Aldehyde Dehydrogenases ALDH

ALDHs catalyze the oxidation of aldehydes to carboxylic acids, which is usually not reversible  

The reaction can be compared with that of the aldehyde oxidase vide supra) 

The ALDHs are concentrated in the liver, mainly in the mitochondria (Petersen and Lindahl, 1997). The human genome contains 19 putatively 

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The effect is mainly due to the inhibition of NAD+-dependent aldehyde dehydrogenase (ALDH) which causes an accumulation of acetaldehyde in the body after ethanol ingestion [17]. The compound responsible for the physiological activity of C. atramentarius is coprine 16, a AT -(l-hydroxycyclopropyl)-L-glutamic acid amide which has been isolated and synthesized, [16a,b]. Thus, when fed... 

Thus the cyclopropanone hydrate 21 is an inhibitor of yeast aldehyde dehydrogenase (ALDH) through the nucleophilic substitution of a hydroxyl group by an enzymic thiol 47 leading to the cyclopropanone hemithioacetal 24 a, Eq. (16) [211. 

Newer strategies for stem cell identification have been developed based on the knowledge of cell functions. A primitive and multipotential subpopulation of bone marrow mononuclear cells has been identified on the basis of the intracellular presence of aldehyde dehydrogenase (ALDH). Those cells can be marked on the basis of the presence of ALDH and are called aldehyde dehydrogenase-bright cells (ALDH cells), allowing for their separation from a bone marrow aspiration mononuclear subpopulation under fluorescence-activated cell sorter (FACS) analysis. 

Much of the acetaldehyde formed from alcohol is oxidized in the liver in a reaction catalyzed by mitochondrial NAD-dependent aldehyde dehydrogenase (ALDH). The product of this reaction is acetate (Figure 23-1), which can be further metabolized to C02 and water, or used to form acetyl-CoA. 

Acetaldehyde is oxidized to acetic acid by NAD+-dependent aldehyde dehydrogenases (ALDH) in liver and nasal mucosal preparations. Its administration to rats causes an increase in urinary excretion of sulfur metabolites and it is known to react with cysteine to produce a thiazolidine 4-carboxylic acid derivative that can be A -nitro-sated in vivo upon co-administration of nitrite (lARC, 1985). Many studies have been published subsequently, but these have been mainly in the context of ethanol metabolism. 

Unlike many DNA alkylators, cyclophosphamide shows modest selectivity for cancer cells. Healthy tissues in a patient have high levels of aldehyde dehydrogenase (ALDH). ALDH reduces the potency of cyclophosphamide by oxidizing 6.32 to 6.34, an inactive compound. Cancerous cells tend to be deficient in ALDH and more prone to damage by cyclophosphamide. 

A subsequent oxidation, catalyzed by aldehyde dehydrogenase (ALDH), converts acetaldehyde to acetic acid, a normal metabolite. 

Alcohol dehydrogenase (ADH) is involved in the metabolism of ethanol to acetaldehyde, which in turn is converted to acetate by aldehyde dehydrogenase (ALDH). Because the hepatic expressions of these enzymes are influenced by both ethanol consumption and liver cirrhosis, which may be the consequence of ethanol consumption, it is sometimes difficult to know which of these factors is resulting in modulation of the enzyme. There is generally a reduction in ADH in alcoholic cirrhosis [77, 78], whereas in non-alcoholic cirrhotic patients some studies have detected a reduction in ADH [77] but others have detected no change [78]. Total ALDH is reduced in primary biliary cirrhosis, alcoholic and non-alcoholic cirrhosis compared to controls [77, 78]. 

In a subsequent, and likewise NAD-dependent reaction, the highly toxic acetaldehyde is converted to acetic acid in the mitochondria by way of aldehyde dehydrogenase (ALDH). The resulting NADH is then reoxidized. (60, 78) (s. fig. 3.16)... 

Fig. 3.16 Diagram showing alcohol degradation in the liver cell by means of alcohol dehydrogenase (ADH), catalase and the microsomal-ethanol oxidizing system (MEOS) as well as by aldehyde dehydrogenase (ALDH)...

Toxic acetaldehyde resulting from alcohol oxidation is almost completely oxidized to acetate in the liver cell by aldehyde dehydrogenase (ALDH). For this purpose, various NAD-dependent ALDH isoenzymes are available. Isoenzyme II is bound to the mitochondrial matrix, while isoenzymes I, III and IV are found in the cytosol as well as in the microsomes and, to a lesser degree, in the mitochondria. They also exhibit biochemical differences. Acetaldehyde can be oxidized either by ALDH or by xan-... 

Alnouti Y, Klaassen CD (2008) Tissue distribution, ontogeny, and regulation of aldehyde dehydrogenase (Aldh) enzymes mRNA by prototypical microsomal enzyme inducers in... 

Aldehyde dehydrogenases (ALDH), a large superfamily of enzymes produced by 19 human genes in 11 families and 13 subfamilies. 

MALDI-TOF MS, but only a few representative proteins were listed in the figure eaption of their 2-DE gel. However, their focus was to examine the differences in the electrophoretic pattern of aldehyde dehydrogenase (ALDH) between normal and tumorous tissues on 2-DE gels. They showed that alterations of the aldehyde dehydrogenase isozyme variants, ALDH-3 and ALDH-2, are closely correlated to HCC. This suggests that a proteomic approach could be used to identify potential biomarkers of HCC, and to elucidate molecular changes in hepatocarcinogenesis (Park et al., 2002). 

Alternative paths have also been provided where the bioactivation product is very prone to oxidation, forming sulfenic and sulfinic acids, S-methylation, and ultimate metabolization to A-methyl metam oxon as a potential aldehyde dehydrogenase (ALDH) inhibitor (Scheme 23) <1995CRT1063>. 

Vasiliou V, Nebert DW. Analysis and update of the human aldehyde dehydrogenase (ALDH) gene family. Hum Genomic 2005 2 138-143. 

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