Aldehyde dehydrogenase and

Tsukamoto N, Chen J, Yoshida A. Enhanced expressions of glucose-6-phos-phate dehydrogenase and cytosolic aldehyde dehydrogenase and elevation of reduced glutathione level in cyclophosphamide-resistant human leukemia cells. Blood Cells Mol Dis 1998 24 231-238. 

FIGURE 4.31 Conversion of retinal to retinoic acid mediated by aldehyde dehydrogenase and the structure of disulfiram, an inhibitor of aldehyde dehydrogenase. 

Toxicology. Cyanamide is an irritant of the eyes, mucous membranes, and skin it is an inhibitor of aldehyde dehydrogenase and can cause an antabuse effect with ethanol ingestion. 

FALDH Fatty aldehyde dehydrogenase and fatty alcohol NAD-oxidoreducease phosphate oxidoreductase... 

Oxidation of acetaldehyde is inhibited by disulfiram, a drug that has been used to deter drinking by alcohol-dependent patients undergoing treatment. When ethanol is consumed in the presence of disulfiram, acetaldehyde accumulates and causes an unpleasant reaction of facial flushing, nausea, vomiting, dizziness, and headache. Several other drugs (eg, metronidazole, cefotetan, trimethoprim) inhibit aldehyde dehydrogenase and can cause a disulfiram-like reaction if combined with ethanol. 

Disulfiram appeared to act synergistically with tranquilizers, causing spontaneous miscarriages and/or malformations in the fetuses of five women. It also exerts powerful synergistic action with alcohol by inhibition of the enzyme of aldehyde dehydrogenase and acts similarly with EDB to magnify the toxicity and oncogenicity of the latter compound. 

In mammals, the liver enzymes aldehyde dehydrogenase and aldehyde oxidase appear to be mainly responsible for this reaction. 

Tasayco M. L. and Prestwich G. D. (1990b) A specific affinity reagent to distinguish aldehyde dehydrogenases and oxidases. Enzymes catalyzing aldehyde oxidation in an adult moth. J. Biol. Chem. 265, 3094-3101. 

Bosron WF, Li TK. Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism. Hepatology 1986 6 502-510. 

Hexogen (RDX) was first prepared in 1899 by Henning for medicinal use. (N.B. NG and PETN are also used in medicine to treat angina pectoris. The principal action of these nitrate esters is vasodilation (i.e. widening of the blood vessels). This effect arises because in the body the nitrate esters are converted to nitric oxide (NO) by mitochondrial aldehyde dehydrogenase, and nitric oxide is a natural vasodilator.) In 1920 Herz prepared RDX for the first time by the direct nitration of hexamethylene tetramine. Shortly afterwards Hale (Picatinny Arsenal, NJ) developed a process that formed RDX in 68 % yield. The two processes most widely used in WW II were... 

Mandel S, Grunblatt E, Riederer P, Amariglio N, Jacob-Hirsch J, Rechavi G, Youdim MB (2005) Gene expression profiling of sporadic Parkinson s disease substantia nigra pars compacta reveals impairment of ubiquitin-proteasome subunits, SKPIA, aldehyde dehydrogenase, and chaperone HSC-70. Ann N Y Acad Sci 1053 356-375. 

Boston, WJ ., Li, T.K. Genetic determinations of alcohol and aldehyd dehydrogenases and alcohol metabolism. Semin. Liver Dis. 1981 1 179-188... 

Alcohol is metabolized by the catalytic action of alcohol dehydrogenase, aldehyde dehydrogenase, and the ethanol-oxidizing system of the endoplasmic reticu-... 

Other mono-oxygenases are not cytochrome P450 dependent, such as flavoproteins located in the endoplasmic reticulum that are involved in the oxidation of tertiary amines to N-oxides and of various sulfur compounds. Yet other oxidative enzymes, including alcohol and aldehyde dehydrogenases and monoamine oxidases, are located in the mitochondria or cytosol. 

Metabolism involves the aldehyde dehydrogenase and the c)loehromc system. 

Figure 3 Oxidation of acetaldehyde and reduction of acetic acid by aldehyde dehydrogenase and the appropriate form of NAD+.

P Hu, L Jin, T Baillie. Studies on the metabolic activation of disulfiram in rat evidence for electrophilic S-oxygenated metabolites as inhibitors of aldehyde dehydrogenase and precursors of urinary N-acetylcysteine conjugates. J Pharmacol Exp Ther 281(2) 611—617, 1997. 

Disposition - It is possible that one mechanism for the disposition of the endogenously produced amine is by diffusion, which could be followed by re-uptake by nerve endings (or by other material in tissues) as has been shown with norepinephrine. But as yet there is no evidence for such a cycle for HT, although, as noted above, brain and its particulate fractions have the capacity for uptake. A main catabolic pathway for HT is oxidative deamination by monoamine oxidase to form 5-hy-droxyindoleacetaldehyde, most of which is converted to 5-hydroxyindole-acetic acid (HIAA) by aldehyde dehydrogenase and NAD S, 56 relatively small portion is reduced to 5-hydroxytryptophol by alcohol dehydrogenase and NADH " Monoamine oxidase, which, like... 

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