scholarly journals Glucagon inhibits fatty acid synthesis in isolated hepatocytes via phosphorylation of acetyl-CoA carboxylase by cyclic-AMP-dependent protein kinase

1984 ◽  
Vol 140 (2) ◽  
pp. 325-333 ◽  
Author(s):  
Ross HOLLAND ◽  
Lee A. WITTERS ◽  
D. Grahame HARDIE
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Isolated Hepatocytes ◽  
Acetyl Coa Carboxylase ◽  
Dependent Protein Kinase ◽  
Acetyl Coa ◽  
Dependent Protein

Regulation of mammalian acetyl-CoA carboxylase

2002 ◽  
Vol 30 (6) ◽  
pp. 1059-1064 ◽  
Author(s):  
M. R. Munday
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Critical Role ◽  
Physiological Role ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Dependent Protein ◽  
Amp Activated Protein Kinase

Acetyl-CoA carboxylase (ACC) plays a critical role in the regulation of fatty acid metabolism and its two isoforms, ACCα and ACCβ, appear to have distinct functions in the control of fatty acid synthesis and fatty acid oxidation, respectively. They are regulated by similar short-term mechanisms of allosteric activation by citrate, and reversible phosphorylation and inactivation, and there is clearly interaction between these mechanisms. AMP-activated protein kinase is the important physiological ACC kinase for both isoforms and yet there is a potential physiological role for cAMP-dependent protein kinase in the hormonally mediated inactivation of ACCα, and phosphorylation of ACCβ in its unique N-terminus.

scholarly journals Glucagon regulates ACC activity in adipocytes through the CAMKKβ/AMPK pathway

2012 ◽  
Vol 302 (12) ◽  
pp. E1560-E1568 ◽  
Author(s):  
I-Chen Peng ◽  
Zhen Chen ◽  
Wei Sun ◽  
Ying-Shiuan Li ◽  
Traci LaNai Marin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Protein Kinase ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Dependent Protein Kinase ◽  
Ampk Signaling ◽  
Dependent Protein

Glucagon is important for regulating lipid metabolism in part through its inhibition of fatty acid synthesis in adipocytes. Acetyl-CoA carboxylase 1 (ACC1) is the rate-limiting enzyme for fatty acid synthesis. Glucagon has been proposed to activate cAMP-dependent protein kinase A (PKA), which phosphorylates ACC1 to attenuate the lipogenic activity of ACC1. Because AMP-activated protein kinase (AMPK) also inhibits fatty acid synthesis by phosphorylation of ACC1, we examined the involvement of AMPK and its upstream kinase in the glucagon-elicited signaling in adipocytes in vitro and in vivo. LC-MS-MS analysis suggested that ACC1 was phosphorylated only at Ser79, an AMPK-specific site, in glucagon-treated adipocytes. Pharmacological inhibitors and siRNA knockdown of AMPK or PKA in adipocytes demonstrate that glucagon regulates ACC1 and ACC2 activity through AMPK but not PKA. By using Ca2+/calmodulin-dependent protein kinase kinase-β knockout (CaMKKβ−/−) mice and cultured adipocytes, we further show that glucagon activates the CaMKKβ/AMPK/ACC cascade. Additionally, fasting increases the phosphorylation of AMPK and ACC in CaMKKβ+/+ but not CaMKKβ−/− mice. These results indicate that CaMKKβ/AMPK signaling is an important molecular component in regulating lipid metabolism in adipocytes responding to glucagon and could be a therapeutic target for the dysregulation of energy storage.

scholarly journals Use of rapid gel-permeation chromatography to explore the inter-relationships between polymerization, phosphorylation and activity of acetyl-CoA carboxylase. Effects of insulin and phosphorylation by cyclic AMP-dependent protein kinase

1987 ◽  
Vol 241 (3) ◽  
pp. 773-782 ◽  
Author(s):  
A C Borthwick ◽  
N J Edgell ◽  
R M Denton
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Degree Of Polymerization ◽  
Beta Agonist ◽  
Epididymal Adipose Tissue ◽  
Acetyl Coa Carboxylase ◽  
Dependent Protein Kinase ◽  
Acetyl Coa ◽  
Polymeric Form ◽  
Dependent Protein

Superose 6 chromatography was used to separate rapidly the polymeric and dimeric forms of acetyl-CoA carboxylase. With preparations of acetyl-CoA carboxylase purified by Sepharose-avidin chromatography, it is shown that citrate promotes polymerization and that the extent of polymerization is diminished, but not eliminated, after phosphorylation by cyclic-AMP-dependent protein kinase. After exposure of rat epididymal adipose tissue to insulin, evidence was obtained for a marked increase in polymerization. The polymeric form, which was active in the absence of citrate, exhibited increased phosphorylation, particularly on a tryptic peptide designated the I-peptide in an earlier study [Brownsey & Denton (1982) Biochem. J. 202, 77-86]. In contrast, in tissue exposed to the beta-agonist isoprenaline, most of the phosphorylated acetyl-CoA carboxylase appeared to be in the dimeric form if chromatography was carried out in the absence of citrate, whereas in the presence of citrate the degree of polymerization was diminished.

scholarly journals Evidence that glucagon-mediated inhibition of acetyl-CoA carboxylase in isolated adipocytes involves increased phosphorylation of the enzyme by cyclic AMP-dependent protein kinase

1985 ◽  
Vol 226 (1) ◽  
pp. 139-145 ◽  
Author(s):  
R Holland ◽  
D G Hardie ◽  
R A Clegg ◽  
V A Zammit
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Kinetic Parameters ◽  
Acetyl Coa Carboxylase ◽  
Response Curves ◽  
Dependent Protein Kinase ◽  
Acetyl Coa ◽  
Dependent Protein ◽  
Isolated Adipocytes

The kinetic parameters and phosphorylation state of acetyl-CoA carboxylase were analysed after purification of the enzyme by avidin-Sepharose chromatography from extracts of isolated adipocytes treated with glucagon or adrenaline. The results provide evidence that the mechanism of inhibition of acetyl-CoA carboxylase in adipocytes treated with glucagon [Zammit & Corstorphine (1982) Biochem. J. 208, 783-788] involves increased phosphorylation of the enzyme. Hormone treatment had effects on the kinetic parameters of the enzyme similar to those of phosphorylation of the enzyme in vitro by cyclic AMP-dependent protein kinase. Glucagon treatment of adipocytes led to increased phosphorylation of acetyl-CoA carboxylase in the same chymotryptic peptide as that containing the major site phosphorylated on the enzyme by purified cyclic AMP-dependent protein kinase in vitro [Munday & Hardie (1984) Eur. J. Biochem. 141, 617-627]. The dose-response curves for inhibition of enzyme activity and increased phosphorylation of the enzyme were very similar, with half-maximal effects occurring at concentrations of glucagon (0.5-1 nM) which are close to the physiological range. In general, the patterns of increased 32P-labelling of chymotryptic peptides induced by glucagon or adrenaline were similar, although there were quantitative differences between the effects of the two hormones on individual peptides. The results are discussed in terms of the possible roles of cyclic AMP-dependent and -independent protein kinases in the regulation of acetyl-CoA carboxylase activity and of lipogenesis in white adipose tissue.

scholarly journals HFA1 Encoding an Organelle-specific Acetyl-CoA Carboxylase Controls Mitochondrial Fatty Acid Synthesis inSaccharomyces cerevisiae

2004 ◽  
Vol 279 (21) ◽  
pp. 21779-21786 ◽  
Author(s):  
Ursula Hoja ◽  
Sandra Marthol ◽  
Jörg Hofmann ◽  
Sabine Stegner ◽  
Rainer Schulz ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Mitochondrial Fatty Acid
Sign in / Sign up

Export Citation Format

Share Document