The metabolic fate of the products of citrate cleavage. Adenosine triphosphate-citrate lyase and nicotinamide-adenine dinucleotide phosphate-linked malate dehydrogenase in foetal and adult liver from ruminants and non-ruminants.
1. Foetal rat liver slices incorporate the C-3 of aspartate and C-2 of glutamate into fatty acids at rates equal to those observed with adult rat liver slices. Incorporation of either of these labelled carbon atoms into fatty acids would require a functioning citrate-cleavage pathway which consists of the enzymes ATP-citrate lyase, NAD-malate dehydrogenase and NADP-malate dehydrogenase. However, NADP-malate dehydrogenase is present in foetal rat liver at only 5% of the activity detectable in adult rat liver. 2. From these findings and the effect of cofactors on the formation of (14)CO(2) from [1,5-(14)C(2)]citrate in liver supernatant fractions (100000g), it is suggested that NADP-malate dehydrogenase limits the citrate-cleavage sequence. 3. Measurement of the citrate-cleavage pathway by incorporation studies with [3-(14)C]aspartate and [U-(14)C]glucose and by determining the activities of ATP-citrate lyase and NADP-malate dehydrogenase have shown that this sequence of reactions is present in the liver of the bovine foetus but not in the adult. However, C-2 of glutamate is not incorporated into fatty acids or non-saponifiable lipid by bovine liver slices. This finding as well as those presented above for the adult and foetal rat liver are interpreted on the basis of a competition between phosphoenolpyruvate carboxykinase and NAD-malate dehydrogenase for oxaloacetate produced by the cleavage of citrate in the cytosol.
D000255:Adenosine Triphosphate; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes; D002417:Cattle; D002951:Citrates / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis; D005260:Female; D005333:Fetus / Q000201:enzymology*; D005947:Glucose / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D066298:In Vitro Techniques; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development / Q000378:metabolism; D008190:Lyases / Q000378:metabolism*; D008291:Malate Dehydrogenase; D008297:Male; D009243:NAD; D009249:NADP; D011247:Pregnancy; D051381:Rats
D002247:Carbon Isotopes; D002951:Citrates; D005227:Fatty Acids; D005971:Glutamates; D008055:Lipids; D009243:NAD; D002245:Carbon Dioxide; D001224:Aspartic Acid; D009249:NADP; D000255:Adenosine Triphosphate; D008291:Malate Dehydrogenase; D008190:Lyases; D005947:Glucose