Glucose (C6H12O6), also known as D-glucose, dextrose, grape sugar, and the more common corn sugar (syrup) or blood sugar, is found in everyday life. One of the first discoveries of glucose came from Andreas Sigismund Marggraf, a German chemist from Berlin and a pioneer of analytical chemistry, who extract sugar (composes of glucose), out of beets using a method with alcohol. Later in 1747, Marggraf isolated and purified the molecule, itself, from raisins using extraction techniques, which the named grape sugar is referred to. He discovered that glucose is less sweet than table sugar because the molecule is a monosaccharide and a carbohydrate that has one of the smallest units of carbohydrate class with molecular weight of 180.15g/mol. This simple sugar is one of the most important sources of energy and functions in organisms, including humans, animals, and plants for their daily lives.
In plants, glucose has multiple functions, specifying, it aids plants to build cell walls and uses as energy sources. Glucose is a component of starch, which starch contains repeated units of the molecule to construct walls of photosynthetic cells. The structure is plant fibers that contains hundreds of thousands of sugar molecules bounded together to provide nutrient not only for plants to grow, yet, also for herbivore consumption. In term of energy sources, two processes, photosynthesis and metabolism are involved for plants to generate and use energy, as the two reactions are interchangeable. In the first process, plants goes through photosynthesis using sunlight to catalyze carbon dioxide and water to make glucose and oxygen (see below).
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When night time arrives, plants use the stored glucose, which is located in sap of plants, and oxygen to make water and carbon dioxide through aerobic respiration. This step is an oxidation reaction that occurs in the plant cells to provide energy for cell to use:C6H12O6 + 6O2 --> 6CO2 + 6H2O.
In living organisms, oxidation of glucose provides energy cells need through series of complex reaction. The first biological process of breaking up glucose is glycolysis, producingpyruvate with a net production of coenzymes including 2 ATPand the reduction of 2 NAD+ to NADH. Pyruvate is the first sequence for other processes in cellular respiration. The entire glycolysis process is energetically downhill and mediated by 10 enzymes. Variable concentrations of AMPand ADP,both are nucleotides, control glycolysis by phosphorylation and dephosphorylation of phosphofructokinase.
(include diagrams of the glycolysis process for reference of the description)
Pyruvate Adenosine Triphosphate (ATP) Adenosine monophosphate (AMP)
Adenosine diphosphate(ADP)Nicotinamide adenine dinucleotide (NAD+)
Another key process that requires glucose is gluconeogenesis, which both animals and humans experience (see figure below). The main site of gluconeogenesis is the liver in animals. Under certain conditions, it occurs in the small intestine and the kidney to a more limited extent. This process forms glucose from fats and proteins, substances other than carbohydrates. Gluconeogenesis is described by the following reaction: 2 pyruvate + 2 NADH + 4 ATP + 2 GTP à Glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi. 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 PhosphoglycerateMutase. 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 TriosephosphateIsomerase. 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. PhosphoglucoseIsomerase 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.
When the concentration of carbohydrate is low because of fasting or starvation, glucose can still be generated. The source of oxaloacetate or pyruvate for gluconeogenesis is obtained from amino acid catabolism. Protein obtained from muscle may have to be broken down to supply the body with amino acids. They are transferred to the liver and delaminated to convert to gluconeogenesis inputs. Fat cells also contribute to gluconeogenesis inputs. They provide triacylglycerol, which is hydrolyzed to glycerol. When the blood glucose level is low, the hormone glucagon triggers liver cells to activatesthe effects of cyclic AMP cascade. Protein Kinase A or cAMP-Dependent Protein Kinase stimulates gluconeogenesis by phosphorylating regulatory proteins and enzymes in the liver.
Triacylglycerol
Glucose is normally found in human bloodstream with a normal concentration of .1%. Any higher concentration will be problematic. To prevent gluconeogenesis process from occurring when glucose is not necessary for the body, 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 (see diagram for general oviewview). 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.
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The Cori Cycle is also operated during cancer, but with increased in operation (see figure below). 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.
Source: Cachexia in cancer patients, Michael J. Tisdale, Nature Reviews Cancer 2, 862-871(November 2002), doi:10.1038/nrc927.
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 2017.
Officially known as diabetes mellitus, this is a disease that 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.
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 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 phosphorylaseB. Therefore, a high glucose concentration stimulates glycogen synthesis by converting phosphorylaseA to phosphorylaseC. 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”.
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 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.
Source: from AP image.
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 to detect people with a higher risk of diabetes.
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 worth waiting product of the future.
Works Cited
Michael McDarby. Online Introduction to the Biology of Animals and Plants.The Basic Needs for Photosynthesis. 2014.
Joyce J. Diwan. Gluconeogenesis; Regulation of Glycolysis and Gluconeogenesis.Molecular Biochemistry I. 2007.
TechCrunch. Google Unveils Smart Contact Lens That Lets Diabetics Measure Their Glucose Levels. 2014.
Google Blog. Introducing Our Smart Contact Lens Project. 2014.
Voet, Donald, Judith G. Voet, and Charlotte W. Pratt.Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2013. Print.