Effects of alanine aminotransferase inhibition on the intermediary metabolism in Sparus aurata through dietary amino-oxyacetate supplementation.
In liver, through the reaction catalysed by alanine aminotransferase (ALT), alanine becomes an effective precursor for gluconeogenesis. In the present study amino-oxyacetate (AOA) was used to evaluate its effect on liver ALT activity of the carnivorous fish Sparus aurata. Moreover, the derived metabolic effects on metabolites and other key enzymes of glycolysis, gluconeogenesis and the pentose phosphate pathway were also studied. A dose-effect-dependent inhibition of AOA on hepatic cytosolic and mitochondrial ALT activity was observed in vitro. In vivo, AOA behaved as an inhibitor of hepatic cytosolic ALT activity. A long-term exposure to AOA increased pyruvate kinase activity in the liver irrespective of the composition of the diet supplied to fish. 1H NMR studies showed that inclusion of AOA to the diet decreased the hepatic levels of alanine, glutamate and glycogen. Moreover, 2H NMR analysis indicated a higher renewal rate for alanine in the liver of fish fed with a high-carbohydrate/low-protein diet, while AOA decreased alanine 2H-enrichment irrespective of the diet. The present study indicates that AOA-dependent inhibition of the cytosolic ALT activity could help to increase the use of dietary carbohydrate nutrients.
Departament de Bioquímica i Biologia Molecular, Facultat de Farmàcia, Universitat de Barcelona, Joan XXIII s/n, 08028 Barcelona, Spain.
Juan D
JD
González
Albert
A
Caballero
Ivan
I
Viegas
Isidoro
I
Metón
John G
JG
Jones
Joana
J
Barra
Felipe
F
Fernández
Isabel V
IV
Baanante
D000409:Alanine / Q000378:metabolism; D000410:Alanine Transaminase / Q000037:antagonists & inhibitors*; D000625:Aminooxyacetic Acid / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004032:Diet; D018753:Diet, Protein-Restricted; D004040:Dietary Carbohydrates / Q000378:metabolism*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D021541:Sea Bream / Q000378:metabolism*
D004040:Dietary Carbohydrates; D000625:Aminooxyacetic Acid; D018698:Glutamic Acid; D006003:Glycogen; D000410:Alanine Transaminase; D011770:Pyruvate Kinase; D000409:Alanine