Effects of 2,4-dihydroxybutyrate on lipogenesis in rat hepatocytes.
Hepatocytes were prepared from rats fasted 2 days and refed a high carbohydrate diet for 1 day. These cells contained very high levels of glycogen (about half the defatted dry weight) and carried out high rates of lipogenesis (up to 800 micron at tritium incorporation from 3HOH/g (defatted dry weight)/h), even in the absence of added substrates. Pentose cycle flux was estimated by a method involving the use of [1-14C]galactose (Rognstad, R. (1976) Int. J. Biochem. 7, 221-228). In hepatocytes from normal fasted refed rats, the amount of NADPH produced by the pentose cycle was sufficient for about one-half to three-fourths of that required for fatty acid synthesis. 2,4-Dihydroxybutyrate, a malic enzyme inhibitor (Schimerlik, M.I. & Cleland, W.W. (1977) Biochemistry 16, 565-570) markedly depressed the randomization of 14C in lactate from [6-14C]hexoses, indicating an inhibition of the pyruvate cycle. 2,4-Dihydroxybutyrate (10 mM) had only a slight inhibitory effect on overall lipogenesis, but increased the rate of the pentose cycle by 40 to 90%.
D000818:Animals; D002072:Butylene Glycols; D002087:Butyrates; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006885:Hydroxybutyrates / Q000494:pharmacology*; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D010429:Pentoses / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats
D002072:Butylene Glycols; D002087:Butyrates; D006885:Hydroxybutyrates; D007773:Lactates; D008055:Lipids; D008112:Liver Glycogen; D010429:Pentoses; D011773:Pyruvates; C021996:2,4-dihydroxybutyrate; D005947:Glucose; D005690:Galactose