Properties and organ distribution of ATP citrate (pro-3S)-lyase.
1. The lipogenic enzyme ATP citrate lyase (ATP:citrate oxaloacetate-lyase (pro-3S-CH2COO-acetyl-CoA; ATP-dephosphorylating), EC 4.1.3.8) is partially purified from human liver by ammonium sulfate fractionation and anionexchange chromatography. 2. Km values for the substrates are 1.1 x 10(-5) 1.3 x 10(-3), and 1.2 x 10(-4) M for CoASH, ATP and citrate, respectively. The hypolipidemic drug L(-)-hydroxycitrate is a competitive inhibitor with respect to citrate (Ki = 3 x 10(-4) M). 3. Specific activities measured in liver, adipose tissue and intestinal mucosa (autopsic and biopsic material) are in the range of 1 mU/mg protein suggesting that the citrate pathway does not significantly contribute to human lipogenesis. No stimulation is found after a 3-day carbohydrate-rich diet. 4. Specific activities of other key-enzymes of the acetyl-CoA production from carbohydrates (pyruvate dehydrogenase, cytosolic acetyl-CoA synthetase) are of the same low magnitude.
D001275:ATP Citrate (pro-S)-Lyase / Q000032:analysis* / Q000302:isolation & purification; D000273:Adipose Tissue / Q000201:enzymology; D000328:Adult; D000368:Aged; D000818:Animals; D001706:Biopsy; D002645:Chickens; D005227:Fatty Acids / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D014018:Tissue Distribution
D005227:Fatty Acids; D011768:Pyruvate Dehydrogenase Complex; D001275:ATP Citrate (pro-S)-Lyase