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Acetyl-CoA carboxylase inactivation

Proteins phosphorylated by cAPK include glycogen phosphorylase b kinase (activates), PFK-2 (inactivates), acetyl CoA carboxylase (inactivates), hormone-sensitive triacylglycerol lipase... [Pg.373]

The cause of acetyl-CoA carboxylase inactivation in partially purified enzyme preparations in the presence of ATP and Mg " " should he clarified at the outset. Because it has been reported that the carbox-ylated species of acetyl-CoA carboxylase is unstable and tends to de-polymerize in the absence of citrate (see Ref. 64), inactivation of acetyl-CoA carboxylase by ATP and Mg " has frequently been interpreted in terms of the formation of a carboxylated form of acetyl-CoA carboxylase 25,39, 64). According to this hypothesis, phosphorylation phenomena can be explained on the supposition that carboxylation of the enzyme results in changes in the structure of the carboxylase which make normally unavailable sites available for phosphorylation that is, phosphorylation is not the cause of enzyme inactivation, but a secondary result of carboxylation. [Pg.154]

When various tissues are treated with cyclic AMP or its derivative, dihutyryl cyclic AMP, acetyl-CoA carboxylase is inactivated, suggesting that cyclic AMP is involved in the process of acetyl-CoA carboxylase inactivation (4, 5, 12, 44, 45, 69). However, the exact site of cyclic AMP action is not clear. Lane and co-workers 124) reported that in the chicken liver cell system, cyclic AMP affects the formation of cellular citrate which in turn affects the polymeric status of the carboxylase. [Pg.167]

The effect of cyclic AMP on the phosphorylation and inactivation of the carboxylase can be duplicated by equimolar concentrations of AMP, indicating that AMP can substitute for cyclic AMP. In Fig. 10, the effect of different concentrations of AMP on the inactivation of the carboxylase is shown. The most important implication of the data presented above is that acetyl-CoA carboxylase inactivation by the endogenous kinase is affected by the signal of low energy status in the cell, i.e., AMP. [Pg.168]

Acetyl-CoA carboxylase is an allosteric enzyme and is activated by citrate, which increases in concentration in the well-fed state and is an indicator of a plentiful supply of acetyl-CoA. Citrate converts the enzyme from an inactive dimer to an active polymeric form, having a molecular mass of several milhon. Inactivation is promoted by phosphorylation of the enzyme and by long-chain acyl-CoA molecules, an example of negative feedback inhibition by a product of a reaction. Thus, if acyl-CoA accumulates because it is not esterified quickly enough or because of increased lipolysis or an influx of free fatty acids into the tissue, it will automatically reduce the synthesis of new fatty acid. Acyl-CoA may also inhibit the mitochondrial tricarboxylate transporter, thus preventing activation of the enzyme by egress of citrate from the mitochondria into the cytosol. [Pg.178]

Figure 21-6. Regulation of acetyl-CoA carboxylase by phosphorylation/dephosphorylation.The enzyme is inactivated by phosphorylation by AMP-activated protein kinase (AMPK), which in turn is phosphorylated and activated by AMP-activated protein kinase kinase (AMPKK). Glucagon (and epinephrine), after increasing cAMP, activate this latter enzyme via cAMP-dependent protein kinase. The kinase kinase enzyme is also believed to be activated by acyl-CoA. Insulin activates acetyl-CoA carboxylase, probably through an "activator" protein and an insulin-stimulated protein kinase. Figure 21-6. Regulation of acetyl-CoA carboxylase by phosphorylation/dephosphorylation.The enzyme is inactivated by phosphorylation by AMP-activated protein kinase (AMPK), which in turn is phosphorylated and activated by AMP-activated protein kinase kinase (AMPKK). Glucagon (and epinephrine), after increasing cAMP, activate this latter enzyme via cAMP-dependent protein kinase. The kinase kinase enzyme is also believed to be activated by acyl-CoA. Insulin activates acetyl-CoA carboxylase, probably through an "activator" protein and an insulin-stimulated protein kinase.
The major control point for fatty acid synthesis is acetyl-CoA carboxylase. The enzyme is inactivated by phosphorylation and activated by high concentrations of citrate. [Pg.170]

The regulation of fat metabolism is relatively simple. During fasting, the rising glucagon levels inactivate fatty acid synthesis at the level of acetyl-CoA carboxylase and induce the lipolysis of triglycerides in the adipose tissue by stimulation of a hormone-sensitive lipase. This hormone-sensitive lipase is activated by glucagon and epinephrine (via a cAMP mechanism). This releases fatty acids into the blood. These are transported to the various tissues, where they are used. [Pg.222]

Figure 7.15 Inhibition of acetyl-CoA carboxylase by cyclic AMP dependent protein kinase and AMP dependent protein kinase the dual effect of glucagon. Phosphorylation of acetyl-CoA carboxylase by either or both enzymes inactivates the enzyme which leads to a decrease in concentration of malonyl-CoA, and hence an increase in activity of carnitine palmitoyltransferase-I and hence an increase in fatty acid oxidation. Insulin decreases the cyclic AMP concentration maintaining an active carboxylase and a high level of malonyl-CoA to inhibit fatty acid oxidation. Figure 7.15 Inhibition of acetyl-CoA carboxylase by cyclic AMP dependent protein kinase and AMP dependent protein kinase the dual effect of glucagon. Phosphorylation of acetyl-CoA carboxylase by either or both enzymes inactivates the enzyme which leads to a decrease in concentration of malonyl-CoA, and hence an increase in activity of carnitine palmitoyltransferase-I and hence an increase in fatty acid oxidation. Insulin decreases the cyclic AMP concentration maintaining an active carboxylase and a high level of malonyl-CoA to inhibit fatty acid oxidation.
The key enzyme in fatty acid synthesis is acetyl CoA carboxylase (see p. 162), which precedes the synthase and supplies the malonyl-CoA required for elongation. Like all carboxylases, the enzyme contains covalently bound biotin as a prosthetic group and is hormone-dependently inactivated by phosphorylation or activated by dephosphorylation (see p. 120). The precursor citrate (see p. 138) is an allosteric activator, while palmitoyl-CoA inhibits the end product of the synthesis pathway. [Pg.168]

Additional information <1> (<1> two other cAMP-independent kinases found, that phosphorylate but do not effect acetyl-CoA carboxylase kinase activity [6] <1> phosphorylation by cAMP-dependent protein kinase has the same effect on acetyl-CoA carboxylase activity then phosphorylation with acetyl-CoA carboxylase kinase-2 [6,7] <1> cAMP-dependent protein kinase identified, that phosphorylates and inactivates acetyl-CoA carboxylase in vitro, but appears not to be involved in regulation in vivo [8]) [6-8]... [Pg.123]

Shiao, M.-S. Drong, R.F. Porter, J.W. The purification and properties of a protein kinase and the partial purification of a phosphoprotein phosphatase that inactivate and activate acetyl-CoA carboxylase. Biochem. Biophys. Res. Commun., 98, 80-87 (1981)... [Pg.127]

Lent, B.A. Kim, K.-H. Purification and properties of a kinase which phos-phorylates and inactivates acetyl-CoA carboxylase. J. Biol. Chem., 257, 1897-1901 (1982)... [Pg.127]

Ottey, K.A. Takhar, S. Munday, M.R. Comparison of two cyclic-nucleotide-independent acetyl-CoA carboxylase kinase from lactating rat mammary gland identification of the kinase responsible for acetyl-CoA inactivation in vivo. Biochem. Soc. Trans., 17, 349-350 (1989)... [Pg.127]

Acetyl-CoA carboxylase is also regulated by covalent modification. Phosphorylation, triggered by the hormones glucagon and epinephrine, inactivates the enzyme and reduces its sensitivity to activation by citrate, thereby slowing fatty acid synthesis. In its active (dephosphorylated) form, acetyl-CoA carboxylase polymerizes into long filaments (Fig. 21-1 lb) phosphorylation is accompanied by dissociation into monomeric subunits and loss of activity. [Pg.796]

One enzyme regulated by AMPK is acetyl-CoA carboxylase, which produces malonyl-CoA, the first intermediate committed to fatty acid synthesis. Malonyl-CoA is a powerful inhibitor of the enzyme carnitine acyl-transferase I, which starts the process of ]3 oxidation by transporting fatty acids into the mitochondrion (see Fig. 17-6). By phosphorylating and inactivating acetyl-CoA carboxylase, AMPK inhibits fatty acid synthesis while relieving the inhibition (by malonyl-CoA) of )3 oxidation (Fig. 23-37). [Pg.914]

The regulated step in fatty acid synthesis (acetyl CoA - malonyl CoA) is catalyzed by acetyl CoA carboxylase, which requires biotin. Citrate is the allosteric activator, and long-chain fatty acyl CoA is the inhibitor. The enzyme can also be activated in the presence of insulin and inactivated in the presence of epinephrine or glucagon. [Pg.484]

Regulation of acetyl-CoA carboxylase by phosphorylation and dephosphorylation. Glucagon is known to activate cAMP-dependent protein kinase this kinase phosphorylates both serine 77 and serine 1200 of rat acetyl-CoA carboxylase, which inactivates the enzyme. However, there is also an AMP-dependent kinase that phosphorylates serine 79 and serine 1200 and inactivates the rat acetyl-CoA carboxylase. The relative importance of these two kinases in regulating the carboxylase in vivo is still unclear. Likewise, the phosphorylated enzyme is a substrate for several different protein phosphate phosphatases, and the physiologically relevant phosphatases are not known. Epinephrine may inhibit the carboxylase via a Ca2+-dependent protein kinase. [Pg.432]

The anabolic hormone insulin has the opposite effect to glucagon and epinephrine. It stimulates the formation of triacylglycerols through decreasing the level of cAMP, which promotes the dephosphorylation and inactivation of hormone-sensitive lipase (Fig. 5). Insulin also stimulates the dephosphorylation of acetyl CoA carboxylase, thereby activating fatty acid synthesis (see Topic K3). Thus fatty acid synthesis and degradation are coordinately controlled so as to prevent a futile cycle. [Pg.331]

In addition, HMG CoA reductase, like acetyl CoA carboxylase in fatty acid synthesis (see Topic K3), is inactivated by phosphorylation by an AMP-activated protein kinase, retained in this form under the influence of glucagon during starvation. [Pg.335]

Other than hormone-sensitive lipase, only acetyl-CoA carboxylase is affected by phosphorylation, but this event is controlled by an AMP-sensitive kinase. Phosphorylation of acetyl-CoA carboxylase results in its inactivation. [Pg.531]

Hardie, D.G., Guy, P.S. 1980. Reversible phosphorylation and inactivation of acetyl-CoA carboxylase from lactating rat mammary gland by cyclic AMP-dependent protein kinase. Eur. J. Biochem. 110, 167—177. [Pg.85]

The ketogenic action of glucagon is probably related in part to cAMP-dependent phosphorylation and inactivation of acetyl-CoA carboxylase [125,126], This would... [Pg.252]

Insulin is an antilipolytic hormone, and its effect on adipose tissue is to increase the transport of glucose into the fat cell, to stimulate lipogenesis and inhibit lipolysis. Thus, pyruvate dehydrogenase and acetyl-CoA carboxylase are activated, and the hormone-sensitive lipase is inactivated. In the normal, well-fed state insulin stimulates the deposition of fat. [Pg.394]

Acetyl CoA Carboxylase Acetyl CoA carboxylase catalyzes the first and rate-Umiting step of fatty acid synthesis carboxylation of acetyl CoA to malonyl CoA. The mammalian enzyme is activated allostericaUy by citrate and isocitrate, and inhibited by long-chain fatty acyl CoA derivatives. It is also activated in response to insulin and inactivated in response to glucagon. [Pg.330]


See other pages where Acetyl-CoA carboxylase inactivation is mentioned: [Pg.124]    [Pg.124]    [Pg.818]    [Pg.78]    [Pg.16]    [Pg.3]    [Pg.138]    [Pg.228]    [Pg.124]    [Pg.915]    [Pg.181]    [Pg.196]    [Pg.432]    [Pg.433]    [Pg.322]    [Pg.326]    [Pg.389]    [Pg.518]    [Pg.525]    [Pg.155]    [Pg.928]   


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Acetyl carboxylase

Acetyl-CoA

Acetyl-CoA acetylation

Acetyl-CoA carboxylases

Carboxylase

Carboxylases

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