Modeling the Negative Feedback Mechanism in the Enzyme Carboxyltransferase

2011 ◽  
Author(s):  
Xiaoyu Cai ◽  
Marcio de Queiroz ◽  
Glen Meades ◽  
Grover Waldrop
Keyword(s):  
Fatty Acid ◽  
Negative Feedback ◽  
Acid Synthesis ◽  
Feedback Mechanism ◽  
Mass Action ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Mass Action Kinetics ◽  
E Coli ◽  
Negative Feedback Mechanism

The enzyme acetyl-CoA carboxylase catalyzes the first committed step in fatty acid synthesis in all organisms. The E. coli form of the carboxyltransferase subunit was recently found to regulate its own activity and expression by binding its own mRNA. By binding acetyl-CoA or the mRNA encoding its own subunits, Carboxyltransferase is able to sense the metabolic state of the cell and attenuate its own translation and enzymatic activity using a negative feedback mechanism. In this paper, this network of interactions is modeled mathematically using mass action kinetics. Numerical simulations of the model show agreement with experimental results.

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

scholarly journals Regulation of fatty acid synthesis and malonyl-CoA content in mouse brown adipose tissue in response to cold-exposure, starvation or re-feeding

1987 ◽  
Vol 243 (2) ◽  
pp. 437-442 ◽  
Author(s):  
M G Buckley ◽  
E A Rath
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Fatty Acid Synthesis ◽  
Cold Exposure ◽  
Acid Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Malonyl Coa ◽  
Brown Adipose

1. The effect of nutritional status on fatty acid synthesis in brown adipose tissue was compared with the effect of cold-exposure. Fatty acid synthesis was measured in vivo by 3H2O incorporation into tissue lipids. The activities of acetyl-CoA carboxylase and fatty acid synthetase and the tissue concentrations of malonyl-CoA and citrate were assayed. 2. In brown adipose tissue of control mice, the tissue content of malonyl-CoA was 13 nmol/g wet wt., higher than values reported in other tissues. From the total tissue water content, the minimum possible concentration was estimated to be 30 microM 3. There were parallel changes in fatty acid synthesis, malonyl-CoA content and acetyl-CoA carboxylase activity in response to starvation and re-feeding. 4. There was no correlation between measured rates of fatty acid synthesis and malonyl-CoA content and acetyl-CoA carboxylase activity in acute cold-exposure. The results suggest there is simultaneous fatty acid synthesis and oxidation in brown adipose tissue of cold-exposed mice. This is probably effected not by decreases in the malonyl-CoA content, but by increases in the concentration of free long-chain fatty acyl-CoA or enhanced peroxisomal oxidation, allowing shorter-chain fatty acids to enter the mitochondria independent of carnitine acyltransferase (overt form) activity.

scholarly journals RNA-seq reveals novel mechanistic targets of withaferin A in prostate cancer cells

2020 ◽  
Vol 41 (6) ◽  
pp. 778-789 ◽  
Author(s):  
Su-Hyeong Kim ◽  
Eun-Ryeong Hahm ◽  
Krishna B Singh ◽  
Sruti Shiva ◽  
Jacob Stewart-Ornstein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Acid Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Rna Seq ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase

Abstract Withaferin A (WA) is a promising phytochemical exhibiting in vitro and in vivo anticancer activities against prostate and other cancers, but the mechanism of its action is not fully understood. In this study, we performed RNA-seq analysis using 22Rv1 human prostate cancer cell line to identify mechanistic targets of WA. Kyoto Encyclopedia of Genes and Genomes pathway analysis of the differentially expressed genes showed most significant enrichment of genes associated with metabolism. These results were validated using LNCaP and 22Rv1 human prostate cancer cells and Hi-Myc transgenic mice as models. The intracellular levels of acetyl-CoA, total free fatty acids and neutral lipids were decreased significantly following WA treatment in both cells, which was accompanied by downregulation of mRNA (confirmed by quantitative reverse transcription-polymerase chain reaction) and protein levels of key fatty acid synthesis enzymes, including ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A. Ectopic expression of c-Myc, but not constitutively active Akt, conferred a marked protection against WA-mediated suppression of acetyl-CoA carboxylase 1 and fatty acid synthase protein expression, and clonogenic cell survival. WA was a superior inhibitor of cell proliferation and fatty acid synthesis in comparison with known modulators of fatty acid metabolism including cerulenin and etomoxir. Intraperitoneal WA administration to Hi-Myc transgenic mice (0.1 mg/mouse, three times/week for 5 weeks) also resulted in a significant decrease in circulating levels of total free fatty acids and phospholipids, and expression of ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A proteins in the prostate in vivo.

scholarly journals Chronic ethanol administration depresses fatty acid synthesis in rat adipose tissue

1988 ◽  
Vol 251 (2) ◽  
pp. 547-551 ◽  
Author(s):  
J S Wilson ◽  
M A Korsten ◽  
L P Donnelly ◽  
P W Colley ◽  
J B Somer ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Fatty Acid Synthetase ◽  
Acid Synthesis ◽  
Chronic Ethanol ◽  
Ethanol Administration ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Chronic Ethanol Administration

Administration of ethanol as part of a nutritionally adequate liquid diet to female Wistar rats was found to depress markedly incorporation of labelled glucose into adipose-tissue acylglycerol fatty acids. Similar results with labelled pyruvate and acetate suggested inhibition of the fatty-acid-synthesis pathway at, or distal to, the acetyl-CoA carboxylase step. Activities of acetyl-CoA carboxylase and fatty acid synthetase were markedly lower in ethanol-fed animals. The activity of another lipogenic enzyme, phosphatidate phosphohydrolase, was not affected by chronic ethanol feeding. These findings suggest that chronic ethanol administration has marked effects on adipose-tissue lipogenesis.

scholarly journals Stimulation of hepatic lipogenesis and acetyl-coenzyme A carboxylase by vasopressin

1981 ◽  
Vol 198 (3) ◽  
pp. 485-490 ◽  
Author(s):  
F Assimacopoulos-Jeannet ◽  
R M Denton ◽  
B Jeanrenaud
Keyword(s):  
Fatty Acid ◽  
Dose Response ◽  
Fatty Acid Synthesis ◽  
Response Curve ◽  
Acid Synthesis ◽  
Dose Response Curve ◽  
Dependent Manner ◽  
Hepatic Lipogenesis ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa

The effect of vasopressin on the short-term regulation of fatty acid synthesis was studied in isolated hepatocytes from rats fed ad libitum. Vasopressin stimulates fatty acid synthesis by 30-110%. This increase is comparable with that obtained with insulin. Angiotensin also stimulates fatty acid synthesis, whereas phenylephrine does not. The dose-response curve for vasopressin-stimulated lipogenesis is similar to the dose-response curve for glycogenolysis and release of lactate plus pyruvate. Vasopression also stimulates acetyl-CoA carboxylase activity in a dose-dependent manner. Vasopressin does not relieve glucagon-inhibited lipogenesis, whereas insulin does. The action of vasopressin on hepatic lipogenesis is decreased, but not suppressed, in Ca2+-depleted hepatocytes. The results suggest that vasopressin acts on lipogenesis by increasing availability of lipogenic substrate (lactate + pyruvate) and by activating acetyl-CoA carboxylase.

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.

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