LESSON 2.3 WORKBOOK Part one: Glucose homeostasis in the blood storing energy Glucose metabolism takes place in all cells to make ATP. The liver plays an important role in regulating the levels of glucose in the blood so that the brain has enough glucose to metabolize. In the next two lessons we will focus on the question: How does the liver regulate levels of glucose in the blood? In this lesson we focus on the metabolic pathways the liver uses to shuttle the energy from nutrients into storage as glycogen, fat, and protein. Extra glucose in the blood In the previous lesson we learned about the importance of glucose for cells in the body, and that a constant supply of glucose is needed in order for cells to make ATP for survival. Glucose can be transported in the blood, but ATP can t, so each cell in your body is relying on a steady supply of glucose in order to build ATP. If blood glucose levels get either too high or too low, the cells cannot function properly. Because of this, our organs have developed a system for maintaining steady blood glucose levels, called glucose homeostasis. Why is glucose homeostasis important? What would happen if blood glucose levels were not maintained? The goal of glucose homeostasis is to deliver glucose to the cells so they can function. The brain uses 60% of the glucose that we take in through our diets. The majority of the remainder is used to maintain body temperature, move blood, contract muscles and maintain cells and tissues. Given that most cells and tissues utilize more nutrients than they can store between meals, there needs to be a source of nutrient delivery to the cells. The blood stream is the buffet table that maintains a constant supply of nutrients for cells. Without this steady supply of nutrients cells cannot function, and if left without nutrients for too long the cells will die. 1. The purpose of glucose homeostasis is: To ensure glucose concentrations do not get dangerously high. To ensure glucose concentrations do not get dangerously low. c. To give tissues a constant supply of glucose. d. All of the above. 82
DEFINITIONS OF TERMS Glycemic index (GI) A system of ranking foods based on their effect on blood glucose concentrations. For a complete list of defined terms, see the Glossary. In some cases, like in diabetes, blood glucose concentrations will get too low or too high for a long period of time. A sudden, sharp drop in blood glucose concentrations can even result in loss of consciousness or coma because the brain is deprived of the energy it needs from glucose. To the contrary, high blood glucose can cause damage to nerves and impairs the body s ability to heal wounds, which can lead to ulcers or in some cases amputation. What causes blood glucose to rise and fall? If all of our organs are functioning properly, the amount of glucose that is entering the blood stream depends entirely on what and when your last meal was. As we saw in Lesson 2.1, simple sugars are easily digested and absorbed in our intestines because they are already in the monomer form; simple sugars get into our blood stream quicker than complex carbohydrates like starches that need rise to a spike in blood glucose levels. If you eat a food that contains both simple sugars along with complex carbohydrates, proteins or lipids, the simple sugars will get tangled up with the harder-to-digest parts of the food, and the amount of glucose in your blood won t spike quite as much. Foods that cause a rapid spike in blood glucose, Figure 2: Soda has a high glycemic index (GI). BLOOD GLUCOSE LEVELS GI High GI Low 1 2 TIME / HOURS Figure 1: Foods with a lot of simple sugars have a high glycemic index (GI) because they cause spikes in blood glucose. Foods with fiber, protein and lipids have a low GI. followed by a sharp drop in blood glucose are said to have a high glycemic index (GI). Contrarily, foods that cause a slow, steady rise in blood glucose after they are eaten have a low glycemic index. You can see both patterns of blood glucose levels in the figure to the right. Sharp spikes in blood glucose will be sensed by the pancreas, which will respond by sending signals to quickly clear the blood of the extra glucose. Quick spikes and drops in your blood glucose will make you feel hungrier than a steady rise and decline in blood glucose. This is why you will still feel hungry after you drink a can of soda, but you would feel full if you ate the same amount of calories from a piece of fruit that contains fiber. 2. Which of the following would cause a rapid spike in blood glucose after eating it? An apple. A turkey sandwich. c. A diet sod d. A glass of orange juice. 83
DEFINITIONS OF TERMS Adipose A type of cell or tissue that is used by the body for the storage of fat. For a complete list of defined terms, see the Glossary. Diabetes is characterized by high blood glucose concentrations Normally, when blood glucose levels are high the body reacts by storing the glucose to use later. If blood glucose levels are left high for too long it can actually cause damage to cells and tissues because the glucose will stick to proteins, changing their function. In diabetes, the normal signals that tell the body to store glucose for later use malfunction, resulting in high blood glucose levels. One of the tests that doctors will conduct to determine if a person has diabetes is testing the amount of glucose in the urine. Normally, glucose is used or stored up by the body and does not get into the urine, but in a diabetic person the extra blood glucose is secreted in the urine. We will learn more about the causes and consequences of diabetes in Unit 3. Storing extra glucose After you eat, nutrients are absorbed and are transported by the blood. Cells will pull the amount of glucose they need out of the blood, and the extra glucose will be stored for later use. This prevents blood glucose levels from remaining high for too long, which in turn prevents the impairment of cellular functions. For the remainder of this lesson we will explore the steps of energy storage in the each of the key organs. In general, the body stores most of its energy in a calorie dense form fat! The pancreas and liver work together to keep blood glucose concentrations constant The pancreas and the liver are two important organs in glucose homeostasis. If we go back to our idea of the blood being a buffet table of nutrients, the pancreas is the wait staff constantly checking the table to make sure that there is the right amount of food on the table at all times, and the liver is the head chef that is busy making the food High%Blood%Glucose% Promotes%Insulin%Release% Pancreas( Insulin% Insulin%Signals%the%Liver% %to%store%glucose%% Liver( Figure 4: High levels of glucose stimulate the pancreas to make insulin that signals the liver to store glucose. Figure 3: High levels of glucose in the urine may indicate diabetes. and sending it out. If there is more glucose in the blood than what is needed by the cells, the pancreas will sense this and send a message in the form of insulin, telling the liver to package the glucose for storage. These messages also go to the storage facilities: adipose (fat) cells store triglycerides and muscle tissue stores glycogen. 3. Which of the following is NOT normally a way that extra glucose in the blood is used? It is excreted in the urine. It is stored as triglycerides. c. It is stored as glycogen. d. It is turned into amino acids. 4. How do tissues know that it is time to store glucose, instead of use glucose? Each tissue can sense blood glucose concentrations. The brain sends messages to the tissues. c. Insulin released from the pancreas sends messages to the tisues. d. The liver sends messages to tissues. 84
DEFINITIONS OF TERMS Lipogenesis The metabolic formation of fat. For a complete list of defined terms, see the Glossary. Glycogen Glycogen Quick limited storage: Glycogen The first storage tanks that get filled up are the glycogen stores. As you recall from Unit 1, glycogen is a long, heavily branched chain of glucose monomers. Glycogen is only stored in the muscles and the liver, and the amount of storage is limited, so every time you eat you probably fill up your glycogen stores. We typically only have room to store up to 18 hours' worth of glucose as glycogen, and these stores are depleted quicker if you exercise. Because glycogen has so many branches, it can be broken down easily, resulting in the quick release of glucose. The glycogen stored in the muscles is the quick source of energy when you are exercising, and the glycogen stored in the liver ensures that glucose can be released into the blood when needed for the brain (the liver is the only organ that can release glucose, so glycogen in the muscle can only provide glucose to that muscle). When blood glucose levels are high, insulin is released from the pancreas which sends a message to the liver and the muscle to store glucose as glycogen. Long term unlimited storage: Fat Glucose Figure 5: The liver and muscles can store extra glucose as glycogen, which provides a quick source of glucose when needed. Acetyl CoA is the important intermediate in the conversion of extra glucose to fat. Remember that during glycolysis glucose is broken down into two molecules of acetyl CoA. When the body has enough ATP, it no longer needs to feed the acetyl CoA into the citric acid cycle. Instead, the acetyl CoA is used to build the fatty acid tails of triglycerides, which are then stored in adipose tissue until needed. The process of making lipids is called lipogenesis. Lipogenesis occurs in the liver, and the triglycerides are then packaged up into the cholesterol lipoprotein called LDL to be sent to other tissues for use or storage. Remember that fatty acids Glucose Acetyl CoA Citric acid cycle Fat (Triglyceride) Lipogenesis Adipose stores fat Figure 6: If you have too much glucose you may store the energy as fat in a process called lipogenesis. Only the liver can make fat from glucose, and it is stored in adipose tissue. 85
Fa#y Acids Nucleus The soda to fat expressway Fructose is the simple sugar that is in fruits, honey and high fructose corn syrup. Naturally occurring fructose in fruits is usually bound up with the fiber of the fruit, making the absorption slow. In food products with corn syrup and high fructose corn syrup, the fructose is free to be easily absorbed. In fact, fructose is more easily absorbed than glucose and once absorbed, fructose is normally converted into glucose in the liver. However, when eaten in high amounts the fructose may be more readily converted into triglycerides than glucose. This is because the use and packaging of fructose is not as highly regulated as glucose, so it is more likely that you have an overload of fructose in the liver than glucose. We tend to eat more fructose in our diets now than ever before, and some scientists think that this increase in fructose consumption is a contributing factor in the rise of obesity rates. Making amino acids Cytoplasm Figure 7: Adipose cells can store a practically unlimited amount of fatty acids. are simply long, straight chains of carbons, so they are easily packed together tightly. Also, because of the large number of carbon bonds, fatty acids are a densely packed source of combustible energy. The triglycerides are bundled up and stored in adipose tissue, or fat tissue. Men tend to store this fat in their bellies, whereas women are more likely to store fat in their hips and thighs, although every person is unique. Our fat stores can expand to make room for new triglycerides, meaning that we have essentially an unlimited capacity to store fat, whether we like it or not! Figure 8: High fructose corn syrup is rapidly absorbed by the body. Although glucose isn t converted into amino acids as a way to store it as energy, several amino acids can be made from glucose. Recall from Unit 1 that there are two types of amino acids in our body: essential and non-essential. Essential amino acids are those that we must eat in our diet because the cells in our body cannot make enough of them. In contrast, non-essential amino acids require proper nutritional intake of the starting components for amino acid synthesis. In fact, eating enough essential amino acids is necessary for the synthesis of some of the non-essential amino acids. 5. All amino acids are made from glucose in the liver. True. False. 86
Cells in the liver make non-essential amino acids from intermediates of glycolysis and the citric acid cycle. When glucose is converted to acetyl CoA in glycolysis it goes through several steps of intermediate molecules. Similarly, in the citric acid cycle there are many intermediate molecules that transfer the carbons from one another. In times when a lot of glucose is available, such as after a meal, liver cells can use the intermediates of glycolysis and the citric acid cycle to make amino acids instead of ATP. This is important because proteins have many key functions in the body: Produce vital body structures: Proteins are the structural support of cells and tissues. Acid/base balance: Amino acids can be acidic or basic and act as a buffer to keep the body ph within a narrow range. Forming hormones, enzymes and neurotransmitters: Amino acids are required to synthesize most of the hormones in the body. Immune function: Antibody proteins are a key component of immune function. Without sufficient dietary protein, the immune system cannot build its antibody defense. Transporting nutrients: Many proteins carry nutrients through the bloodstream to cells and across cell membranes to sites of action (like the proteins working with fats in HDL and LDL). A quick review of today s material The figure to the right orients us to where all of the processes we ve discussed today are occurring. After eating a meal, nutrients are digested and absorbed from the gastrointestinal tract into the blood. The pancreas senses an increase in blood glucose concentrations and secretes insulin. The insulin sends signals to other tissues in the body: in the liver, insulin promotes the repackaging of nutrients for storage; in the muscles insulin stimulates the absorption and storage of glucose as glycogen; in the adipose tissue insulin facilitates the storage of fatty acids as triglycerides. As always, the brain will use the new glucose entering the blood for energy and the kidneys will filter waste from the blood to be excreted as urine. Non- essen0al Amino acids Glucose Acetyl CoA Citric acid cycle Figure 9: The liver can make the non-essential amino acids from intermediates in glycolysis and the citric acid cycle. These amino acids are then delivered to other cells through the blood. Figure 10: Each of the organ s roles during feasting in maintaining glucose homeostasis. 87
STUDENT RESPONSES In diabetes, the messages from the pancreas do not get sent out correctly because insulin does not function. What happens in the liver, adipose and muscle of someone that is diabetic after they eat a meal? Remember to identify your sources 88
TERMS TERM Adipose Glycemic Index Lipogenesis DEFINITION A type of cell or tissue that is used by the body for the storage of fat. A system of ranking foods based on their effect on blood glucose concentrations. The metabolic formation of fat. For a complete list of defined terms, see the Glossary. 89