Adipose tissue uses fatty acids and glucose for energy. The liver primarily uses fatty acid oxidation for energy. Muscle cells use fatty acids, glucose, and amino acids as energy sources. Most cells use glucose for ATP synthesis, but there are other fuel molecules equally important for maintaining the body's equilibrium or homeostasis.
Indeed, although the oxidation pathways of fatty acids, amino acids, and glucose begin differently, these mechanisms ultimately converge onto a common pathway, the TCA cycle, occurring within the mitochondria Figure 1. As mentioned earlier, the ATP yield obtained from lipid oxidation is over twice the amount obtained from carbohydrates and amino acids.
So why don't all cells simply use lipids as fuel? In fact, many different cells do oxidize fatty acids for ATP production Figure 2. Skeletal muscle cells also oxidize lipids. Indeed, fatty acids are the main source of energy in skeletal muscle during rest and mild-intensity exercise. As exercise intensity increases, glucose oxidation surpasses fatty acid oxidation. Other secondary factors that influence the substrate of choice for muscle include exercise duration, gender, and training status.
Another tissue that utilizes fatty acids in high amount is adipose tissue. Since adipose tissue is the storehouse of body fat, one might conclude that, during fasting, the source of fatty acids for adipose tissue cells is their own stock. Skeletal muscle and adipose tissue cells also utilize glucose in significant proportions, but only at the absorptive stage - that is, right after a regular meal. Other organs that use primarily fatty acid oxidation are the kidney and the liver.
The cortex cells of the kidneys need a constant supply of energy for continual blood filtration, and so does the liver to accomplish its important biosynthetic functions. Despite their massive use as fuels, fatty acids are oxidized only in the mitochondria. But not all human cells possess mitochondria! Although that may sound strange, human red blood cells are the most common cells lacking mitochondria. Other examples include tissues of the eyes, such as the lens, which is almost totally devoid of mitochondria; and the outer segment of the retina, which contains the photosensitive pigment.
You may have already guessed that these cells and tissues then must produce ATP by metabolizing glucose only. In these situations, glucose is degraded to pyruvate, which is then promptly converted to lactate Figure 2.
This process is called lactic acid fermentation. Although not highly metabolically active, red blood cells are abundant, resulting in the continual uptake of glucose molecules from the bloodstream. Additionally, there are cells that, despite having mitochondria, rely almost exclusively on lactic acid fermentation for ATP production. This is the case for renal medulla cells, whose oxygenated blood supply is not adequate to accomplish oxidative phosphorylation.
Finally, what if the availability of fatty acids to cells changes? The blood-brain barrier provides a good example. In most physiological situations, the blood-brain barrier prevents the access of lipids to the cells of the central nervous system CNS.
Therefore, CNS cells also rely solely on glucose as fuel molecules Figure 2. In prolonged fasting, however, ketone bodies released in the blood by liver cells as part of the continual metabolization of fatty acids are used as fuels for ATP production by CNS cells. In both situations and unlike red blood cells, however, CNS cells are extremely metabolically active and do have mitochondria. Thus, they are able to fully oxidize glucose, generating greater amounts of ATP.
Indeed, the daily consumption of nerve cells is about g of glucose equivalent, which corresponds to an input of about kilocalories 1, kilojoules. However, most remaining cell types in the human body have mitochondria, adequate oxygen supply, and access to all three fuel molecules. Which fuel, then, is preferentially used by each of these cells? Virtually all cells are able to take up and utilize glucose. What regulates the rate of glucose uptake is primarily the concentration of glucose in the blood.
Glucose enters cells via specific transporters GLUTs located in the cell membrane. There are several types of GLUTs, varying in their location tissue specificity and in their affinity for glucose. Adipose and skeletal muscle tissues have GLUT4, a type of GLUT which is present in the plasma membrane only when blood glucose concentration is high e.
The presence of this type of transporter in the membrane increases the rate of glucose uptake by twenty- to thirtyfold in both tissues, increasing the amount of glucose available for oxidation. Therefore, after meals glucose is the primary source of energy for adipose tissue and skeletal muscle.
The breakdown of glucose, in addition to contributing to ATP synthesis, generates compounds that can be used for biosynthetic purposes. So the choice of glucose as the primary oxidized substrate is very important for cells that can grow and divide fast. Examples of these cell types include white blood cells, stem cells , and some epithelial cells. A similar phenomenon occurs in cancer cells, where increased glucose utilization is required as a source of energy and to support the increased rate of cell proliferation.
Interestingly, across a tumor mass, interior cells may experience fluctuations in oxygen tension that in turn limit nutrient oxidation and become an important aspect for tumor survival. In addition, the increased glucose utilization generates high amounts of lactate, which creates an acidic environment and facilitates tumor invasion.
Another factor that dramatically affects the metabolism is the nutritional status of the individual — for instance, during fasting or fed states.
After a carbohydrate-rich meal, blood glucose concentration rises sharply and a massive amount of glucose is taken up by hepatocytes by means of GLUT2. This type of transporter has very low affinity for glucose and is effective only when glucose concentration is high.
Thus, during the fed state the liver responds directly to blood glucose levels by increasing its rate of glucose uptake. In addition to being the main source of energy, glucose is utilized in other pathways, such as glycogen and lipid synthesis by hepatocytes. The whole picture becomes far more complex when we consider how hormones influence our energy metabolism.
Fluctuations in blood levels of glucose trigger secretion of the hormones insulin and glucagon. How do such hormones influence the use of fuel molecules by the various tissues? Demands by one cell type can be met by the consumption of its own reserves and by the uptake of fuel molecules released in the bloodstream by other cells.
Energy use is tightly regulated so that the energy demands of all cells are met simultaneously. Virtually all cells respond to insulin; thus, during the fed state cell metabolism is coordinated by insulin signaling. Figure 3: Blood glucose concentration after carbohydrate-rich and carbohydrate-poor meals. An extraordinary example is how insulin signaling rapidly stimulates glucose uptake in skeletal muscle and adipose tissue and is accomplished by the activity of GLUT4.
In the absence of insulin, these transporters are located inside vesicles and thus do not contribute to glucose uptake in skeletal muscle and adipose tissue. Insulin, however, induces the movement of these transporters to the plasma membrane, increasing glucose uptake and consumption. As different tissues continue to use glucose, the blood glucose concentration tends to reach the pre-meal concentration Figure 3.
Therefore, during fasting, cell metabolism is coordinated by glucagon signaling and the lack of insulin signaling. As a consequence, GLUT4 stays inside vesicles, and glucose uptake by both skeletal muscle cells and adipocytes is reduced. Now, with the low availability of glucose and the signals from glucagon, those cells increase their use of fatty acids as fuel molecules.
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It looks like your browser does not have JavaScript enabled. Please turn on JavaScript and try again. Important Phone Numbers. Topic Contents Topic Overview Credits. Top of the page. Carbohydrates, Proteins, Fats, and Blood Sugar. Topic Overview The body uses three main nutrients to function— carbohydrate , protein , and fat. Nutrients needed by the body and what they are used for Type of nutrient Where it is found How it is used Carbohydrate starches and sugars Breads Grains Fruits Vegetables Milk and yogurt Foods with sugar Broken down into glucose, used to supply energy to cells.
Extra is stored in the liver. Protein Meat Seafood Legumes Nuts and seeds Eggs Milk products Vegetables Broken down into amino acids , used to build muscle and to make other proteins that are essential for the body to function. To learn more about Healthwise, visit Healthwise. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated. Updated visitor guidelines. Top of the page.
Carbohydrates, Proteins, Fats, and Blood Sugar. Topic Overview The body uses three main nutrients to function— carbohydrate , protein , and fat. Nutrients needed by the body and what they are used for Type of nutrient Where it is found How it is used Carbohydrate starches and sugars Breads Grains Fruits Vegetables Milk and yogurt Foods with sugar Broken down into glucose, used to supply energy to cells. Extra is stored in the liver. Protein Meat Seafood Legumes Nuts and seeds Eggs Milk products Vegetables Broken down into amino acids , used to build muscle and to make other proteins that are essential for the body to function.
Fat Oils Butter Egg yolks Animal products Broken down into fatty acids to make cell linings and hormones. When the blood sugar level falls below that range, which may happen between meals, the body has at least three ways of reacting: Cells in the pancreas can release glucagon , a hormone that signals the body to produce glucose from glycogen in the muscles and liver and release it into the blood.
When glycogen is used up, muscle protein is broken down into amino acids. The liver uses amino acids to create glucose through biochemical reactions gluconeogenesis. Fat stores can be used for energy, forming ketones.
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