Rat ATP citrate-lyase. Molecular cloning and sequence analysis of a full-length cDNA and mRNA abundance as a function of diet, organ, and age.

Elshourbagy, Nabil A.; Near, Joseph C.; Kmetz, P; Sathe, Ganesh M.; Southan, Christopher; Strickler, J. Rudi; Gross, Mitchell; Young, James F.; Wells, Timothy N.C.; Groot, P.H.E.

doi:10.1016/s0021-9258(19)40033-1

Cited by 119 publications

(13 citation statements)

References 40 publications

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“…Accordingly, catalysis at one active site may be promoted by transformations that result from conformational changes on the same or adjacent subunits producing transient asym-metries in the configuration of otherwise identical subunits. An enzyme, structurally similar to ATP-citrate lyase, succinyl-CoA synthetase (Elshourbagy et al, 1990), appears to operate via alternating sites that are catalytically cooperative (Wolodko, 1983). CL, though possibly possessing the requisites to operate similarly, has not been shown to rapidly regulate its activity via any mechanism including phosphorylation or allosterism.…”

Section: Discussionmentioning

confidence: 99%

“…CL activity varies with changing hormonal and metabolic states (Singh et al, 1976;Gibson et al, 1972;Mackall et al, 1976;Sul et al, 1984). These activity changes, which take hours to occur, are due to changes in amounts of enzyme (Elshourbagy et al, 1990) which is regulated at transcription by the effects of nutrients and hormones (Kim et al, 1992). In addition to CL being regulatory in long-term control of lipid synthesis, it also could be important in its short-term regulation, along with acetyl-CoA carboxylase (ACC)1 (EC 6.4.1.2) activity which is regulated by both allosteric effectors and phosphorylation (Hardie, 1989).…”

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confidence: 99%

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Effect of Oxaloacetate and Phosphorylation on ATP-Citrate Lyase Activity

Pentyala

Benjamin²

1995

Biochemistry

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ATP-citrate lyase (CL) catalyzes the conversion of citrate and CoA to oxaloacetate (OA) and acetyl-CoA. As the coupled malic dehydrogenase (MDH) assay is not able either to study the effect of oxaloacetate (OA) on CL activity or to measure accurately CL activity in biological samples, a new assay was developed. The CL-citrate coupled CAT assay measures the amount of acetyl-CoA formed by transferring radiolabeled acetyl-CoA synthesized from [14C]citrate to chloramphenicol with chloramphenicol acetyltransferase (CAT). Employing this assay, the rate of increase in acetyl-CoA synthesis from citrate is linear with respect to added CL. Kinetic values for ATP, CoA and citrate are similar to those obtained using the MDH assay. The effect of CL phosphorylation on enzyme activity was determined. CL phosphorylated by cAMP-dependent protein kinase or by this kinase and glycogen synthase kinase-3 (GSK-3) decreases the apparent Vmax without changing the apparent Km. The effect of OA, a product of the enzyme reaction, on CL activity was also determined. Computational analysis of the data obtained without added OA and at three concentrations of OA indicate that the apparent Km for the substrate is not altered even though the apparent Vmax is decreased. The effect of OA on the activity of phosphorylated enzyme was also determined. OA decreases the apparent Vmax of the phosphorylated enzyme to the same extent as in control CL. This assay is able to measure CL activity in cytosol from 3T3-L1 adipocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Effect of Oxaloacetate and Phosphorylation on ATP-Citrate Lyase Activity

Pentyala

Benjamin²

1995

Biochemistry

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“…Citrate synthase catalyzes the key step in which acetyl-CoA is shuttled into the citric acid cycle. ATP-citrate lyase, which catalyzes the same aldol reaction as citrate synthase but functions in the opposite direction, controls the amount of cytosolic acetate available for fatty acid biosynthesis . Thiolase is a key enzyme in steroid biosynthesis and fatty acid biosynthesis and degradation .…”

Section: Claisen Enzymesmentioning

confidence: 99%

Coenzyme A Analogues and Derivatives: Synthesis and Applications as Mechanistic Probes of Coenzyme A Ester-Utilizing Enzymes

Mishra

Drueckhammer

2000

Chem. Rev.

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“…Rat ACL gene expression and protein content are increased at the transcriptional level by caloric intake and insulin, and are decreased by starvation and in diabetes mellitus (9,15). The in vivo phosphorylation of mammalian ACL also changes in response to nutrients and the hormonal milieu in cultured hepatocytes and during the differentiation of 3T3-L1 cells into adipocytes (16).…”

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confidence: 99%

Phosphorylation of Recombinant Human ATP:Citrate Lyase by cAMP-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. Allosteric Activation of ATP:Citrate Lyase by Phosphorylated Sugars

et al. 2000

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Recombinantly expressed human ATP:citrate lyase was purified from E. coli, and its kinetic behavior was characterized before and after phosphorylation. Cyclic AMP-dependent protein kinase catalyzed the incorporation of only 1 mol of phosphate per mole of enzyme homotetramer, and glycogen synthase kinase-3 incorporated an additional 2 mol of phosphate into the phosphorylated protein. Isoelectric focusing revealed that all of the phosphates were incorporated into only one of the four enzyme subunits. Phosphorylation resulted in a 6-fold increase in V(max) and the conversion of citrate dependence from sigmoidal, displaying negative cooperativity, to hyperbolic. The phosphorylated recombinant enzyme is more similar to the enzyme isolated from mammalian tissues than unphosphorylated enzyme with respect to the K(m) for citrate, CoA, and ATP, and the specific activity. Fructose 6-phosphate was found to be a potent activator (60-fold) of the unphosphorylated recombinant enzyme, with half-maximal activation at 0.16 mM, which results in a decrease in the apparent K(m) for citrate and ATP, as well as an increase in the V(max) of the reaction. Thus, human ATP:citrate lyase activity is regulated in vitro allosterically by phosphorylated sugars as well as covalently by phosphorylation.

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Rat ATP citrate-lyase. Molecular cloning and sequence analysis of a full-length cDNA and mRNA abundance as a function of diet, organ, and age.

Cited by 119 publications

References 40 publications

Effect of Oxaloacetate and Phosphorylation on ATP-Citrate Lyase Activity

Effect of Oxaloacetate and Phosphorylation on ATP-Citrate Lyase Activity

Coenzyme A Analogues and Derivatives: Synthesis and Applications as Mechanistic Probes of Coenzyme A Ester-Utilizing Enzymes

Phosphorylation of Recombinant Human ATP:Citrate Lyase by cAMP-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. Allosteric Activation of ATP:Citrate Lyase by Phosphorylated Sugars

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