Disease relevance of Adh4

• Like the rat, human, and Escherichia coli class III ADHs, the rabbit enzyme is a glutathione-dependent formaldehyde dehydrogenase, and catalyzes the oxidation of S-hydroxymethylglutathione and the hemithiolacetal of 8-thiooctanoic acid [1].
• We expressed the NH2-terminal domain of the multidomain, multifunctional enzyme, 10-formyltetrahydrofolate dehydrogenase (FDH), using a baculovirus expression system in insect cells [2].
• This allowed us to examine the relationship between distribution of FDH and formaldehyde-induced toxicity [3].

High impact information on Adh4

• Also, the administration of a single dose of dihydrotestosterone inhibited liver alcohol dehydrogenase 4 hr after the injection, but this effect was not persistent at later intervals following injection [4].
• NAD+ at physiological concentrations stimulated the aldehyde dehydrogenase reaction performed by FDH or its COOH-terminal domain using NADP+ [5].
• The purified COOH-terminal domain displayed aldehyde dehydrogenase activity similar to that of native FDH but had neither dehydrogenase nor hydrolase activity toward folate substrates [5].
• Titration of tryptophan fluorescence showed that native FDH bound both the substrate of the reaction, 10-formyl-5, 8-dideazafolate, and the product of the reaction, 5,8-dideazafolate, with the same affinities as its NH2-terminal domain did and that both proteins bound the substrate with a 50-fold higher affinity than the product [2].
• The liver cytosolic enzyme, 10-formyltetrahydrofolate dehydrogenase (FDH) (EC 1.5.1.6) catalyzes two reactions: the NADP+-dependent oxidation of 10-formyltetrahydrofolate to tetrahydrofolate and CO2 and the NADP+-independent hydrolysis of 10-formyltetrahydrofolate to tetrahydrofolate and formate [5].

Chemical compound and disease context of Adh4

• While high aldehyde dehydrogenase activities were found in tissues with low toxicities due to acetaldehyde exposure and vice versa, FDH activity was observed in tissues whether or not they exhibited a toxic response to inhaled HCHO [3].

Biological context of Adh4

• The immunocytochemical results showed the presence of FALDH binding sites in both the cytoplasm and the nucleus of the different cell types studied [6].
• We propose that one of the functions of FALDH is to protect cell structures, including DNA, from the toxic effects of endogenous formaldehyde, which is an intermediate in many metabolic process [6].
• We determined the amino acid sequences for 5 tryptic peptides (containing altogether 57 amino acids) from electrophoretically homogeneous rat liver formaldehyde dehydrogenase and found that they all were exactly homologous to the sequence of rat liver class III alcohol dehydrogenase (ADH-2) [7].
• Abundant levels of class-III alcohol-dehydrogenase (glutathione-dependent formaldehyde dehydrogenase) mRNA were present in all tissues analyzed, reflecting the general need for scavenging of formaldehyde in physiological cytoprotection [8].
• Sex differences of FDH activity in kidneys were not observed in F-344 rats [9].

Anatomical context of Adh4

• In the present work we used biochemical and immunocytochemical methods to assess the distribution of FALDH in rat hepatocytes and astroglial cells [6].
• Marked cyclical changes of alcohol dehydrogenase 4 activity in the stratum germinativum of the vaginal epithelium strongly support the assumption that this isoenzyme is responsible for retinoic acid synthesis, and that it is essential for the changes accompanying keratinization and mucification [10].
• We propose that ADHII represents the previously observed additional retinoid oxidation activity of rat liver cytosol which occurred in the presence of either ethanol or 4-methylpyrazole [11].
• The specific activity of FDH in the olfactory mucosa was twice that in the respiratory mucosa, whereas the specific activity of the higher Km isozyme of AldDH was five to eight times greater in respiratory than in olfactory tissue [12].
• Brain white matter stained strongly for FDH, while in gray matter only the neuropil exhibited weak activity [3].

Associations of Adh4 with chemical compounds

• S-Nitrosoglutathione is a substrate for rat alcohol dehydrogenase class III isoenzyme [13].
• ADH-2 (class III isoenzyme) is present in all organs but has a poor activity with ethanol [14].
• We conclude that the activity measured with 6-methoxy-2-naphthaldehyde (MONAL-62) may be due to the activity of rat ADH-1 isoenzyme, and the activity detected with 4-methoxy-1-naphthaldehyde (MONAL-41) to the activity of rat ADH-2 isoenzyme [15].
• Analysis of rat cytosolic 9-cis-retinol dehydrogenase activity and enzymatic characterization of rat ADHII [11].
• Neither ethanol nor 4-methylpyrazole inhibits the 9-cis-retinol dehydrogenase activity of rat ADHII [11].

Other interactions of Adh4

• Rat ADH-1, ADH-2 and ADH-3 exhibit many analogies with human ADH classes II, III and I respectively [16].

Analytical, diagnostic and therapeutic context of Adh4

• Both FDH and its COOH-terminal domain also bound NAD+ (Kd 11 and 16 microM, respectively) as measured by fluorescence titration [5].

References