Hormonal regulation of acetyl-CoA carboxylase in epididymal adipose tissue

1. Most of the cyclic-nucleotide-independent acetyl-CoA carboxylase kinase activity in an extract of rat epididymal adipose tissue was evaluated from a Mono Q column by 0.175 M-NaCl at pH 7.4. The activity of the kinase in this fraction (fraction 1) was increased after exposure of intact tissue to insulin. 2. Incubation of purified adipose-tissue acetyl-CoA carboxylase with [gamma-32P]ATP and samples of fraction 1 led to the incorporation of up to 0.4 mol of 32P/mol of enzyme subunit. Most of the phosphorylation was on serine residues within a single tryptic peptide. This peptide, on the basis of two-dimensional t.l.c. analysis, h.p.l.c. and Superose 12 chromatography, appeared to be the same as the acetyl-CoA carboxylase peptide (‘I’-peptide) which exhibits increased phosphorylation in insulin-treated tissue. 3. Phosphorylation of purified acetyl-CoA carboxylase by the kinase in fraction 1 was found to be associated with a parallel 4-fold increase in activity. However, increases in both phosphorylation and activity were much diminished if fraction 1 was treated by Centricon centrifugation to remove low-Mr components. Among these components was a potent inhibitor of acetyl-CoA carboxylase activity which appeared to be necessary for the kinase in fraction 1 to be fully active. 4. The inhibitor remains to be identified, but inhibition requires MgATP, although the inhibitor itself does not cause any phosphorylation of the carboxylase. No effects of insulin were observed on the activity of the inhibitor. 5. It is concluded that the kinase probably plays an important role in the mechanism whereby insulin brings about the well-established increases in phosphorylation and activation of acetyl-CoA carboxylase in adipose tissue.

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Acute effects in vivo of anti-insulin serum on rates of fatty acid synthesis and activities of acetyl-coenzyme A carboxylase and pyruvate dehydrogenase in liver and epididymal adipose tissue of fed rats

Biochemical Journal ◽

10.1042/bj1600413 ◽

1976 ◽

Vol 160 (2) ◽

pp. 413-416 ◽

Cited By ~ 196

Author(s):

D Stansbie ◽

R W Brownsey ◽

M Crettaz ◽

R M Denton

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Fatty Acid Synthesis ◽

Pyruvate Dehydrogenase ◽

Acid Synthesis ◽

Epididymal Adipose Tissue ◽

Acetyl Coa Carboxylase ◽

Acetyl Coa ◽

Carboxylase Activity

Plasma insulin concentrations in fed rats were altered acutely by administration of glucose or anti-insulin serum. Rates of fatty acid synthesis in adipose tissue and liver were estimated from the incorporation of 3H from 3H2O. In the adipose tissue dehydrogenase and acetyl-CoA carboxylase were evident. In liver, although changes in rates of fatty acid synthesis were found, the initial activity of pyruvate dehydrogenase did not alter, but small parallel changes in acetyl-CoA carboxylase activity were observed.

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Rat epididymal adipose tissue acetyl-CoA carboxylase

Canadian Journal of Biochemistry ◽

10.1139/o70-143 ◽

1970 ◽

Vol 48 (8) ◽

pp. 915-921 ◽

Cited By ~ 6

Author(s):

P. R. Desjardins ◽

K. Dakshinamurti

Keyword(s):

Adipose Tissue ◽

Epididymal Adipose Tissue ◽

Acetyl Coa Carboxylase ◽

Acetyl Coa ◽

Ph Optimum ◽

Epididymal Fat ◽

Ph Dependent ◽

Rat Adipose Tissue ◽

Cold Inactivation ◽

Fat Pads

The properties of a partially purified acetyl-CoA carboxylase (acetyl-CoA:CO2 ligase (ADP), EC 6.4.1.2) from rat epididymal fat pads have been studied. The properties of the rat adipose tissue enzyme are similar to those of the liver in regard to the pH optimum and affinity for substrates and inhibitors. The rat adipose tissue carboxylase shows a pH-dependent, reversible cold inactivation.

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Adrenaline and the regulation of acetyl-coenzyme A carboxylase in rat epididymal adipose tissue. Inactivation of the enzyme is associated with phosphorylation and can be reversed on dephosphorylation

Biochemical Journal ◽

10.1042/bj1840023 ◽

1979 ◽

Vol 184 (1) ◽

pp. 23-32 ◽

Cited By ~ 55

Author(s):

R W Brownsey ◽

W A Hughes ◽

R M Denton

Keyword(s):

Adipose Tissue ◽

Metal Ion ◽

Potassium Citrate ◽

Epididymal Adipose Tissue ◽

Kinetic Properties ◽

Fat Cells ◽

Acetyl Coa Carboxylase ◽

Acetyl Coa ◽

Carboxylase Activity ◽

Cell Extracts

1. Exposure of rat epididymal fat-pads or isolated fat-cells to adrenaline results in a decrease in acetyl-CoA carboxylase activity measured both in initial extracts and in extracts incubated with potassium citrate; in addition the concentration of citrate required to give half-maximal activation may also be increased. 2. Incorporation of 32Pi into acetyl-CoA carboxylase within intact fat-cells was investigated and evidence is presented that adrenaline increases the extent of phosphorylation of the enzyme. 3. Dephosphorylation of 32P-labelled acetyl-CoA carboxylase was studied in cell extracts. The rate of release of 32P is increased by 5mM-MgCl2 plus 10–100 microM-Ca2+, whereas it is inhibited by the presence of bivalent metal ion chelators such as EDTA and citrate. 4. The effects of adrenaline on the kinetic properties of acetyl-CoA carboxylase disappear if pad or cell extracts are treated with Mg2+ and Ca2+ under conditions that also lead to dephosphorylation of the enzyme. 5. The results of this study represent convincing evidence that adrenaline inactivates acetyl-CoA carboxylase in adipose-tissue preparations by increasing the degree of phosphorylation of the enzyme.

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Growth-hormone-prolactin interactions in the regulation of mammary and adipose-tissue acetyl-CoA carboxylase activity and gene expression in lactating rats

Biochemical Journal ◽

10.1042/bj2850469 ◽

1992 ◽

Vol 285 (2) ◽

pp. 469-475 ◽

Cited By ~ 27

Author(s):

M C Barber ◽

M T Travers ◽

E Finley ◽

D J Flint ◽

R G Vernon

Keyword(s):

Adipose Tissue ◽

Mammary Gland ◽

Serum Prolactin ◽

Acetyl Coa Carboxylase ◽

Acetyl Coa ◽

Carboxylase Activity ◽

Total Enzyme Activity ◽

Mrna Concentration ◽

Total Enzyme ◽

Activation Status

The factors and mechanisms responsible for the reciprocal changes in lipogenesis in rat mammary gland and adipose tissue during the lactation cycle have been investigated. Lactation decreased the activation status and mRNA concentration of acetyl-CoA carboxylase in adipose tissue. Litter removal decreased the mRNA concentration of acetyl-CoA carboxylase in the mammary gland and increased the enzyme's mRNA concentration and activation status in adipose tissue. Lowering serum prolactin concentration in lactating rats decreased the amount of mammary acetyl-CoA carboxylase mRNA and increased that of adipose tissue, and increased the activation status of the enzyme in adipose tissue. Decreasing serum growth hormone (GH) alone had little effect on acetyl-CoA carboxylase in lactating rats, although it did lower pup growth rate and serum concentration of insulin-like growth factor-I. Lowering serum GH concentration exacerbated the effects of decreasing serum prolactin on mammary-gland (but not adipose-tissue) acetyl-CoA carboxylase mRNA and further increased the rise in activation status of the adipose-tissue enzyme induced by decreasing serum prolactin. Changes in acetyl-CoA carboxylase mRNA in both mammary and adipose tissue were paralleled by changes in total enzyme activity except after litter removal, when there was a disproportionately large decrease in total enzyme activity of the mammary gland. Thus prolactin has a major and GH a minor role in the regulation of acetyl-CoA carboxylase activity during lactation. Changes in mammary activity in response to prolactin and GH are primarily due to alterations in gene transcription, whereas adaptation in adipose tissue involves both changes in gene transcription and activation status.

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