Glutamate Dehydrogenase as a Marker of Alcohol Dependence

Kravos, Matej; Malešič, Ivan

doi:10.1093/alcalc/agp070

Cited by 10 publications

(12 citation statements)

References 15 publications

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“…GLDH converts glutamate to α-ketoglutarate releasing ammonia and vice versa, whereas GS condenses glutamate and ammonia to glutamine. Although GLDH has been suggested to be a potential alcohol dependence biomarker, 44 we found that GS activity could be an underlying mechanism for positive acamprosate treatment outcome as glutamine was negatively correlated with both glutamate and ammonia in the responder group. It is important to note that acamprosate is most effective in maintaining abstinence when patients were detoxified before initiating acamprosate treatment.…”

Section: Discussionmentioning

confidence: 61%

“…It is also important to consider that ammonia can cross the blood–brain barrier and has been shown to result in increased glutamate levels in the brain. 43 As glutamate dehydrogenase (GLDH) and GS have an important role in signaling regulation in alcohol dependence, 44 we also analyzed their metabolic products. GLDH converts glutamate to α-ketoglutarate releasing ammonia and vice versa, whereas GS condenses glutamate and ammonia to glutamine.…”

Section: Discussionmentioning

confidence: 99%

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Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects

et al. 2015

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Acamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneous disorder. Thus, biomarkers are required to prescribe this medication to patients who will have the highest likelihood of responding positively. To identify pharmacometabolomic biomarkers of acamprosate response, we utilized serum samples from 120 alcohol-dependent subjects, including 71 responders (maintained continuous abstinence) and 49 non-responders (any alcohol use) during 12 weeks of acamprosate treatment. Notably, baseline serum glutamate levels were significantly higher in responders compared with non-responders. Importantly, serum glutamate levels of responders are normalized after acamprosate treatment, whereas there was no significant glutamate change in non-responders. Subsequent functional studies in animal models revealed that, in the absence of alcohol, acamprosate activates glutamine synthetase, which synthesizes glutamine from glutamate and ammonia. These results suggest that acamprosate reduces serum glutamate levels for those who have elevated baseline serum glutamate levels among responders. Taken together, our findings demonstrate that elevated baseline serum glutamate levels are a potential biomarker associated with positive acamprosate response, which is an important step towards development of a personalized approach to treatment for AUD.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects

et al. 2015

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“…Glutamate dehydrogenase (GLDH) has been used as a marker of liver function as well as a marker for recent alcohol consumption in alcoholics (Kravos and Malesic, 2010). This reaction proceeds towards the direction of oxidative deamination of glutamate, which releases ammonia, normally with an activity of 6.4 U/L for women and 11.0 U/L for men.…”

Section: The Digestive Systemmentioning

confidence: 99%

The Measurement of Ammonia in Human Breath and its Potential in Clinical Diagnostics

Brannelly

Shield

Killard

2016

Critical Reviews in Analytical Chemistry

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“…Using proteomic technologies, elevated levels of IgA, α1-antichymotrypsin, haptoglobins, apoprotein A-I, or decreased apoprotein A-II and fibrinogen αE chain, were identified [48]. The increase in glutamate dehydrogenase and urinary alanine aminopeptidase, the decrease in erythrocyte aldehyde dehydrogenase, or increase in serum hyaluronate, were also suggested as a glycoconjugate-related markers of alcohol-dependence and alcohol-induced tissue damage [15,40,49]. However, all the aforementioned markers need further confirmatory research.…”

Section: Other Markersmentioning

confidence: 99%

Glycoconjugates in the detection of alcohol abuse

Waszkiewicz

Szajda

Kępka

et al. 2011

Biochemical Society Transactions

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Up to 30% of all hospital admissions and health-care costs may be attributable to alcohol abuse. Ethanol, its oxidative metabolites, acetaldehyde and ROS (reactive oxygen species), non-oxidative metabolites of alcohol [e.g. FAEEs (fatty acid ethyl esters)] and the ethanol-water competition mechanism are all involved in the deregulation of glycoconjugate (glycoprotein, glycolipid and proteoglycan) metabolic processes including biosynthesis, modification, transport, secretion, elimination and catabolism. An increasing number of new alcohol biomarkers that are the result of alcohol-induced glycoconjugate metabolic errors have appeared in the literature. Glycoconjugate-related alcohol markers are involved in, or are a product of, altered glycoconjugate metabolism, e.g. CDT (carbohydrate-deficient transferrin), SA (sialic acid), plasma SIJ (SA index of apolipoprotein J), CETP (cholesteryl ester transfer protein), β-HEX (β-hexosaminidase), dolichol, EtG (ethyl glucuronide) etc. Laboratory tests based on changes in glycoconjugate metabolism are useful in settings where the co-operativeness of the patient is impaired (e.g. driving while intoxicated) or when a history of alcohol use is not available (e.g. after trauma). In clinical practice, glycoconjugate markers of alcohol use/abuse let us distinguish alcoholic from non-alcoholic tissue damage, having important implications for the treatment and management of diseases.

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Glutamate Dehydrogenase as a Marker of Alcohol Dependence

Abstract: GLDH is an equally accurate marker of alcoholism in comparison to others, if its significantly faster decrease is taken into consideration. We strongly believe that watching changes in the activity of laboratory markers of alcoholism is an effective yet overlooked aid.

Cited by 10 publications

References 15 publications

Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects

Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects

The Measurement of Ammonia in Human Breath and its Potential in Clinical Diagnostics

Glycoconjugates in the detection of alcohol abuse

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