Well-fed state

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. 

In the well-fed state, galactose can enter glycolysis or contribute to glycogen storage... 

Regulation of glycogen synthesis and degradation in the well-fed state ... 

In the well-fed state, glycogen synthase is allosterically activated by glucose 6-phosphate when it is present in elevated concentrations (Figure 11.9). In contrast, glycogen phosphorylase is allosterically inhibited by glucose 6-phosphate, as well as by ATP,... 

Increased activity of the hexose monophosphate pathway (HMP) The increased availability of glucose 6-phosphate in the well-fed state, combined with the active use of NADPH in hepatic lipogenesis, stimulate the HMP (see Chapter 12, p. 143). This pathway typically accounts for five to ten percent of the glucose metabolized by the liver (see Figure 24.3, ). 

Decreased triacylglycerol degradation Elevated insulin favors the dephosphorylated (inactive) state of hormone-sensitive lipase (see p. 187). Triacylglycerol degradation is thus inhibited in the well-fed state. 

Fatty acids are released from chylomicrons and VLDL by the action of lipoprotein lipase (see pp. 226, 229). However, fatty acids are of secondary importance as a fuel for muscle in the well-fed state, in which glucose is the primary source of energy. 

In the well-fed state, the brain uses glucose exclusively as a fuel, completely oxidizing approximately 140 g/day to carbon dioxide and water. The brain contains no significant stores of glycogen and is, therefore, completely dependent on the availability of blood glucose (Figure 24.7, O). 

Which one of the following statements concerning the well-fed state is correct ... 

When cells are continually occupied, they reduce the number of receptors to avoid having the metabolic effects overstimulated. For example, two kinds of diabetes exist, Type I and Type II. Type I diabetes, sometimes called juvenile diabetes, results from the inability of the pancreas to supply insulin. Type II diabetes, sometimes called adult-onset diabetes, is more common and correlates with obesity. In this situation, the body senses itself to be in a well-fed state and releases insulin from the pancreas. The large concentration of insulin causes the recipient cells to be fully stimulated. Consequently, they down-regulate their insulin receptor population to bring the response... 

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. 

LPL catalyses the hydrolysis of triacylglycerols to hherate free fatty acids and glycerol. LPL is specifically found in endothelial cells lining the capillaries. LPL has different isoenzyme forms in different tissues that form found in adipocytes is activated hy insuhn (which helps to explain why adipose cells gain fat in a well-fed state). 

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