Alpha-keto acid metabolism by hepatocytes cultured in a hybrid liver support bioreactor.
Isolated pig liver cells cultured using a perfusion technique were analyzed over 39 days to test their ability to change the perfusate alpha-keto acid profile. While the pyruvate concentration in the culture medium decreased as of the first day, the alpha-ketoglutarate (KG), alpha-ketoisocaproate (KIC), alpha-ketoisovalerate (KIV) and alpha-keto-beta-methyl-n-valerate (KMV) were synthesized immediately and released by the liver cells. The metabolic capacity of the cell culture system increased up to day 10, decreased during the following 5 days and reached a steady state beyond day 15, which was maintained for at least 30 days. The branched chain alpha-keto acid release, in particular alpha-ketoisocaproate, reflects an effective transamination capacity of the newly developed culture system and shows an intact protein biosynthesis for at least 30 days in vitro.
Fuchs
M
M
Institut für Biochemie, Freie Universität Berlin, Germany.
Gerlach
J
J
Unger
J
J
Encke
J
J
Smith
M
M
Neuhaus
P
P
Nündel
M
M
Riedel
E
E
D000818:Animals; D001187:Artificial Organs; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D045782:Hemiterpenes; D007651:Keto Acids / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008111:Liver Function Tests; D010477:Perfusion; D011188:Potassium / Q000378:metabolism; D014176:Protein Biosynthesis; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D013552:Swine
D045782:Hemiterpenes; D007651:Keto Acids; D007656:Ketoglutaric Acids; D011773:Pyruvates; C016211:alpha-keto-beta-methylvaleric acid; C001505:alpha-ketoisovalerate; C013082:alpha-ketoisocaproic acid; D019289:Pyruvic Acid; D003577:Cytochrome P-450 Enzyme System; D011188:Potassium