Brandon Kurniawan Jessica Ly Milton Ma. Glucose

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1 Brandon Kurniawan Jessica Ly Milton Ma Glucose One of the main essential organic molecules that human body requires is glucose (C 6 H 12 O 6 ), also known as D-glucose, dextrose, and grape sugar. Andreas Sigismund Marggraf, a German chemist from Berlin and a pioneer of analytical chemistry, was the first to extract glucose out of beets using a method with alcohol. It was later purified by his student, Franz Achard. This discovery lead the way to improved advancements in the field of organic chemistry because of this molecule s importance in many organisms. With a molar mass of 180 g/mole, due to the more massive oxygen, its density is 1.54 g/cm 3, and can be found in the form of a white powder. Glucose is also colorless and is very soluble in water as well as acetic acid and several other solvents and can be crystallized from these solvents into three major forms: alpha-glucopyranose, beta-glucopyranose, and betaglucopyranose hydrate. Glucose is essential in many life processes, in the human body, and in other living creatures. These include plants, diabetes, glycogen, gluconeogenesis, glycolysis, alpha-beta adrenergic receptors, metabolism, glucose uptake in the liver and muscle, and in certain diseases. In plants, glucose is stored as starch, which are repeating units of sugar. Plants produce sugar by converting carbon dioxide and water in the presence of light. This process is important in all photosynthetic organisms so that they may produce this essential molecule to be consumed in our diet. Starch is the major structural component in cell walls of photosynthetic cells. Plant fibers are shown to be highly nutritious once broken down into hundreds of thousands of sugar molecules that are bounded together. Not only animals, but plants also use glucose as an energy source. When light is unavailable, plants undergo dark reactions for their sugar processing. Photosynthetic organisms still require energy when they cannot perform photosynthesis. These organisms acquire energy in the form of adenosine triphosphate (ATP) through aerobic respiration using oxygen and glucose and breaking it down to water and carbon dioxide. Glycolysis is a heavily regulated enzymatic process in both animals and plants that breaks down glucose into small intermediates and ultimately into pyruvate. The breakdown of glucose into pyruvate results in a net production of 2 ATP and the reduction of 2 NAD+ to NADH. The entire process is energetically downhill and mediated by 10 enzymes. Despite the small amount of ATP generated, the high-energy intermediates (NADH and FADH) formed from glycolysis are moved to the cell s mitochondria where it is utilized in the oxidative phosphorylation. Variable concentrations of AMP and ADP control glycolysis by phosphorylation and dephosphorylation of the enzyme, phosphofructokinase. Another key process that requires glucose is gluconeogenesis. The main site of gluconeogenesis is in the liver of animals. Under certain conditions, it occurs in the small

2 intestine and the kidney to a more limited extent. This process forms substances other than carbohydrates, such as glucose from fats and proteins. Gluconeogenesis is described by the following reaction: 2 pyruvate + 2 NADH + 4 ATP + 2 GTP + Glucose + 2 NAD ADP + 2 GDP + 6 P i. Pyruvate carboxylase expends ATP and bicarbonate to convert pyruvate into oxaloacetate. GTP s high energy phosphate bond is broken by PEP carboxykinase to produce phosphoenolpyruvate. It then turns into 2-phosphoglycerate with the release of water from Enolase. 2-phosphoglycerate turns into 3-phosphoglycerate by Phosphoglycerate mutase. Phosphoglycerate kinase uses ATP to convert 3-phosphoglycerate into 1,3-Bisphosphoglycerate. It then becomes glyceraldehyde 3-phosphate from Glyceraldehyde-3-phosphate Dehydrogenase with the help of NADH. Glyceraldehyde-3-phosphate can be interchanged with dihydroxyacetone-phosphate by Triosephosphate isomerase. Aldolase converts glyceraldehyde- 3-phosphate and dihydroxyacetone-phosphate into fructose-1,6-bisphosphate. This molecule is then converted into fructose-6-phosphate with the addition of water by fructose-1,6- bisphosphatase. Phosphoglucose isomerase transforms fructose-6-phosphate into glucose-6- phosphate and then it finally becomes glucose with the addition of water from Glucose-6- phosphatase. This pathway is spontaneous, but overall, it consumes six phosphate bonds of GTP and ATP. During the fasting or starvation of carbohydrates, glucose can still be obtained. The source of oxaloacetate or pyruvate for gluconeogenesis is obtained from amino acid catabolism. Protein obtained from muscle will be broken down to supply the body with essential amino acids. Amino acids are transferred to the liver and then deaminated to convert to gluconeogenesis inputs. Fat cells also contribute to gluconeogenesis inputs. They provide triacylglycerol, which is hydrolyzed to form the glycerol backbone. When the blood glucose level is low, the hormone glucagon triggers liver cells to activate the effects of the cyclic AMP cascade. Protein Kinase A or camp-dependent Protein Kinase stimulates gluconeogenesis by phosphorylating regulatory proteins and enzymes in the liver.

3 To prevent the unnecessary production of glucose, fructose-1,6-bisphosphatase is inhibited by AMP. When there is a high concentration of AMP and a low concentration of ATP, glucose will not be synthesized because the cell would have to expend energy. During exercise, when ATP is needed, the Cori Cycle occurs. In a short span of time, a lot of ATP is required to produce energy for exercising. The high energy phosphate bond is taken from phosphocreatine and used by muscle cells. When the supply of phosphocreatine is out, ATP is taken from glycolysis, obtaining it from the glucose uptake from the body s blood or from glycogen breakdown. The Cori Cycle also operates in the cancer cells of an inflicted organism. This cycle is activated when the body s metabolism is changed to anaerobic metabolism due to the underdevelopment of blood vessels compared to the growth of a tumor. The tumor causes a decrease in the oxygen concentration. Because of the tumor, this cycle spends six phosphate bonds from the liver in order to produce two phosphate bonds from glycolysis, resulting in more energy spent than it is gained. Even with a regular intake of food/glucose, the body is still losing weight in late-stage cancer. Another disease that glucose largely impacts is diabetes. Diabetes affects nearly 25.8 million children and adults in the United States. If left untreated, it can result in blindness, multiple cardiovascular diseases, high blood pressure, and in serious cases, amputation of limbs. People with this deadly disease must perform regular checks on their glucose level in their blood. The most inexpensive and widely used way of monitoring glucose level is to poke their fingers to draw the blood needed for the test. A 2011 report projected that the global blood glucose test strips and meters market will reach US$21.5 billion by Officially known as diabetes mellitus, this disease/deficiency is caused by a decreased response to insulin in its target tissues or a deficiency of insulin. Diabetes mellitus is one of the best-known endocrine disorders, which is marked by elevated levels of blood glucose. There are two types of diabetes, type 1 diabetes mellitus and type 2 diabetes mellitus. Type 1 diabetes mellitus is insulin-dependent. This is an autoimmune disorder that occurs when the immune system destroys the beta cells in the pancreas. Type 2 diabetes mellitus is more common. This type is non-insulin-dependent. This occurs when there is a deficiency in insulin or there is a reduced response to the target cells because the insulin receptors have been changed or modified, which will not recognize insulin at its receptors. With glucose being so closely linked to diabetes, researchers around the world have been tirelessly looking for ways to cure this disease. While no known cure was discovered, a great deal of progress has been made on the tracking of glucose levels. Recently Google has teamed up with researchers at the University of Washington to develop a contact lens that can measure the blood glucose levels in a person s tears and display the reading on their mobile phone. If this forward-thinking contact lens project is successful, people with or without the disease may be able to stop drawing blood to measure their sugar levels. According to Google, the glucose-sensing contact lens will function similarly to an electronic ID card used to gain access to a building. Like the card, the lens doesn t contain its own power supply. Instead, the antenna integrated in the contact lens will pick up the radio waves from a mobile to provide it with a sustainable power to measure the glucose level. This is one of the first steps in a new and innovative way towards measuring a person s glucose level, a step closer against fighting diabetes.

4 The technology in Google s glucose lenses goes well beyond electronics it contains enzymes and electrodes built into the materials used to make regular contact lenses. This combines advances made in biochemistry, electronics and material sciences during the past decades. So far the problem of this technological advancement is whether or not the sensor can pick up an accurate reading of the glucose level. While the success of this new glucometer isn t guaranteed, this vast improvement in the control of blood glucose would provide health benefits to diabetes patients. Also the potential expansion on other biological information that the sensor may be able to obtain makes this glucose contact lens a promising and worthwhile product of the future. As an energy storage, glucose is stored in the body in the form of glycogen and broken down when the body needs it. When glucose levels are low in the blood, the pancreas responds

5 by producing the hormone, glucagon from alpha cells. Glucagon acts as a ligand and binds to the glucagon receptors on liver cells. Cyclic adenosine monophosphate acts as a messenger to promote glycogen degradation into glucose, which brings the blood glucose level back to homeostasis. When glucose levels are high in the blood, the pancreas responds by producing the hormone, insulin produced by beta cells of the pancreas. Insulin acts as a ligand and binds to the insulin receptors located on both muscle and liver cells. As glucose molecules enter both liver and muscle cells via glucose transporter proteins, glucose is taken up as glycogen. Glycogen degradation is also promoted when the hormone, epinephrine, binds to alpha-adrenergic receptors on liver cells, which leads to increased cytosolic calcium ions. These events also bring the body back to homeostasis. Insulin from the liver directly stimulates glycogen synthesis by inhibiting the glycogen synthase kinase 3-beta, which increases the activity of glycogen synthase by decreasing phosphorylation. Glucose itself inhibits phosphorylase a through binding of the enzyme in its inactive T state and producing a conformational changes, shifting from the R to T state. As a result, this shift exposes the serine amino acid s phosphate group, which will now be open to dephosphorylation. The new enzyme is then called phosphorylase b. Therefore, a high glucose concentration stimulates glycogen synthesis by converting phosphorylase a to phosphorylase b. glycogen synthase is activated by the release of phosphoprotein phosphatase-1. The liver will store excess glucose in the form of glycogen. Too much glycogen uptake by the liver will result in a fatty liver. As a relatively small molecule, glucose sure has huge effects on the human body. While being regulated properly with the cooperation of other molecules, glucose is the key genesis materials of our body s essential energy. However, when being mistreated, glucose and its derivatives can lead to serious health issues like diabetes. As an effect of these mis-regulations, for decades, scientist and engineers have developed ways of regulating and monitoring of blood glucose level. It is hopeful that, in the future, these preventative methods will lead to the ultimate eradication of glucose-related diseases.

6 Works Cited Michael McDarby. Online Introduction to the Biology of Animals and Plants. The Basic Needs for Photosynthesis Photosynthesis.htm Joyce J. Diwan. Gluconeogenesis; Regulation of Glycolysis and Gluconeogenesis. Molecular Biochemistry I TechCrunch. Google Unveils Smart Contact Lens That Lets Diabetics Measure Their Glucose Levels Google Blog. Introducing Our Smart Contact Lens Project Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, Print.