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ETHYL GLUCARANIDE

BIOCHEMISTRY

mprasadnaidu
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ETHYL GLUCARANIDE

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  1. ETHYLGLUCURONIDE M.Prasad Naidu MSc Medical Biochemistry, Ph.D,. .

  2. A range of biomarkers for detecting alcohol misuse have been described • Ethanol – in breath, blood or urine. • 5-hydroxytryptophol / 5-hydroxyindoleacetic acid ratio ( 5-HTOL / 5-HIAA ). • Ethyl glucuronide ( EtG ). • Ethyl sulphate ( EtS ). • Gamma-glutamyltranspeptidase ( GGT ). • Carbohydrate-deficient transferrin ( CDT ). • Fatty acid ethyl esters (FAEEs ). • Erythrocyte mean corpuscular volume ( MCV).

  3. Ethanolmeasurements have high specificity for excessive alcohol intake, but the time window for positivity is short ( breath 4-6 h, blood 10-12 h, urine 18-24 h ). • MCV & GGTrequire significant alcohol intake over a prolonged period of time ( > 1000 g over atleast two weeks ) to become abnormal & have poor specificity as both can be rised in chronic disease, nutritional deficiencies & obesity.

  4. FAEEsare esterification products of ethanol & fatty acids that have been implicated as mediators of alcohol induced organ damage, & measured in blood & tissues as markers of alcohol intake. • The ratio of 5-HTOL / 5-HIAA in urine was shown to be a more sensitive & specific marker of alcohol ingestion than urine ethanol or methanol, remaining positive for 6 -15 h after the BAC had returned to baseline values.

  5. CDThas good specificity for alcohol misuse, but is a marker of alcohol misuse over a 7-14 d period & does not become positive after a single session of heavy drinking.

  6. Exessive drinking in one session, ‘binge’ drinking, appears to be on the increase in some societies. • There is, therefore, a need for a biomarker that will be positive in the gap in the time window, between one day & one week, left by the current biomarkers of alcohol consumption.

  7. Ethyl glucuronide ( EtG )is a direct metabolite of ethanol formed by the enzymatic conjugation of ethanol with glucuronic acid in liver. • This phase II reaction is catalysed by mitochondrial membrane-bound UDP-glucuronosyltransferase. • Ethanol is also conjugated to sulphate by sulfotransferase to formethyl sulphate ( EtS )

  8. EtG & EtS are most commonly measured in urine as markers for alcoholintake. • EtG has also been detected in postmortem hair samples together with tissue samples ( gluteal & abdominal fat, liver & brain ) from intoxicatedsubjects.

  9. EtG has been shown to be a stablemarker. • Studies have shown that urine samples stored at 4ºC for five weeks were found to have no change in EtG concentration. • EtG : 100-200µg/L , • EtS : 100-110µg/L. • In routine clinical use, cut-offs as high as 500µg/L have been used to reduce the risk of false-positive results.

  10. The most commonly used method is Liquid chromatography - mass spectrometry ( LC-MS ) since it is highly sensitive, specific & is able to determine both EtG & EtS simultaneously. • This technology has been used to determine EtG in urine, whole blood, serum, muconium, saliva & hair.

  11. Recently, a commercially available enzymeimmunoassay (EIA ) methodbased on a new monoclonal antibody came into the market for the analysis of EtG in urine. • The method evaluation showed that the EIA is sensitive & specific. • The EIAmethod is considered a screening test & EtG positive samples should always be confirmedbyLC-MS with EtS to rule out false positives due to contamination.

  12. The largest study incorporating EtG measurements was the World Health Organization / International Society for Biomedical Research on Alcoholism ( WHO / ISBRA ) Study of State & Trait Markers of Alcohol Use & Dependence that recruted 304 subjects from Brazil & Australia of whom 158 were diagnosed as lifetime alcohol abusers. • The study also measured the 5-HTOL / 5-HIAA ratio in urine, blood ethanol & serum CDT & GGT. • The authers concluded that EtG was a good candidate for a sensitive, specific & reliable marker of recent alcohol intake.

  13. conclusions • EtGhaspotentialasamarkerof high sensitivity & specificity for the detection of alcoholmisusein a varity of settings, both in clinical & forensic medicine. • As non invasive marker, EtG in urine or hair could have a role in screening, diagnosis & monitoring treatment.

  14. Urine EtGremainspositive for periods upto90h following heavy alcohol consumption; therefore, providing a marker with an intermediate timeframe between ethanol measurements & GGT / CDT. • This may prove perticularly useful in workplace monitoring schemes, prior to & following livertransplantation, alcoholdetoxificationprogrammes & in the identification of neonates at risk of Fetal alcohol syndrome ( FAS ).

  15. THAN “Q”

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