Fructose-associated hepatotoxicity indexed by the lactate dehydrogenase isoenzyme LDH-5

Autor: Basant K. Puri, Michele C. Kingston, Jean A. Monro
Rok vydání: 2018
Předmět:
Zdroj: Medical hypotheses. 124
ISSN: 1532-2777
Popis: Modern diets have become increasingly rich in fructose, for example through the addition of high-fructose corn syrup to many foods and drinks. It has been suggested that this might lead to hepatotoxicity, including the development of non-alcoholic fatty liver disease. After entering hepatocytes via insulin-independent glucose transporter 2 transmembrane carrier proteins, fructose is phosphorylated to fructose-1-phosphate in a reaction catalysed by fructokinase (ketohexokinase). In turn, fructose-1-phosphate is hydrolysed by aldolase B to glyceraldehydes. Glyceraldehydes may enter gluconeogenesis via fructose-1,6-bisphosphate and fructose-6-phosphate; glyceraldehydes may also enter glycogenolysis via pyruvate. The last pathway involves conversion of pyruvate to acetyl-CoA. Alternatively, pyruvate may be converted, via the action of the hepatic lactate dehydrogenase isoenzyme LDH-5, into lactate. In liver damage, the LDH-5 isoenzyme becomes elevated, predominantly in serum/plasma. We therefore hypothesised that if dietary fructose is associated with hepatotoxicity, there should be a positive correlation between erythrocyte fructose-6-phosphate and plasma LDH-5. This hypothesis was tested by assaying venous blood samples taken from 39 patients at rest, three hours after eating. Quantitative Fourier transform infrared spectrometry following gel electrophoresis was used to assay erythrocyte fructose-6-phosphate levels. Similarly, plasma LDH-5 concentrations were spectrophotometrically analysed, using the pyruvate-lactate reaction, following electrophoretic separation of the LDH isoenzymes. A significant positive correlation was found between the two variables (r = 0.44, p = 0.0047). This result, which supports our hypothesis, is evidence in favour of the possibility that dietary fructose is associated with hepatotoxicity. In addition to being a marker of hepatic damage, LDH-5 may play a more direct epigenetic role in causing liver damage; acute hepatic injury is associated with nuclear translocation of LDH, causing the production of lactate from pyruvate in the nucleus; in turn, the lactate inhibits histone deacetylase and is associated with upregulation of genes associated with the damage response, leading to cell death.
Databáze: OpenAIRE
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