In Silico Evidence For Gluconeogenesis From Fatty Acids In Humans
Abstract The question whether fatty acids can be converted into glucose in humans has a long standing tradition in biochemistry, and the expected answer is “No”. Using recent advances in Systems Biology in the form of large-scale metabolic reconstructions, we reassessed this question by performing a global investigation of a genome-scale human metabolic network, which had been reconstructed on the basis of experimental results. By elementary flux pattern analysis, we found numerous pathways on which gluconeogenesis from fatty acids is feasible in humans. On these pathways, four moles of acetyl-CoA are converted into one mole of glucose and two moles of CO2. Analyzing the detected pathways in detail we found that their energetic requirements potentially limit their capacity. This study has many other biochemical implications: effect of starvation, sports physiology, practically carbohydrate-free diets of inuit, as well as survival of hibernating animals and embryos of egg-laying animals. Moreover, the energetic loss associated to the usage of gluconeogenesis from fatty acids can help explain the efficiency of carbohydrate reduced and ketogenic diets such as the Atkins diet. Author Summary That sugar can be converted into fatty acids in humans is a well-known fact. The question whether the reverse direction, i.e., gluconeogenesis from fatty acids, is also feasible has been a topic of intense debate since the end of the 19th century. With the discovery of the glyoxylate shunt that allows this conversion in some bacteria, plants, fungi and nematodes it has been considered infeasible in humans since the corresponding enzymes could not be detected. However, by this finding only a single route for gluconeogenesis from fatty acids has been ruled out. To address the question Continue reading >>
The Difference Between Glycolysis & Gluconeogenesis
The Difference Between Glycolysis & Gluconeogenesis By Noelle Thompson; Updated March 13, 2018 Glucose is the main source of energy for all biochemical reactions in the human body. It is converted through a series of metabolic pathways into energy-producing molecules. The levels of glucose in cells are maintained through a balance of breaking down glucose and synthesizing new glucose, as necessary through the pathways of glycolysis and gluconeogenesis. Glucose can also be stored by the cells for later use. Glucose is obtained by breaking down carbohydrates from ingested food. Through a series of metabolic reactions, glucose is broken down into various intermediate products, before eventually producing molecules of adenosine triphosphate, or ATP. ATP serves as the main energy source in the body and is responsible for driving most of the biochemical reactions in a living organism. Cells in critical organs, such as the brain and muscles, require high amounts of energy, and therefore high amounts of glucose, to perform their normal functions. Glycolysis is the initial metabolic pathway through which glucose is broken down. Each molecule of glucose is broken down into two molecules of pyruvate, as well as two molecules of ATP, and two molecules of the coenzyme NAD. The pyruvate molecules are further broken down during another series of metabolic reactions known as the Krebs cycle. The Krebs cycle yields more ATP and NADH molecules, as well as another coenzyme, FADH2. The coenzymes can enter the electron transport chain, where they are converted into ATP. Each molecule of glucose yields a total of 36 ATP molecules. Gluconeogenesis is essentially the reverse of glycolysis, involving the synthesis of glucose from two pryuvate molecules. Gluconeogenesis occurs primarily in the Continue reading >>
Can Fats Be Turned Into Glycogen For Muscle?
The amount of fat in the average diet and the amount of stored fat in the average body make the notion of converting that fat into usable energy appealing. Glycogen, a form of energy stored in muscles for quick use, is what the body draws on first to perform movements, and higher glycogen levels result in higher usable energy. It is not possible for fats to be converted directly into glycogen because they are not made up glucose, but it is possible for fats to be indirectly broken down into glucose, which can be used to create glycogen. Relationship Between Fats and Glycogen Fats are a nutrient found in food and a compound used for long-term energy storage in the body, while glycogen is a chain of glucose molecules created by the body from glucose for short-term energy storage and utilization. Dietary fats are used for a number of functions in the body, including maintaining cell membranes, but they are not used primarily as a source of fast energy. Instead, for energy the body relies mostly on carbohydrates, which are converted into glucose that is then used to form glycogen. Turning Fats Into Glucose Excess glucose in the body is converted into stored fat under certain conditions, so it seems logical that glucose could be derived from fats. This process is called gluconeogenesis, and there are multiple pathways the body can use to achieve this conversion. Gluconeogenesis generally occurs only when the body cannot produce sufficient glucose from carbohydrates, such as during starvation or on a low-carbohydrate diet. This is less efficient than producing glucose through the metabolizing of carbohydrates, but it is possible under the right conditions. Turning Glucose Into Glycogen Once glucose has been obtained from fats, your body easily converts it into glycogen. In gl Continue reading >>
We Really Can Make Glucose From Fatty Acids After All! O Textbook, How Thy Biochemistry Hast Deceived Me!
Biochemistry textbooks generally tell us that we can’t turn fatty acids into glucose. For example, on page 634 of the 2006 and 2008 editions of Biochemistry by Berg, Tymoczko, and Stryer, we find the following: Animals Cannot Convert Fatty Acids to Glucose It is important to note that animals are unable to effect the net synthesis of glucose from fatty acids. Specficially, acetyl CoA cannot be converted into pyruvate or oxaloacetate in animals. In fact this is so important that it should be written in italics and have its own bold heading! But it’s not quite right. Making glucose from fatty acids is low-paying work. It’s not the type of alchemy that would allow us to build imperial palaces out of sugar cubes or offer hourly sweet sacrifices upon the altar of the glorious god of glucose (God forbid!). But it can be done, and it’ll help pay the bills when times are tight. All Aboard the Acetyl CoA! When we’re running primarily on fatty acids, our livers break the bulk of these fatty acids down into two-carbon units called acetate. When acetate hangs out all by its lonesome like it does in a bottle of vinegar, it’s called acetic acid and it gives vinegar its characteristic smell. Our livers aren’t bottles of vinegar, however, and they do things a bit differently. They have a little shuttle called coenzyme A, or “CoA” for short, that carries acetate wherever it needs to go. When the acetate passenger is loaded onto the CoA shuttle, we refer to the whole shebang as acetyl CoA. As acetyl CoA moves its caboose along the biochemical railway, it eventually reaches a crossroads where it has to decide whether to enter the Land of Ketogenesis or traverse the TCA cycle. The Land of Ketogenesis is a quite magical place to which we’ll return in a few moments, but n Continue reading >>
Gluconeogenesis | Definition Of Gluconeogenesis By Medical Dictionary
Gluconeogenesis | definition of gluconeogenesis by Medical dictionary the synthesis of glucose from noncarbohydrate sources, such as amino acids and glycerol. It occurs primarily in the liver and kidneys whenever the supply of carbohydrates is insufficient to meet the body's energy needs. Gluconeogenesis is stimulated by cortisol and other glucocorticoids and by the thyroid hormone thyroxine. Formerly called glyconeogenesis. /gluconeogenesis/ (glooko-neo-jen-sis) the synthesis of glucose from molecules that are not carbohydrates, such as amino and fatty acids. The formation of glucose, especially by the liver, from noncarbohydrate sources, such as amino acids and the glycerol portion of fats. gluconeogenetic (--j-ntk) adj. the formation of glucose from glycerol and proteins rather than from carbohydrates. Also called glyconeogenesis . The formation of glucose from noncarbohydrate moleculeseg, amino acids, lactic acid The formation of glucose from non-carbohydrate sources, especially from AMINO ACIDS from protein. GLUCOCORTICOID hormones stimulate gluconeogenesis. the process by which PYRUVIC ACID (pyruvate) is converted to GLUCOSE . This is not the exact reversal of GLYCOLYSIS . Three of the reactions of glycolysis are irreversible and it is in these three that gluconeogenesis differs. In the CELL gluconeogenesis is normally more active when there is little need for ATP . The process meets the needs of the body for glucose when CARBOHYDRATE is not available in adequate amounts from the diet. Non-carbohydrates, such as FAT and PROTEIN , can be converted into glucose, notably in the LIVER and KIDNEY . synthesis of glucose from non-carbohydrate precursors mainly in the liver and to a smaller extent in the renal cortex. Precursors include pyruvate, lactate, glycerol and th Continue reading >>
Why Can't Fat Produce Glucose?
Tousief Irshad Ahmed Sirwal Author has 77 answers and 106.2k answer views Acetyl CoA is NOT a substrate for gluconeogenesis in animals 1. Pyruvate dehydrogenase reaction is irreversible. So, acetyl CoA cannot be converted back to pyruvate. 2. 2C Acetyl CoA enters the TCA cycle by condensing with 4C oxaloacetate. 2 molecules of CO2 are released & the oxaloacetate is regenerated. There is no NET production of oxaloacetate. Animals cannot convert fat into glucose with minimal exceptions 1. Propionyl CoA derived from odd chain fatty acids are converted to Succinyl CoA Glucogenic 2. Glycerol derived from triglycerides are glucogenic. Answered Mar 26, 2017 Author has 942 answers and 259.1k answer views Yijia Xiong pointed out that the glycerol portion of triglycerides (fats) can indeed be converted to glucose. It is not so energy-inefficient that it is avoided by our bodies. If nutritionally, we are in a gluconeogenesis mode (building up glucose stores rather than consuming them), glycerol would be a perfectly acceptable precursor. However, I think the original question had more to do with the vast bulk of the triglycerides that are not glycerol, but are fatty acids. And it is true that we cant produce glucose from fatty acids. The reason is that the catabolic reactions of fatty acids break off two carbon atoms at a time as Acetyl-CoA. But our metabolic suite of pathways has no way to convert a two-carbon fragment to glucose. The end product of glycolysis is pyruvate, a three-carbon compound. Pyruvate can be back-synthesized into glucose. But the committing reaction for the Krebs cycle is the pyruvate dehydrogenase step, forming acetyl-CoA. That reaction is not reversible. Once pyruvate loses a carbon atom, it cant go back. The three main macronutrients are carbohydrates, pr Continue reading >>
Insulin And Glucagon
Acrobat PDF file can be downloaded here. The islets of Langerhans The pancreatic Islets of Langerhans are the sites of production of insulin, glucagon and somatostatin. The figure below shows an immunofluorescence image in which antibodies specific for these hormones have been coupled to differing fluorescence markers. We can therefore identify those cells that produce each of these three peptide hormones. You can see that most of the tissue, around 80 %, is comprised of the insulin-secreting red-colored beta cells (ß-cells). The green cells are the α-cells (alpha cells) which produce glucagon. We see also some blue cells; these are the somatostatin secreting γ-cells (gamma cells). Note that all of these differing cells are in close proximity with one another. While they primarily produce hormones to be circulated in blood (endocrine effects), they also have marked paracrine effects. That is, the secretion products of each cell type exert actions on adjacent cells within the Islet. An Introduction to secretion of insulin and glucagon The nutrient-regulated control of the release of these hormones manages tissue metabolism and the blood levels of glucose, fatty acids, triglycerides and amino acids. They are responsible for homeostasis; the minute-to-minute regulation of the body's integrated metabolism and, thereby, stabilize our inner milieu. The mechanisms involved are extremely complex. Modern medical treatment of diabetes (rapidly becoming "public enemy number one") is based on insight into these mechanisms, some of which are not completely understood. I will attempt to give an introduction to this complicated biological picture in the following section. Somewhat deeper insight will come later. The Basics: secretion Let us begin with two extremely simplified figur Continue reading >>
Glucose Can Be Synthesized From Noncarbohydrate Precursors - Biochemistry - Ncbi Bookshelf
Glucose is formed by hydrolysis of glucose 6-phosphate in a reaction catalyzed by glucose 6-phosphatase. We will examine each of these steps in turn. 16.3.2. The Conversion of Pyruvate into Phosphoenolpyruvate Begins with the Formation of Oxaloacetate The first step in gluconeogenesis is the carboxylation of pyruvate to form oxaloacetate at the expense of a molecule of ATP . Then, oxaloacetate is decarboxylated and phosphorylated to yield phosphoenolpyruvate, at the expense of the high phosphoryl-transfer potential of GTP . Both of these reactions take place inside the mitochondria. The first reaction is catalyzed by pyruvate carboxylase and the second by phosphoenolpyruvate carboxykinase. The sum of these reactions is: Pyruvate carboxylase is of special interest because of its structural, catalytic, and allosteric properties. The N-terminal 300 to 350 amino acids form an ATP -grasp domain ( Figure 16.25 ), which is a widely used ATP-activating domain to be discussed in more detail when we investigate nucleotide biosynthesis ( Section 25.1.1 ). The C -terminal 80 amino acids constitute a biotin-binding domain ( Figure 16.26 ) that we will see again in fatty acid synthesis ( Section 22.4.1 ). Biotin is a covalently attached prosthetic group, which serves as a carrier of activated CO2. The carboxylate group of biotin is linked to the -amino group of a specific lysine residue by an amide bond ( Figure 16.27 ). Note that biotin is attached to pyruvate carboxylase by a long, flexible chain. The carboxylation of pyruvate takes place in three stages: Recall that, in aqueous solutions, CO2 exists as HCO3- with the aid of carbonic anhydrase (Section 9.2). The HCO3- is activated to carboxyphosphate. This activated CO2 is subsequently bonded to the N-1 atom of the biotin ring to Continue reading >>
Evolving Health: Why Can't We Convert Fat To Glucose?
As evident by many sugar-laden soda pop "potbellies" of North America, lipogenesis can obviously occur from drinking and eating too much sugar (1). Wouldnt it be just grand to reverse the process and be able to lose all that fat via gluconeogenesis? Unfortunately mammals do not have the ability to synthesize glucose from fats (1). The fact is that once glucose is converted to acetyl coA there is no method of getting back to glucose. The pyruvate dehydrogenase reaction that converts pyruvate to acetyl CoA is not reversible (1p252). Because lipid metabolism produces acetyl CoA via beta-oxidation, there can be no conversion to pyruvate or oxaloacetate that may have been used for gluconeogenesis (1p252). Further, the two carbons in the acetyl CoA molecule are lost upon entering the citric acid cycle (1p252). Thus, the acetyl CoA is used for energy (1p252). There are some fatty acids that have an odd number of carbon atoms that can be converted to glucose, but these are not common in the diet (1p253). Maybe they should be made more common. Do they taste good? 1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009. Continue reading >>
What Is Gluconeogenesis? How Does Does It Control Blood Sugars?
What is gluconeogenesis? How does does it control blood sugars? by breaknutrition | Sep 12, 2017 | Ketogenic Diets | 9 comments Step into the low-carb world and soon enough youll hear the term GlucoNeoGenesis. GNG for short, is your bodys ability to construct glucose, a kind of sugar, out of molecules that arent glucose. It does this to ensure that, if you dont eat any carbs, the cells in your body that need glucose will still get enough of it. Its one reason why humans are so good at fasting or delaying death from starvation for weeks or months. We can meet our own need for glucose by producing it ourselves. What do I mean by cells in your body that need glucose? I mean a reliance on glucose to accomplish its basic physiological tasks over a long time maybe a lifetime. You then might ask, but is there a difference when meeting your glucose needs with GNG versus by eating carbs? Fair question. You could also ask although no one seems to is it better to meet your glucose needs through GNG than by eating carbs? Also a fair question I think but one people will most likely scoff at. These questions deserve more space than Im according them here, so theyll have to be wrestled with in a follow-up post. Background: why do we make our own glucose? As mentioned in the introduction, it helps us handle a lack of calories or carbohydrates but that can only be because at least some of our cells depend on glucose (or other monosaccharides ) to some significant degree. Most cells in your body do just fine using varying amounts of fatty acids, glucose, amino acids, lactate, ketones etc However, a few cell types well call obligate glucose users cant use any other fuel but glucose. Then there are what well call quasi obligate glucose users whose metabolisms are adapted to specialized fu Continue reading >>
What is gluconeogenesis? Gluconeogenesis is a metabolic pathway that leads to the synthesis of glucose from pyruvate and other non-carbohydrate precursors, even in non-photosynthetic organisms. It occurs in all microorganisms, fungi, plants and animals, and the reactions are essentially the same, leading to the synthesis of one glucose molecule from two pyruvate molecules. Therefore, it is in essence glycolysis in reverse, which instead goes from glucose to pyruvate, and shares seven enzymes with it. Glycogenolysis is quite distinct from gluconeogenesis: it does not lead to de novo production of glucose from non-carbohydrate precursors, as shown by its overall reaction: Glycogen or (glucose)n → n glucose molecules The following discussion will focus on gluconeogenesis that occurs in higher animals, and in particular in the liver of mammals. Why is gluconeogenesis important? Gluconeogenesis is an essential metabolic pathway for at least two reasons. It ensures the maintenance of appropriate blood glucose levels when the liver glycogen is almost depleted and no carbohydrates are ingested. Maintaining blood glucose within the normal range, 3.3 to 5.5 mmol/L (60 and 99 mg/dL), is essential because many cells and tissues depend, largely or entirely, on glucose to meet their ATP demands; examples are red blood cells, neurons, skeletal muscle working under low oxygen conditions, the medulla of the kidney, the testes, the lens and the cornea of the eye, and embryonic tissues. For example, glucose requirement of the brain is about 120 g/die that is equal to: over 50% of the total body stores of the monosaccharide, about 210 g, of which 190 g are stored as muscle and liver glycogen, and 20 g are found in free form in body fluids; about 75% of the daily glucose requirement, abou Continue reading >>
All Of The Information In These Notes
Cellular respiration is the enzymatic breakdown of glucose (C6H12O6) in the presence of oxygen (O2) to produce cellular energy (ATP): 1. Glycolysis: (Fig. 18-2) a ten-step process that occurs in the cytoplasm converts each molecule of glucose to two molecules of pyruvic acid (a 3-carbon molecule) an anaerobic process - proceeds whether or not O2 is present ; O2 is not required net yield of 2 ATP per glucose molecule net yield of 2 NADH per glucose (NADH is nicotine adenine dinucleotide, a co-enzyme that serves as a carrier for H+ ions liberated as glucose is oxidized.) The pyruvic acid diffuses into the inner compartment of the mitochondrion where a transition reaction (Fig. 18-3) occurs that serves to prepare pyruvic acid for entry into the next stage of respiration: (a) pyruvic acid ® acetic acid + CO2 (a waste product of cell metabolism) + NADH+ (b) acetic acid + co-enzyme A ® acetyl CoA 2. Citric Acid or TCA Cycle:(Fig. 18-3) occurs in the inner mitochondrial matrix the acetyl group detaches from the co-enzyme A and enters the reaction cycle an aerobic process; will proceed only in the presence of O2 net yield of 2 ATP per glucose molecule (per 2 acetyl CoA) net yield of 6 NADH and 2 FADH2 (FAD serves the same purpose as NAD) in this stage of cellular respiration, the oxidation of glucose to CO2 is completed 3. Electron Transport System: consists of a series of enzymes on the inner mitochondrial membrane electrons are released from NADH and from FADH2 and as they are passed along the series of enzymes, they give up energy which is used to fuel a process called chemiosmosis by which H+ ions are actively transported across the inner mitochondrial membrane into the outer mitochondrial compartment. The H+ ions then flow back through special pores in the membrane, a pr Continue reading >>
Lipogenesis is the process by which acetyl-CoA is converted to fatty acids. The former is an intermediate stage in metabolism of simple sugars, such as glucose, a source of energy of living organisms. Through lipogenesis and subsequent triglyceride synthesis, the energy can be efficiently stored in the form of fats. Lipogenesis encompasses both the process of fatty acid synthesis and triglyceride synthesis (where fatty acids are esterified to glycerol). The products are secreted from the liver in the form of very-low-density lipoproteins (VLDL). VLDL particles are secreted directly into blood, where they mature and function to deliver the endogenously derived lipids to peripheral tissues. Fatty acid synthesis Main article: Fatty acid synthesis Fatty acids synthesis starts with acetyl-CoA and builds up by the addition of two-carbon units. The synthesis occurs in the cytoplasm of the cell, in contrast to the degradation (oxidation), which occurs in the mitochondria. Many of the enzymes for the fatty acid synthesis are organized into a multienzyme complex called fatty acid synthase. The major sites of fatty acid synthesis are adipose tissue and the liver. Control and regulation Hormonal regulation Insulin is a peptide hormone that is critical for managing the body's metabolism. Insulin is released by the pancreas when blood sugar levels rise, and it has many effects that broadly promote the absorption and storage of sugars, including lipogenesis. Insulin stimulates lipogenesis primarily by activating two enzymatic pathways. Pyruvate dehydrogenase (PDH), converts pyruvate into acetyl-CoA. Acetyl-CoA carboxylase (ACC), converts acetyl-CoA produced by PDH into malonyl-CoA. Malonyl-CoA provides the two-carbon building blocks that are used to create l Continue reading >>
Does Fat Convert To Glucose In The Body?
Your body is an amazing machine that is able to extract energy from just about anything you eat. While glucose is your body's preferred energy source, you can't convert fat into glucose for energy; instead, fatty acids or ketones are used to supply your body with energy from fat. Video of the Day Fat is a concentrated source of energy, and it generally supplies about half the energy you burn daily. During digestion and metabolism, the fat in the food you eat is broken down into fatty acids and glycerol, which are emulsified and absorbed into your blood stream. While some tissues -- including your muscles -- can use fatty acids for energy, your brain can't convert fatty acids to fuel. If you eat more fat than your body needs, the extra is stored in fat cells for later use. Fat has more than twice as many calories per gram as carbs and protein, which makes it an efficient form of stored energy. It would take more than 20 pounds of glycogen -- a type of carbohydrate used for fuel -- to store the same amount of energy in just 10 pounds of fat. Your Body Makes Glucose From Carbs Almost all the glucose in your body originated from carbohydrates, which come from the fruit, vegetables, grains and milk in your diet. When you eat these carb-containing foods, your digestive system breaks them down into glucose, which is then used for energy by your cells. Any excess glucose is converted into glycogen, then stored in your muscles and liver for later use. Once you can't store any more glucose or glycogen, your body stores any leftover carbs as fat. Glucose is your brain's preferred source of energy. However, when glucose is in short supply, your brain can use ketones -- which are derived from fat -- for fuel. Since your brain accounts for approximately one-fifth of your daily calori Continue reading >>
Biosynthesis Of Fat
Glucose is both stored energy for living things and the precursor to other biomolecules. Respiration is an enzyme catalyzed process that releases energy to the cells. From an energy standpoint, it is identical to the combustion reaction of glucose and it releases 6 equivalents of carbon dioxide and 6 equivalents of water for every equivalent of glucose. In biosynthetic reactions, the glucose is broken down into 2, three-carbon pieces. One equivalent of carbon dioxide is lost for every one of the 3-carbon units. Four carbons of the original six-carbon glucose molecule are used in the synthesis of fatty acids. It's a complicated process and we won't go over the whole thing in detail but let's look at the first step. That is the base-catalyzed isomerization of glucose to fructose. As you can see, the first step is a base (basic site in a protein) removes a proton from C2 of the glucose molecule. The pair of electrons from the former C-H bond migrate to form a C-C pi bond and another pair of electrons (from the C=O group) migrates to the carbonyl oxygen. The oxygen anion is basic and abstracts a proton from water. As a new C-O double bond forms on C2, the proton from the C2 hydroxy group migrates to C1. All the acids we've talked about so far have had an acidic hydrogen attached to either an oxygen or nitrogen atom. The electronegative oxygen or nitrogen atoms can stabilize the negative charge in the conjugate base. In the isomerization of glucose, a C-H unit provides the acidic hydrogen. How can this happen? Electron-withdrawing groups adjacent to the carbon make that carbon very electron-poor and allow it to stabilize the conjugate base. Stabilizing the conjugate base makes the acid stronger. A typical saturated alkane, such as ethane, is not at all basic. It has a pKa o Continue reading >>