Gluconeogenesis and Fasting
Discuss about the Astrocytic Glycogenolysis for Mechanisms and Functions.
The body of academic literature and scientific research indicates that there is a primary difference between starvation and fasting. Starvation is simply the reductions in caloric energy intake within the human body (Thomas 2007). Fasting, on the other hand, comes by free will and is defined by abstaining from all or some kinds of foods or drinks for a short period of time (Sidhu and Naugler, 2012). Predominantly, the majority of religions believe that fasting is good for the soul (Trepanowski and Bloomer, 2010). There is no doubt that reduction in one’s diet could be beneficial in different aspects. In saying that however, the human body is essentially a mechanical machine that need certain nutrients, proteins and carbohydrates to function. One who is in a fasting or starving state lacks these essentials ingredients. It suffices to say, that if one enters into the state of fasting or starvation, there exists a change in the biochemical and physiological responses in the body. Following this, the main causes of starvation originate from medical or circumstantial causes. Medical causes of starvation include, but are not limited to, Anorexia, Bulimia Nervosa, Eating Disorders, Celiac Disease, Major Depressive Disorder, Diabetes mellitus and Digestive disease. The main cases of circumstantial causes are specifically motivated by political, social and economic interests. These motivations can manifest in different forms, such as extreme diets, domestic violence and abuse, or famine which arises from political strife, warfare and poverty.
Firstly, humans need to maintain proper blood glucoses levels above a certain concentration in order to survive, which is essentially part of homeostasis (Gray et al., 2015). For example, let’s start by having a mini case of starvation three or four hours after a meal your blood glucose levels begin to drop so what your body begins to do is quickly turns to its glycogen stores in the liver, the only main issue with this is that our glycogen stores in the body only last us around 24hrs are this the blood glucose levels begin to drop and the body need different methods to try bring that blood glucose levels back up. This is primarily where the metabolic pathways in gluconeogenesis comes into play this is the pathway where we produce new glucose. These new glucose molecules are produced from non-carbohydrate pre curser molecules (Hatting et al., 2018). Gluconeogenesis in humans involves the synthesis of glucose and glycogen from lactate, also pyruvate, glycerol and certain amino acids. The liver is the main organ for gluconeogenesis while the kidneys also become an important site during starvation.
Ketosis and Energy Production
The body is always in the process if maintaining a balanced level of blood glucose to ensure that enough of it is available especially for the vital organs like the brains tissues. Gluconeogenesis refers to a pathway or process in which glucose molecules are synthesized from non-carbohydrate precursors. Gluconeogenesis occurs primarily in the liver although other sites including the kidneys can support this process (Mithieux et al., 2017). for instance, under tough starvation conditions, it is the cortex of the kidneys which supports gluconeogenesis. However, majority of the glucose made by the renal cortex is used by the renal medulla, while a few amounts enters into the blood stream. Most of the processes in gluconeogenesis are similar to glycolysis. The enzymes in the two reverse processes are highly regulated so that at any given time only one process occurs and not both. The most common amino acids used for synthesis of glucose are alanine. Alanine is produced in the muscle tissues from other amino acids as well as glucose. For pyruvate to be used as a precursor, it must be sourced from anaerobic glycolysis in some tissues like erythrocytes, muscles and fat adipose tissues. On the other hand, glycerol as a raw material is sourced from adipose stores of the fatty acids, while amino acids are generated from the amino acid pools of the muscle tissues.
This is a metabolic process which takes place in the body especially when the body does not have enough energy to sustain its activities and maintain hemostasis. In ketosis, the body burns down the stored fats leading to a buildup of ketones in the body cells (Paoli et al., 2015). As the levels of the ketones build up, so does the acidity of the blood increases too. In some cases, there are some people who observe a ketogenic or low carbohydrate diet so as to lose weight by using fats to produce energy. When glucose amounts are not sufficient in the body, stored fats are broken down to meet the body needs of glucose. In the end, ketones are formed as byproducts and are later eliminated in the urine. In low amounts, ketones signal that the body is breaking down fats, but at high amounts, they become poisonous sue to the accumulation of ketone and gives rise to ketoacidosis. This process is initiated when the body is undergoing starvation and fasting leading to low or no glucose supply in the diet (LaManna et al., 2017).
Muscles and Blood Sugar Regulation
Ketosis produces energy which can serve some vital organs, more so the brain. Three days after the starvation, the liver produces ketone bodies such as acetoacetate and hydroxybutyrate from acetyl coA. This is because the Krebs cycle is unable to utilize all the available acetyl-coA molecules produced from fatty acids degradation. At the same time, since during starvation the gluconeogenesis is active, this pathway ends up consuming the oxaloacetate which would be coupled to acetyl CoA in Krebs cycle. The brain uses considerable amounts of acetoacetate since glucose is unavailable during fasting and starvation (Cunnane et al., 2016). Following about three days of starvation, all the energy requirements by the brain are met by ketones. In some cases, the heart can also use ketone bodies as a sources of metabolic fuel.
The muscles are involved in the regulation of blood sugar levels. When there is insulin produced by the cells, it enables the muscles to draw glucose from blood thus lowering the blood glucose levels. However, in the event that the body does not have enough insulin levels, glucose in the blood cannot enter the cells to provide them with energy (Sylow et al., 2017). The insulin receptor complex initiates the cells to take up glucose in the blood. A well fed muscle contains about one percent of its weight as glycogen. The muscles contain about four times content of glycogen as the liver. However, the muscle glycogen is not directly available to the cells because the muscles lack the enzyme glucose-6-ohosphatase necessary for obtaining glucose molecules for energy production. When muscles are engaging in activities, the glycogen is converted into lactate and then into blood glucose. During starvation and fasting, the muscles adapt to this condition through the Cori cycles in order to make glucose molecules. In the Cori cycle, the muscles through anaerobic glycolysis produces which is then converted into pyruvate in the liver for the synthesis of glucose (Martínez-Reyes and Chandel, 2017).
The conversion of lactate to pyruvate is facilitated by the enzyme lactate dehydrogenase. The pyruvate then becomes the substrate for gluconeogenesis. Synthesis of glucose requires the input of energy in the form of ATP which is supplied by a number of sources. The advantage of Cori cycle is that it preserves the number of carbon atoms in a molecule. In this case, a six carbon sugar is split into two molecules of three-carbon molecules known as lactate which then converted into two three-carbon molecules known as pyruvate. Once glucose is synthesized in the liver, it diffuses out of the liver cells and into the blood stream whereby it is transported into the skeletal muscle cells and the Cori cycle becomes complete. However, for glucose to be made available in the cells and in enough concentrations, the role of glucose transporters becomes quite significant. The glucose transporter type 4 has been documented the most common type of glucose transporter which is produced in the muscles, adipose tissues and liver cells.
The Role of Glucose Transporters
Since the lymphatic system consist of the body immune system that offers defense, it requires a constant supply of glucose to make energy. in the post absorptive state, the dietary lipids are packaged into chylomicrons and transporters in to the blood through the lymphatic system. Since it is a fed state, insulin is secreted, a major regulator of biomolecules metabolism. In intermittent fasting, the body breaks down fats while excreting some to the lymphatic system (Balmer and Hess, 2017). In the event that the lymphatic system becomes congested, it becomes difficult to remove fats from the body by slowing down the loss of weight. If the reserve fats in the cells are mobilized especially during fasting, it is transported to some extent by the lymphatic system. During fasting, the lymph contains fats in varied amounts whereby the amount fat in the lymph depends on the date of nutrition, duration of fasting, and the age of the organism among many other factors. The fats present in the lymph during fasting is thought to come from blood fats which have been filtered through the blood capillaries directly into the lymphatic system (Maekawa et al., 2015). The lymph contains higher amounts of fats as compared to the blood and thus only trace amounts for body fats come from the blood.
The lymphatic system requires ATP from glucose molecules in order to play the lymphocytes roles. The T cells which are part of the lymphatic system requires a constant supply of energy from glucose. However, the naïve cells need extrinsic function of the cytokines in order to maintain the continued uptake of glucose for the normal cells activities. In the lymphocytes, the glucose molecules when available are converted to pyruvate with net release of energy. However, during starvation and fasting, the pyruvate is used to make energy whereby it is converted to lactate (Teuwen et al., 2017). Then lactate undergoes a number of processes to produce NAD+, an electrical acceptor from NADH. These electrons fuel other pathways to produce energy required for the lymphatic cells. Moreover, in the absence of glucose, or during the resting state of the lymphatic system, these cells derives energy through oxidative phosphorylation which oxygen independent. The oxidative phosphorylation involves two stages; first is the conversion of pyruvate and fatty acids to acetyl CoA molecules, a process carried by molecules with reducing power, i.e. NADH and FADH2 through the electron transport chain. Therefore, it is necessary that there is a close monitoring of glucose levels in order to ensure that a sustained monitoring to maintain an immune hemostasis (Gomes et al., 2016). It is also necessary to gain some understanding concerning so as to be able to understand the homeostasis in the body through gaining a detailed understanding and the pathways involved in the various therapeutic developments. For obvious reasons, once there is a lack of proper blood glucose supply; or in cases where the control is not closely monitored, then there could be problems in the synthesis and function of the lymphatic cells. In terms of glucose transporters, it is necessary to note that the lymphocytes do not have the glucose transporter type 4 but instead has glucose transporter type 1.
The Importance of the Lymphatic System
Another route via which the body adapts to starvation or fasting s through glycogenolysis. In this cases, the stored glucose in form of glycogen is broken down into individual glucose units. The breakdown of glycogen takes place in three major steps. From glycogen, the glucose-1-phosphate is formed so that the glycogen molecules are modified to make them tready for another reaction (Hertx et al., 2015). Then glucose-1-phosphate is converted into glucose-6- phosphate the resulting glucose -6-phosphate gas three fates. One’s that it can enter the glycolysis to make energy, it can enter the pentose phosphate pathway to form NADPH and five-carbon sugars. Glucose-6-phosphate can also be converted into free glucose molecules. However, two hormones namely; insulin and epinephrine play vital roles in glycogenolysis (Gibbs, 2016). For instance, glucagon, which is produced by the pancreas is necessary for a response to low blood sugar especially during fating and starvation. On the other hand, epinephrine is a hormone produced by the adrenal glands in response to some form of threat, stress or both. The two hormones function by causing the stimulation of the enzyme glycogen phosphorylase where the glucose molecules are hydrolyzed from glycogen stored in the tissues. In the end, glucose molecules are formed, which if not immediately not needed by the cells, they can remove in blood circulation.
In summary, humans essentially need to maintain homeostasis in order to survive once these boundaries shift away from this equilibrium. The body goes into a state where it attempts to try bring those levels back up or down. In the case of starving and fasting, the blood glucose levels drop and the body does everything in its power to bring them back up. This can effectively occur either through metabolic pathways or using it from other organs or tissues. During fasting and starvation, the bodies of animals and human beings must adapt to some physiological changes. These adaptations are meant to make the bodies adapt to the glucose supply changes but at the same time be able to support the normal cell functions. Thus the body responds to fasting and starvation through increased burning of fats and other macromolecules which are later oxidized to form energy. In other cases, the muscle tissues are consumed so as to make enough energy to keep the cells alive. In human beings, upon the exhaustion of the remaining contents in the gastrointestinal tract, the body switches to fats and amino acids metabolism. Therefore, the process of hemostasis control clearly indicates that the control of the adaptation strategies during fasting or starvation involves an interplay between hormones, enzymes or both. In the end the cells make energy via other means until the condition is restored back.
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