dehydrogenase only in vivo but not in vitro. Based on this observation Wiseman and Abeles (429) assumed that coprine itself is inactive in vivo but is activated by hydrolysis to give initially cyclopropanone hemia-minal and ultimately cyclopropanone hydrate. After enzymatic dehydration to cyclopropanone, this compound forms a kinetically stable thiohe-miketal with the enzyme active-site thiols, leading to inactivation of aldehyde dehydrogenase in the enzyme-catalyzed oxidation of acetaldehyde to acetic acid (Scheme 97). 

Coprine was isolated as the agent responsible for the toxicity displayed by the mushroom Coprinus atramentarius when ingested together with ethanol (94, 202). Coprine has no effect on liver aldehyde dehydrogenase... 

Although acetaldehyde Is detectable In human and rodent blood after treatment with calcium carblmlde and alcohol39 vitro inhibition of rabbit or bovine liver aldehyde dehydrogenase can not be demonstrated, despite an earlier claim to the contrary. Livers from rabbits treated with qranamlde do show a notable decrease In ability to oxidize Indoleaeetaldehyde. A metabolic product of cyanamlde may be the... 

Lee M-0, Manthey CL, Sladek NE (1991) Identification of mouse liver aldehyde dehydrogenases that catalyze the oxidation of retinaldehyde to retinoic acid. Biochem Pharmacol 42 1279-1285 McCaffery P, Lee M-O, Wagner MA, Sladek NE, Drager UC (1992) Asymmetrical retinoic acid synthesis in the dorso-ventral axis of the retina. Development 115 371-382... 

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