The body has different ways in which it can regulate energy metabolism; that is, decide whether to increase energy or reduce energy production. Two main ways are highlighted in this lesson with examples, i.e., allosteric inhibition/activation, and hormones.
Allosteric Inhibition and Activation
Remember that allosteric regulation happens when a substance binds to a site on the enzyme that is not the active site. This site is known as the allosteric site. This action either causes inhibition or greater activity of the enzyme.
Regulation of Glycolysis
Example 1: When energy level is high, glucose-6-phosphate is also high. Therefore to reduce energy production, glucose-6-phosphate binds and inhibits hexokinase, reducing the conversion of glucose to glucose-6-phosphate.
Example 2: When energy level is high, citrate and ATP are also high. Therefore to reduce energy production, citrate and ATP binds and inhibits phosphofructokinase, reducing the conversion of fructose-6-phosphate to fructose 1, 6 phosphate. When energy is low, AMP is high. Therefore to increase energy production, AMP binds and promotes phosphofructokinase, increasing the conversion of fructose-6-phosphate to fructose 1, 6 phosphate. Fructose 2, 6 biphosphate also plays a critical role in promoting glycolysis by allosterically binding to phosphofructokinase.
Example 3: When energy is high, acetyl CoA, ATP, and alanine are high. Therefore to reduce energy production, acetyl CoA, ATP, and alanine binds and inhibits pyruvate kinase, reducing the conversion of phosphoenolpyruvate to pyruvate. When energy is low, fructose 1, 6 biphosphate is high. Therefore to increase energy production, fructose 1, 6 biphosphate promotes pyruvate kinase, increasing the conversion of phosphoenolpyruvate to pyruvate.
Regulation of Pyruvate to Acetyl CoA
When energy is high, acetyl CoA, ATP, and NADH are high. Therefore to reduce energy production, acetyl CoA, ATP, and NADH binds and inhibits pyruvate dehydrogenase, reducing the conversion of pyruvate to acetyl CoA. When energy is low, CoA, NAD+, AMP, and phosphoenolpyruvate are high. Therefore to increase energy production, CoA, NAD+, AMP, and phosphoenolpyruvate promote pyruvate dehydrogenase, increasing the conversion of pyruvate to acetyl CoA.
Regulation of Gluconeogenesis
When energy is high, acetyl CoA is also high. Therefore acetyl CoA binds to fructose 1, 6 biphosphatase, promoting the conversion of 1,6 biphosphate to fructose 6 phosphate and ultimately enabling more glucose to be made. When energy is low, AMP is also low. Therefore AMP binds to fructose 1, 6 biphosphatase, inhibiting the conversion of 1,6 biphosphate to fructose 6 phosphate. Ultimately, more glucose is burned for energy rather than being made. Fructose 2, 6 biphosphate also inhibits glucose production via allosteric inhibition of fructose 1, 6 biphosphatase when energy is low.
Regulation of Glycogen Synthesis
Regulation of glycogen synthesis is done by controlling the activity of glycogen synthase, the key enzyme responsible for making glycogen. Dephosphorylation of glycogen synthase by phosphatases, allosterically promotes glycogen synthase, making more glycogen. Phosphorylation of glycogen synthase by kinases allosterically inhibits glycogen synthase, making less glycogen.
Regulation of Glycogenolysis
As in glycogenesis, regulation of glycogen breakdown is controlled by phosphorylation and dephosphorylation activities. Kinases promote glycogen phosphorylase, increasing glycogen breakdown, while phosphorylases inhibit glycogen phosphorylase, decreasing glycogen breakdown. ATP and AMP also play a critical role by allosterically inhibiting and enhancing glycogen degradation respectively. When energy level is high (high ATP), there is no need to pull on glycogen reserves. However, when energy level is low (high AMP), glycogen resources must be tapped into.
Regulation by Hormones
Insulin and Glucagon
Insulin and glucagon are hormones produced by the pancreas in a tissue called the islets of Langerhans. They are both responsible for controlling the amount of glucose in the blood. Insulin is made in cells in this area known as beta cells, while glucagon is made in alpha cells. Insulin promotes glucose uptake from the blood, and energy storage via glycogenesis and lipogenesis. Glucagon promotes glucose production via glycogenolysis and gluconeogenesis, and the release of glucose into the blood.
Insulin binds to insulin receptor proteins on the cell membrane (liver, muscle, and adipose cells), which activates a signal transduction cascade. This ultimately opens glucose transport proteins in the cell membrane, allowing glucose to enter.
Glucagon binds to G-protein coupled receptors on cell membranes in the liver, producing a signal transduction cascade that ultimately promotes glycogen phosphorylase, and hence glycogenolysis. In the signal transduction cascade, GDP that is bound to G-protein is replaced with GTP. This causes G-protein to be released from the G-protein-coupled receptor and bind to adenylate cyclase in the membrane. This enzyme causes ATP to be converted to cAMP. cAMP activates protein kinase A, which activates phosphorylase kinase, which activates glycogen phosphorylase.
