Catalytic Enzyme Activity Concentration in Tissues of Man, Dog, Rabbit, Guinea Pig, Rat and Mouse. Approach to a Quantitative Diagnostic Enzymology, III. Communication

Lindena, J.; Sommerfeld, Ute; Höpfel, Cornelia; Trautschold, I.

doi:10.1515/cclm.1986.24.1.35

Cited by 21 publications

(26 citation statements)

References 24 publications

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“…The cloning of ALT2 and the demonstration of differential tissue expression at mRNA levels for GPT1 and 2 (5,15), led to the hypothesis that increased serum ALT levels are caused by a specific leakage of ALT2 from other organs than the liver (5). Indeed, ALT activity was found in other organs, mostly in the kidneys (50% of liver activity/g tissue), heart (20%), skeletal muscle (10-20%) and pancreas (16,17). The basal levels of ALT in blood are, in part, a result of a poorly understood process involving hepatocytes and possibly turnover in other tissues.…”

Section: Discussionmentioning

confidence: 99%

Detection of the mitochondrial and catalytically active alanine aminotransferase in human tissues and plasma

Glinghammar

Rafter²,

Lindström³

et al. 2009

Int J Mol Med

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Abstract. Serum alanine aminotransferase (ALT) is used as a clinical marker of hepatotoxicity. Three forms of human ALT have been identified, ALT1 and 2 and an alternative splice variant of ALT2 (herein called ALT2_2). The standard ALT activity assay does not discriminate between ALT from different organs, or the isoforms measured in the plasma. Here, we show that ALT1 and 2 possess similar enzymatic activity for alanine and pyruvate but with different K m and k cat values, while recombinant ALT2_2 protein does not possess any enzymatic activity. Isolation of organelles from cultured human skeletal muscle cells, showed localisation of ALT2 to the mitochondrial fraction and endoplasmatic reticulum (ER), but not to the cytosol. In human hepatocytes, on the other hand, ALT1 was only localised to the cytosol and ER, with no detection in mitochondria. ALT2 was not detected in cultured human hepatocytes, liver extract or tissue using Western blotting or immunohistochemistry. The islet of Langerhans and cardiomyocytes were other examples of cells with high expression of catalytic ALT2. A clinical method for selective measurement of ALT1 and 2 in human plasma is described, and both ALT1 and 2 were immunoprecipitated from human plasma and structurally detected using Western blotting techniques.

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Section: Discussionmentioning

confidence: 99%

Detection of the mitochondrial and catalytically active alanine aminotransferase in human tissues and plasma

Glinghammar

Rafter²,

Lindström³

et al. 2009

Int J Mol Med

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“…Total CK activities are also relatively high in myocardium, intestine and brain. In other organs very low activities, usually less than 2% of muscle activity, can be observed (Henry et al, 1970;Clampitt and Hart, 1978;Keller, 1979Keller, , 1981Mickelson et al, 1985;Lindena et al, 1986c;Mattheeuws et al, 1990). The distribution of CK isoenzymes in dogs differs significantly from that in humans, mainly for the MB isoenzyme (Table III).…”

Section: Distribution In the Organs Of The Dogmentioning

confidence: 99%

Creatine kinase in the dog: A review

et al. 1993

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In the dog, creatine kinase (CK) is mostly present in the skeletal muscles, myocardium, brain and intestine. The MM isoenzyme predominates in muscles and myocardium. In plasma, reference values depend on the technique used and CK-MB accounts for about 30-45% of total CK activity. Sex has no influence on plasma CK activity, which is higher in young dogs than in adults. Plasma CK is elevated after physical exercise. After its release from the cells, CK reaches the plasma mostly via the lymphatic route and then remains in the plasma compartment. It is rapidly cleared with a half-life of about 2 hours. Muscle diseases are the main source of plasma CK elevations: inherited myopathies, malignant hyperthermia, hypothyroidism, vitamin E-selenium deficiency, prolonged decubitus, intramuscular injections, surgery, etc. Plasma CK is also increased in experimental myocardial infarction, for which the dog is an interesting model, allowing quantification of the damage by measuring the total CK activity released.

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“…The ALT enzyme plays an important role in amino acid metabolism and gluconeogenesis by catalyzing reversible transamination between L-alanine and α-ketoglutarate to form pyruvate and glutamate. While the liver is the most ALT-enriched organ in the human body, ALT activity is also found in other organs, such as the heart, kidney and skeletal muscle (2). Two isoforms of ALT have been discovered, ALT1 and ALT2, which originate from 2 discrete genes (3,4).…”

Section: Introductionmentioning

confidence: 99%

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

Rafter

Gråberg

Kotronen

et al. 2012

International Journal of Molecular Medicine

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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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Catalytic Enzyme Activity Concentration in Tissues of Man, Dog, Rabbit, Guinea Pig, Rat and Mouse. Approach to a Quantitative Diagnostic Enzymology, III. Communication

Cited by 21 publications

References 24 publications

Detection of the mitochondrial and catalytically active alanine aminotransferase in human tissues and plasma

Detection of the mitochondrial and catalytically active alanine aminotransferase in human tissues and plasma

Creatine kinase in the dog: A review

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

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