The body has different ways in which it can regulate energy metabolism; that is, decide whether to increase energy or reduce energy production. Three ways are highlighted in this lesson.
Allosteric Inhibition and Activation
When there is lots of ATP, cells do not have to work so hard to make more. Therefore, it uses a type of feedback mechanism known as allosteric inhibition to slow down certain enzymes and hence the products that they make. Allosteric inhibition simply means that a molecule attaches to the non-catalytic site of the enzyme, changing their shape and hence preventing them from working. Examples of this type of inhibition is seen in the inhibition of pyruvate kinase and phosphofructokinase (PFK) by ATP.
High levels of citrate can also inhibit PFK, slowing down the TCA cycle. When ATP supply is low, its production must be ramped up. This is done by AMP allosterically binding to PFK, increasing its activity and hence moving glycolysis along.
Another example of allosteric inhibition is the control of pyruvate dehydrogenase by ATP and NADH. Pyruvate dehydrogenase is responsible for converting pyruvate to acetyl-CoA. When there is high ATP and NADH, this means that energy is well supplied and therefore less acetyl-CoA is needed to fuel the TCA cycle. However, when more energy is needed, ADP allosterically binds to pyruvate dehydrogenase to activate it.
Pyruvate dehydrogenase is also regulated by its substrate and product. That is, if there is lots more pyruvate (substrate) than acetyl CoA (product), the enzyme will work harder but if there is lots more acetyl CoA than pyruvate, it will slow down. In addition to their allosteric control of pyruvate dehydrogenase, ATP and NADH also inhibits isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase in the TCA cycle. ADP acts in the opposite direction by increasing their activity.
Insulin and Glucagon Hormones
Insulin and glucagon are hormones produced by the pancreas that are responsible for controlling the amount of glucose in the blood. Insulin is made in the beta cells of the pancreas. It is released after a meal when glucose in the blood is high. It binds to insulin receptors on the surface of cells which in turn opens glucose channels for glucose to enter the cells. With access to glucose, cells can then actively break it down to produce energy through glycolysis. When glucose levels are low such as when you are hungry, glucagon is released from the alpha cells of the pancreas into the blood. In the liver, glucagon binds to glucagon receptors stimulating the liver to breakdown glycogen to glucose (glycogenolysis). Glucagon also promotes production of glucose from non-carbohydrate substrates (gluconeogenesis), reduce fatty acid storage and increase lipolysis so that more lipids is available for energy production.
Has anyone ever told you that you have a high metabolic rate? This refers to how fast you normally burn energy. The amount of energy that we burn when we are at rest is called basal metabolic rate (BMR). It is the thyroid gland that regulates your BMR. The thyroid gland is a butterfly-shaped gland sitting on the front of the neck. It takes up iodide (I-) which we absorb into our blood from food, and use it to make thyroid hormones Triiodothyronine (T3), and Thyroxine (T4). When your energy levels are low, the thyroid gland is stimulated by thyroid-stimulating hormones (TSH) from the pituitary gland to make T3 and T4. T3 and T4 are transported to your cells via thyroid protein transporters in the blood. Once in the cell, thyroid hormones activate genes responsible for protein transcription of enzymes needed to run the mitochondria.
Reference: Thompson,& J., Manore, M., Vaughan, L. (2020). The science of nutrition (5th ed.). New York. Pearson