Isoform-specific alanine aminotransferase measurement can distinguish hepatic from extrahepatic injury in humans

Rafter,Ingalill; Gråberg,Truls; Kotronen,Anna; Strömmer,Lovisa; Mattson,C.  Mikael; Kim,Ray  W.; Ehrenborg,Ewa; Andersson,Håkan B.; Yki-Järvinen,Hannele; Schuppe-Koistinen,Ina; Ekblom,Björn; Cotgreave,Ian; Glinghammar,Björn

doi:10.3892/ijmm.2012.1106

Isoform-specific alanine aminotransferase measurement can distinguish hepatic from extrahepatic injury in humans

Authors:
- Ingalill Rafter
- Truls Gråberg
- Anna Kotronen
- Lovisa Strömmer
- C. Mikael Mattson
- Ray W. Kim
- Ewa Ehrenborg
- Håkan B. Andersson
- Hannele Yki-Järvinen
- Ina Schuppe-Koistinen
- Björn Ekblom
- Ian Cotgreave
- Björn Glinghammar
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Affiliations: Safety Assessment, AstraZeneca, Södertälje, Sweden, Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Surgery, Karolinska Institute at Karolinska University Hospital, Huddinge, Stockholm, Sweden, Department of Medicine, University of Helsinki, Helsinki, Finland, Åstrand Laboratory of Work Physiology, Swedish School of Sport and Health Sciences, Karolinska Institute, Stockholm, Sweden, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA, Department of Medicine, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden
Published online on: August 23, 2012 https://doi.org/10.3892/ijmm.2012.1106
Pages: 1241-1249

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Abstract

Serum alanine aminotransferase (ALT) is used as a clinical marker to detect hepatic damage and hepatoxicity. Two isoforms of ALT have been identified, ALT1 and ALT2, which have identical enzymatic capacities and are detected simultaneously in human serum/plasma using classical clinical chemical assays. Differences exist in the expression patterns of the ALT1 and ALT2 proteins in different organs which suggest that changes in the proportion of ALT1 and ALT2 in plasma may arise and reflect damage to different human organs. However, this has not been previously studied due to the lack of a selective methodology that can quantify both ALT1 and ALT2 isoforms in the total ALT activity normally measured in clinical samples. To the best of our knowledge, our current study reveals for the first time, that under 3 different conditions of liver damage (non-alcoholic fatty liver disease, hepatitis C and during liver surgery) the leakage of ALT1 activity into plasma greatly exceeds that of ALT2, and that the measurement of ALT1 during liver damage is equal to the measurement of total ALT activity. By contrast, during skeletal muscle injury, induced in volunteers by physical exertion, the leakage of ALT2 exceeds that of ALT1 and the proportion of circulating ALT isoforms changes accordingly. The ALT isoform changes occurring in plasma reflect previously demonstrated relative contents of ALT1 and ALT2 activities in human liver and skeletal muscle. These data suggest that assessing the percentage contribution of ALT1 and ALT2 activities to total ALT activity in plasma may distinguish hepatic from extrahepatic injury using the same standard analytical platform.

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