Control of Carbohydrate Metabolism Hormonal Regulation

Hormones regulate (activate or inhibit) specific enzymes that catalyze the reactions of metabolic pathways. This is achieved mainly by covalent regulation or by conversion of the enzymes into their active or inactive form. Furthermore, hormones can control enzymes by induction or regulation of their transcription. Regulation of the expression of specific genes controls the concentrations of the enzymes and transport proteins necessary for carbohydrate metabolism.

Insulin When a meal is ingested, glucose is liberated as a result of the hydrolysis of dietary carbohydrate in the small intestine, and it is then absorbed into the blood. Increased glucose concentrations stimulate the production and secretion of insulin by the fi cells of the pancreas. Insulin promotes the transfer of glucose into the target cells (i.e., skeletal muscle, liver, and adipose tissue) for use as energy and for storage in the form of glycogen, primarily in the liver.

Insulin also stimulates glycolysis by increasing the activity of glycogen synthase (Figure 3) and the transcription of glycolytic enzymes (Figure 4). Insulin inhibits gluconeogenesis by decreasing the transcription of several gluconeogenic enzymes (Figure 4) and by moderating the peripheral release of gluconeogenic precursors.

Fasting results in a decrease in insulin concentration and a reduction in glucose uptake by the muscle and adipose tissue, which use alternate forms of energy (e.g., free fatty acids). Glucose then becomes available for uptake by the brain, red blood cells, and renal medulla, which are strongly dependent on glucose for energy.

Glucagon Glucagon is a hormone secreted in the bloodstream by the a cells of the pancreas in response to low glucose levels. Glucagon counteracts the action of insulin, and its main role is to stimulate hepatic glucose output and to maintain glucose homeostasis. Glucagon stimulates glycogenolysis by activating glycogen phosphorylase and inhibits gly-cogen synthesis by inactivating glycogen synthase (Figure 3). Furthermore, glucagon stimulates gluco-neogenesis by increasing the gene expression of gluconeogenic enzymes and by blocking glycolysis. In the liver, glucagon enhances the rate of gluco-neogenesis by lipolysis, resulting in increased concentrations of free fatty acids and glycerol.

Catecholamines Epinephrine and norepinephrine are catecholamines that have a regulatory effect on

Alanine

Glucagon

Epinephrine

Fructose 1,6 P2

Insulin

Phospho enolpyruvate

Pyruvate

Insulin

Oxaloacetate

Figure 3 Points of regulation of glycogen synthesis and breakdown.

Glucokinase Hexokinase

Glucose

Glucose 6-phosphatase

Glucose 6-phosphate

Glucose 1-phosphate

Glycogen Phosphorylase ■ Kinase

Glycogen Phosphorylase

Glycogen Synthase

Glycogen

Figure 4 Regulation of glycolysis and gluconeogenesis in the liver.

carbohydrate metabolism. This effect is mainly dependent on the type of receptor present on each cell. Catecholamine receptors are divided into two types: two a receptors and three 0 receptors. The 0 and a-1 receptors stimulate catabolic reactions, while the a-2 receptor inhibits them. The presence of different catecholamine receptors on different cell types explains the selective breakdown of stores from certain tissues.

During fasting, catecholamines stimulate gluco-neogenesis and glycogenolysis in the liver, as a result of increased secretion of glucagon by epinephrine. Catecholamines normally do not play a central role in maintaining glucose homeostasis during fasting, but they prevent hypoglycaemia when glucagon secretion is low.

Glucocorticoids Cortisol, the principal glucocorticoid, stimulates hepatic glucose output and the expression of genes encoding for gluconeogenic enzymes, thus stimulating gluconeogenesis. Cortisol is essential for the action of several hormones and has a much slower effect on hepatic glucose production than either glucagon or the catecholamines, taking several hours to take place.

Growth hormone Growth hormone, like cortisol, increases hepatic glucose production by changing substrate availability and promoting the expression of gluconeogenic enzymes. Growth hormone secretion is enhanced by starvation. Like cortisol, growth hormone affects hepatic glucose production much more slowly than glucagon or the catecholamines, taking several hours to occur.

Allosteric Enzyme Regulation

Allosteric enzymes are activated or inhibited by substances produced in the pathway in which the enzymes function. These substances are called modulators and can alter the activity of allosteric enzymes by changing their conformation. Adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) are important modulators of allosteric enzymes in carbohydrate metabolism. The effects of ATP are opposed by those of AMP and ADP. When energy supply is adequate, ATP accumulates and negatively modulates enzymes that catalyze energy-producing or catabolic pathways, e.g., glycolysis. When energy is depleted and ATP concentration is decreased, AMP and ADP accumulate. As a result, allosteric enzymes in catabolic pathways are positively modulated and energy is produced. An increase in ATP inhibits further energy production and blocks glycolytic enzymes, while an increase in AMP or ADP stimulates glycolytic enzymes for energy production (Figure 3).

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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