Cytosolic Aldehyde Dehydrogenase and Alcoholism

Agarwal, D. P.; Harada, Shoji; Goedde, H. W.; Schrappe, O

doi:10.1016/s0140-6736(83)91600-8

Cited by 18 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is also unknown whether S -nitrosylated hepatic ALDH1A1 and ALDH2 observed in alcohol-exposed rodents represent a cellular protective mechanism (e.g., prevention from irreversible hyper-oxidation to sulfinic/sulfonic acids), as proposed for the S -nitrosylated proteins in cardiac tissues [64,65] or simply reflect the inactivated proteins per se . Since the liver possesses a high capacity of regenerating or refurbishing the antioxidants through activation of a protective transcription factor Nrf-2 and other genes, the latter case looks more physiological and consistent with the suppressed ALDH activities observed in human alcoholic individuals [56,57]. Thus, based on the conflicting views, the physiological role of S -nitrosylation of hepatic ALDH2 and other ALDH isozymes in alcoholic and nonalcoholic fatty liver or fibrotic/cirrhotic diseases need re-evaluation in the future.…”

Section: Post-translational Modifications Of Aldh2 and Aldh Isozymesmentioning

confidence: 60%

“…The structural alignment and comparison revealed that the active site Cys residue is 100% conserved among the 17 ALDH isozymes (see Table 1). Because of the suppressed ALDH2 and ALDH1 activities in alcoholic individuals [56,57] or rodents exposed to alcohol [30–35], which increases oxidative/nitrosative stress [58–61], it is expected that the critical Cys residues including the highly-conserved active site Cys could be oxidatively-modified and thus inactivated. In fact, our proteomics analyses showed that cytosolic ALDH1A1, mitochondrial ALDH2, and other isozymes such as ALDH5A1 and ALDH6A1 were oxidatively-modified in rats exposed to alcohol [32–35] or 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) [36] and after hepatic ischemia-reperfusion (I/R) injury [37].…”

Section: Post-translational Modifications Of Aldh2 and Aldh Isozymesmentioning

confidence: 99%

See 1 more Smart Citation

Post-translational modifications of mitochondrial aldehyde dehydrogenase and biomedical implications

Song¹,

Abdelmegeed²,

Yoo³

et al. 2011

Journal of Proteomics

View full text Add to dashboard Cite

Aldehyde dehydrogenases (ALDHs) represent large family members of NAD(P)+-dependent dehydrogenases responsible for the irreversible metabolism of many endogenous and exogenous aldehydes to the corresponding acids. Among 19 ALDH isozymes, mitochondrial ALDH2 is a low Km enzyme responsible for the metabolism of acetaldehyde and lipid peroxides such as malondialdehyde and 4-hydroxynonenal, both of which are highly reactive and toxic. Consequently, inhibition of ALDH2 would lead to elevated levels of acetaldehyde and other reactive lipid peroxides following ethanol intake and/or exposure to toxic chemicals. In addition, many East Asian people with a dominant negative mutation in ALDH2 gene possess a decreased ALDH2 activity with increased risks for various types of cancer, myocardial infarct, alcoholic liver disease, and other pathological conditions. The aim of this review is to briefly describe the multiple post-translational modifications of mitochondrial ALDH2, as an example, after exposure to toxic chemicals or under different disease states and their pathophysiological roles in promoting alcohol/drug-mediated tissue damage. We also briefly mention exciting preclinical translational research opportunities to identify small molecule activators of ALDH2 and its isozymes as potentially therapeutic/preventive agents against various disease states where the expression or activity of ALDH enzymes is altered or inactivated.

show abstract

Section: Post-translational Modifications Of Aldh2 and Aldh Isozymesmentioning

confidence: 60%

Section: Post-translational Modifications Of Aldh2 and Aldh Isozymesmentioning

confidence: 99%

Post-translational modifications of mitochondrial aldehyde dehydrogenase and biomedical implications

Song¹,

Abdelmegeed²,

Yoo³

et al. 2011

Journal of Proteomics

View full text Add to dashboard Cite

show abstract

“…Liver cytosolic aldehyde dehydrogenase is similar to the red cell enzyme. The latter was reduced in alcoholics but returned to normal after cessation of drinking (84). In the liver of alcoholics, there is also a decrease of liver aldehyde dehydrogenase activity which may (85) or may not (86) be reversible on cessation of drinking.…”

Section: Toxic Effects Of Acetaldehyde Acetaldehyde Blood Levelsmentioning

confidence: 97%