Warburg Effect

Metabolism refers to the sum of all the necessary chemical processes that allow living organisms to interconvert and use energy to maintain cellular activity. It can be subdivided into two categories, the first process is called catabolism which is the process of breaking down molecules to obtain energy, and the second process is called anabolism which is using energy to synthesize molecules to sustain cellular activity (Mandal et. al, 2013). With the knowledge that all living organisms undergo metabolic processes in order to survive, it is important that we understand the process of metabolism and how specific changes in environmental conditions can affect overall metabolic activity.

Cellular Respiration is one of the most important biochemical reactions. Through a serious of reactions, it is how we get energy from the foods we eat. First in this reaction pathway is glycolysis, or the oxidation of glucose, which occurs in the cytosol in both prokaryotes and eukaryotes. Glucose, a monosaccharide derived from the food we eat, is oxidized into 2 intermediate molecules named pyruvate and energy is released. This process is powered by 2 ATP molecules. ATP can be thought as the “energy currency” of a cell. In addition, the oxidation of glucose powers the phosphorylation of 4 ADP molecules into 4 ATP molecules (producing 2 net ATP in the process), and reduces 2 molecules of the electron carrier NAD+ into 2 NADH

The process of cellular oxidation is essentially an energy transformation process; i which the energy stored in the food molecules am transformed into chemical energy of A (Adenosine triphosphate). Molecular oxygen is taken into the cell, the food molecules are, oxidized and energy, carbon dioxide and water are released.The energy that is released durin the oxidation of the food is used to couple phosphoric acid and ADP (Adenosine diphosphate) to the energy rich ATP. All the three types of food, such as carbohydrates, proteins and lipids are oxidized inside the cell in essentially the same manner. The pathways of these three types of molecules converge on a point known as Krebs cycle.The carbon dioxide produced inside cells diffuses out into blood and finally eliminated through the respiratory system. From the foregoing discussion, it is clear that ATP is the energy currency of the cell. However, it should be noted that ATP does not store energy, but rather transfers it to points in a cell requiring it.It refers to the anaerobic (without oxygen) breakdown of monosaccharides, especially glucose to two molecules of pyruvic acid (pyruvate) with a concominant release of a relatively small amount of energy in the form of ATP. The complete glycolytic pathway was worked out by Gustav Embden, Otto Meyerhoff, Carl Nituberg and Jacob Parnas in 1940.The glycolytic pathway is also known as Embden-Meyerhoff-Parnas (EMP) pathway in the honour of its discoverers. In this pathway, glucose

While Season felt completely broken-down, she knew that she had no choice but to bring her background in nutrition to her own home. To build Kicker’s immunity Season implemented The Ketogenic Diet. The human body produces cancerous cells daily, so building a strong immunity is imperative when fighting off cancer cells and the harsh chemicals from treatment. The Ketogenic Diet is a new cancer treatment, which is free, with virtually no side effects. It can also be conjoined with other cancer treatments. The diet involves cutting carbohydrates, beginning with the worst carbohydrate of all, sugar (Johnson L, 2013). It is a high-fat, adequate-protein, low-carbohydrate diet. The diet forces the body to burn fats rather than carbohydrates. Normally the carbohydrates contained in food are converted into glucose, which are then transported around the body. However, if there are little carbohydrates in the diet then the liver converts fat into fatty acids and ketone bodies. Ketone bodies are water molecules that are produced when the body is consuming very little food, which mimics fasting. Cancer is an obligate glucose metabolizer because it fuels on sugar. One’s normal cells have the metabolic flexibility to adapt from saving glucose by using ketone bodies (Johnson S, 2014). This addressed that because cancer

Background Research: Cellular Respiration is used by the cells to make ATP, by releasing chemical energy from sugars and other carbon based molecules. There are 3 stages to Cellular Respiration, Glycolysis, Krebs Cycle, and the Electron Transport Chain. The inputs of Glycolysis are 2 ATP’s, a Glucose molecule, and a Pyruvate. The inputs for the Krebs Cycle are oxygen, and. In animals, energy is consumed by eating food. In that food they eat, Glucose is found and broken down by the process of cellular respiration, which then converts into energy known as ATP. When there is a lot of ATP and Glucose, the liver converts it into glycogen.

Cancer cells displayed marked alterations in pro-growth signaling pathways and key metabolic pathways relative to non-tumorigenic differentiated cells, often due to loss of tumor suppressor genes and oncogenic driver mutations. The remodeled signaling and metabolic profiles of cancer cells support not only their aberrant proliferation, but also their survival. Further factors such as intra-tumoral heterogeneity, altered redox status, and epigenetic modifications all contribute to the ability of certain tumors to develop drug resistance and persist under standard treatments.

Cancer is the second most prominent cause of death in the United States. In the year 2016, it is predicted that 595,690 Americans will die from this disease.12 Caner is defined as an uncontrollable division of cells in the body that spreads into surrounding tissue. This rapid division of cells can occur almost anywhere in the human body. The cancer treatments currently available in modern medicine include a combination of chemotherapy, radiation, and surgery. Recently scientists have discovered that there could be another way to battle this epidemic. There proves to be a strong correlation between this rapid cell division that is seen in cancer patients with the metabolism of glucose. Glucose provides the energy needed for these cells to continue to rapidly divide and develop new cells. This could mean that nutrition may be a very valuable weapon in the war against cancer. 5 A high fat, low carbohydrate diet, also known as a ketogenic diet, has been successful in the clinical world for patients with uncontrollable seizures, but it may now pose as a viable resource to assist in cancer recovery. By restricting carbohydrates through diet, thus starving the cancer cell of glucose, we may be able to slow or terminate the spread of these cancer cells. The objective of this paper will be to give a better insight on how a Ketogenic diet may aid in delaying or terminating cancer.

The AAP is a potential trigger of cytochrome P450 that induced the high reactive quinone-imine production. This matches with sulphahydryl groups in proteins and result in rapid depletion to intracellular glutathione(35). Generally, one parts of the potential intracellular antioxidant defensive system is glutathione that consumes the singlet oxygen, superoxide and hydroxyl radicals(36). Enhancing of intracellular flux of oxygen free radicals results from glutathione depletion leads to oxidative stress in hepatocytes(36). The increasing the serum levels of GOT, GPT and ALP have been attributed to the structural integrity hepatic damage(37). In liver tissue, GOT and GPT are located in cytosol and mitochondria. In following of liver damage, hepatocyte transport function disturbed

The liver synthesizes glycogen from glucose which is process called glycogenesis. After that process, glycogen or glucose must be converted to glucose-6-phosphate before energy can be generated. Glucose-1-phosphate is converted to glucose-6-phosphate. Glycolysis requires 10 to 12 enzymatic reactions for the breakdown of glycogen to pyruvic acid, which is then converted to lactic acid. All steps in the pathway and all of the enzymes involved operate within the cell cytoplasm. (Wilmore, J.) For each glycogen broken down, the result is 3 molecules of ATP.

Through many cancer researches in the last decades, it was found that cancer cells often use glucose more voraciously and quite differently from normal cells. Therefore, many researchers and pharmaceutical companies have thought that the nutrient supply and deprivation of the cancer cells will potentially be the next target in disrupting the metabolism of cancer cells.

FDG is a non-physiological analogue of glucose that once injected, is taken up by cell membrane glucose receptors (Mainly, the glucose transporter-1 molecule, GLUT-1) which transport it into the intracellular compartment, where it is phosphorylated into FDG-6-phosphate by the enzymatic action of hexokinase. Cancer cells show increased uptake of glucose (due to an overexpression of glucose transporter proteins) and increased rate of glycolysis. However, following phosphorylation by hexokinase, FDG becomes trapped in the cancer cell, failing to undergo further metabolism due to down-regulation of phosphatase [1] .

Cellular respiration is the method by which an organism converts carbon based fuel and oxygen into adenosine triphosphate (ATP) the source of energy for cells, carbon dioxide and water (Open Learning Initiative, 2015, pg.140; Respiration, Cellular, 2014, pg.3737). Moreover, the cellular respiration process occurs in three major steps: glycolysis, the Krebs cycle, and electron transport (Respiration, Cellular, 2014, pg.3737). During the glycolysis stage, inside the mitochondria of the cell, glucose is broken down into pyruvate (a three carbon sugar) which releases energy in the form of a net gain of two ATP molecules (four total are produced but two are consumed during the process) (Open Learning Initiative, 2015, pg.141; Respiration, Cellular, 2014, pg.3737). Next, during the Krebs cycle, inside the mitochondrial cellular matrix, the pyruvate from the previous cycle is transformed into acetyl CoA after which it undergoes a process where the acetyl CoA is converted into carbon dioxide and water via oxidization resulting in the

The ability of p53 to regulate metabolism is also associated with the ability to regulate cellular ROS levels. As previously mentioned, p53 can either remove damaged cells that have suffered sustained oxidative stress, or limit levels of ROS in order to lower oxidative stress and consequently, potential cell damage. Through the regulation of carbohydrate and lipid metabolism, p53 is able to influence the response to ROS accordingly. By driving the expression of TIGAR and promoting PPP activity, p53 can increase the production of NAPDH, which can be used to generate the cellular antioxidant GSH (Bensaad 2006). Moreover, at the expense of nucleotide synthesis, p53 can also promote GSH synthesis following serine starvation, thereby lowering ROS

Presently there is a proposition indicating the ketogenic diet as a method to starve cancer cells of their primary fuel, glucose (sugar), which will eventually kill the cancer cell . In other words, healthy cells can live on a diet of fats, but not on carbohydrates, cancer cells, however, will survive with glucose or what is called blood sugar because Brain cancer cells depend on glucose for growth and survival. When the body does not have enough glucose for energy, it burns stored fats instead; this result in a build-up of acids called ketones within the body. With that, the ketogenic diet has been proposed as a complementary therapy for the treatment of malignant

“Western blot analysis of p53 and Bax in mitochondrial fraction (left) and examination of apoptosis (right) in mouse skin epidermal tissues. Succinate dehydrogenase subunit B (SDHB) served as the loading control. The levels of p53/Bax were normalized to that of SDHB. Statistical analysis was performed using one-way ANOVA (for multiple group comparison) followed by Newman-Keuls post-test. Ctrl, basal diet; Veh, vehicle control (DMSO); Pro, Protandim. *, p