Acetaldehyde-enkephalins: structure proof and some conformational deductions from one- and two-dimensional proton nuclear magnetic resonance spectra

Gidley, Michael J.; Hall, Laurance D.; Sanders, Jeremy K. M.; Summers, Michael C.

doi:10.1021/bi00516a033

Cited by 19 publications

(3 citation statements)

References 18 publications

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“…The cy clic adduct formed is a 2-methyl-imidazolidin-4-one. whose structure has been confirmed using proton NMR spectroscopy [21], 13C-NMR spectroscopy [22], and mass spectrom etry [23]. The imidazolidinone ring can open to regenerate the unstable Schiff base.…”

Section: Chemistry and Functional Consequences Of Ach Reactions With mentioning

confidence: 99%

Acetaldehyde/ Protein Interactions: Are They Involved in the Pathogenesis of Alcoholic Liver Disease?

Worrall

Jersey²,

Nicholls³

et al. 1993

Dig Dis

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Alcohol abuse is a major cause of liver disease. While ethanol itself has been shown to be hepatotoxic, its primary metabolite acetaldehyde has also been implicated in the pathogenesis of alcoholic liver disease. The majority of ethanol metabolism occurs in the liver and high concentrations of acetaldehyde accumulate during chronic ethanol abuse. Acetaldehyde has been shown to react with many proteins in vitro, forming stable covalent adducts. These modifications can act as neoantigens and may also alter biological function. Acetaldehyde-modified proteins have been detected in the livers of ethanolfed rats and human alcoholics. Circulating antibodies reactive with modified proteins have also been detected. A direct linkage between acetaldehyde-modified proteins, antibodies and liver damage has yet to be established, but current research should clarify the picture in the next few years.

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Section: Chemistry and Functional Consequences Of Ach Reactions With mentioning

confidence: 99%

Acetaldehyde/ Protein Interactions: Are They Involved in the Pathogenesis of Alcoholic Liver Disease?

Worrall

Jersey²,

Nicholls³

et al. 1993

Dig Dis

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show abstract

“…In the case of hemoglobin, different Ach adducts have been hypothesized. If the adduct involves the N-terminal end of hemoglobin, the cyclization of the Schiff base results in a stable imidazolidinone [14,15]. Other unstable Schiff bases can be stabilized by reduction under in vivo conditions by ascorbate [16] and NADH [17].…”

Section: Introductionmentioning

confidence: 99%

A new CE‐ESI‐MS method for the detection of stable hemoglobin acetaldehyde adducts, potential biomarkers of alcohol abuse

Benedetto

Fanigliulo

2009

Electrophoresis

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A new CE-ESI-MS method was developed to provide a simple way to study changes to hemoglobin (HbA) induced by acetaldehyde (Ach) in vitro. Instrumental parameters were univariately optimized in order to maximize the sensitivity of the CE-ESI-MS method. The electrophoretic separations were carried out in poly-E323-coated capillaries using 60 mM formic acid raised to pH 3.0 with ammonia and containing 5% 2-propanol while the sheath liquid, 2-propanol/water (30:70) with 0.1% formic acid, was delivered at 1.0 microL/min through a coaxial sheath flow electrospray interface. The HbA was incubated with Ach for intervals up to 24 h at concentration varying in the window 0.2-20 mM. Four stable Ach-hemoglobin adducts in the hemoglobin tryptic digest were observed at the submillimolar Ach concentration and characterized by MS/MS experiments: although the alpha and beta N-amino terminal modifications were expected, the two internal ones arising, respectively, from the condensation of Ach molecules on the histidine residue in position 4 in alpha4 (i.e. the fourth peptide after tryptic digestion of alpha chain starting from amino terminal) and on the asparagine residue in position 2 in beta3, were identified for the first time. During the in vitro experiments higher concentrations of Ach were also used; however, it was not possible to identify any other stable modification of hemoglobin. Interestingly, those stable modifications are the only ones in vivo identified in the hemoglobin of moderate alcohol drinkers.

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“…In the case of hemoglobin, several types of adducts have been identified that are due to modification by acetaldehyde. Irreversible products have been identified at the N-terminal end of hemoglobin as a result of stabilization of the Schiff base by cyclization to produce the imidazolidinone ( , ). Scheme shows the mechanism of the reaction with N-terminal peptides.…”

Section: Introductionmentioning

confidence: 99%

Stable Acetaldehyde−Protein Adducts as Biomarkers of Alcohol Exposure

Birt

Shuker

Farmer

1998

Chem. Res. Toxicol.

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The consumption of alcoholic beverages has been associated with increased risks of a number of chronic disorders including cancers. It is still not clear whether ethyl alcohol or other components such as metabolites are directly involved in the carcinogenic process or whether the effects are due to the modulation of metabolism of other carcinogens. At present, there is no good biomarker of alcohol intake, particularly at low or moderate levels of consumption. A number of studies have shown the ability of the major metabolite acetaldehyde to react with proteins in vitro to give stable and unstable adducts. The interaction of acetaldehyde with model peptides, which correspond to N-terminal globin sequences, was studied. The major stable adduct was identified by mass spectrometry and NMR as a diastereoisomeric mixture of imidazolidinones. This is believed to be formed by reaction and cyclization of the initial Schiff base adduct with the N-terminal valine. Incubation of human globin with acetaldehyde (0-2 mM) yielded products which were identified as the N-terminal adducts by electrospray ionization mass spectrometry (ESI-MS) of proteolytic digests. The specificity and sensitivity of the analysis was improved by the use of on-line HPLC-ESI-MS. Tryptic digests of the modified globin which contained both the N-terminal acetaldehyde adducts of alpha-globin (heptapeptide) and beta-globin (octapeptide) were resolved. These results suggest that analysis of stable imidazolidinone adducts is a promising approach to estimation of alcohol exposure.

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Acetaldehyde-enkephalins: structure proof and some conformational deductions from one- and two-dimensional proton nuclear magnetic resonance spectra

Cited by 19 publications

References 18 publications

Acetaldehyde/ Protein Interactions: Are They Involved in the Pathogenesis of Alcoholic Liver Disease?

Acetaldehyde/ Protein Interactions: Are They Involved in the Pathogenesis of Alcoholic Liver Disease?

A new CE‐ESI‐MS method for the detection of stable hemoglobin acetaldehyde adducts, potential biomarkers of alcohol abuse

Stable Acetaldehyde−Protein Adducts as Biomarkers of Alcohol Exposure

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