diabetestalk.net

Can You Synthesize Glucose From Fatty Acids?

In Silico Evidence For Gluconeogenesis From Fatty Acids In Humans

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 >>

Gluconeogenesis

Gluconeogenesis

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 >>

Why Can't Animals Turn Fatty Acids Into Glucose?

Why Can't Animals Turn Fatty Acids Into Glucose?

Animals can’t turn fatty acids into glucose because fatty acids are metabolized 2 carbons at a time into the acetyl units of acetyl-CoA, and we have no enzymes to convert acetyl-CoA into pyruvate or any other metabolite in the gluconeogenesis pathway. Essentially, as I tell my students, the pyruvate dehydrogenase reaction is crossing the Rubicon: once it’s done, you can’t go back. The oxidative decarboxylation of pyruvate is irreversible, and there is no reverse bypass in animal cells. Acetyl-CoA of course enters the Krebs cycle, which ends with oxaloacetate, which is on the gluconeogenic pathway, but the Krebs cycle starts by reacting acetyl-CoA with OAA, and thus OAA production is balanced by OAA consumption: there is no net conversion of acetyl-CoA into OAA. Plants, fungi, and some microbes do have a way to do this: a bypass in the Krebs cycle called the glyoxylate cycle. Isocitrate, instead of being oxidized to alpha-ketoglutarate, is split into succinate and glyoxylate (HC(O)-COO), by an enzyme called isocitrate lyase. The glyoxylate reacts with another acetyl-CoA to form malate, in a reaction catalyzed by malate synthase. The succinate and malate both undergo their usual reactions in the Krebs cycle, resulting in the formation of two oxaloacetates. Thus the cell achieves a net conversion of two acetyl-CoA into OAA, and the OAA can be used for gluconeogenesis. This allows, among other things, plant seeds to store energy and carbon in the form of fats, but use them to create glucose and thus cellulose for cell walls when the seed germinates into a sprout. If we had isocitrate lyase and malate synthase, we could do this trick to, and diabetics wouldn’t have to worry about ketoacidosis. But, we don’t. Edit: for the sake of accuracy, I should mention that fat Continue reading >>

Evolving Health: Why Can't We Convert Fat To Glucose?

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 >>

Principles Of Biochemistry/gluconeogenesis And Glycogenesis

Principles Of Biochemistry/gluconeogenesis And Glycogenesis

Gluconeogenesis (abbreviated GNG) is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids. It is one of the two main mechanisms humans and many other animals use to keep blood glucose levels from dropping too low (hypoglycemia). The other means of maintaining blood glucose levels is through the degradation of glycogen (glycogenolysis). Gluconeogenesis is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In animals, gluconeogenesis takes place mainly in the liver and, to a lesser extent, in the cortex of kidneys. This process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise and is highly endergonic. For example, the pathway leading from phosphoenolpyruvate to glucose-6-phosphate requires 6 molecules of ATP. Gluconeogenesis is often associated with ketosis. Gluconeogenesis is also a target of therapy for type II diabetes, such as metformin, which inhibits glucose formation and stimulates glucose uptake by cells. Lactate is transported back to the liver where it is converted into pyruvate by the Cori cycle using the enzyme lactate dehydrogenase. Pyruvate, the first designated substrate of the gluconeogenic pathway, can then be used to generate glucose. All citric acid cycle intermediates, through conversion to oxaloacetate, amino acids other than lysine or leucine, and glycerol can also function as substrates for gluconeogenesis.Transamination or deamination of amino acids facilitates entering of their carbon skeleton into the cycle directly (as pyruvate or oxaloacetate), or indirectly via the citric acid cycle. Whether fatty acids can be converted into glucose in animals has been a longst Continue reading >>

Why Can Fatty Acids Not Be Converted Into Glucose? : Mcat

Why Can Fatty Acids Not Be Converted Into Glucose? : Mcat

Rudeness or trolling will not be tolerated. Be nice to each other, hating on other users won't help you get extra points on the MCAT, so why do it? Do not post any question information from any resource in the title of your post. These are considered spoilers and should be marked as such. For an example format for submitting pictures of questions from practice material click here Do not link to content that infringes on copyright laws (MCAT torrents, third party resources, etc). Do not post repeat "GOOD LUCK", "TEST SCORE", or test reaction posts. We have one "stickied" post for each exam and score release day, contain all test day discussion/reactions to that thread only. Do not discuss any specific information from your actual MCAT exam. You have signed an examinee agreement, and it will be enforced on this subreddit. Do not intentionally advertise paid products or services of any sort. These posts will be removed and the user banned without warning, subject to the discretion of the mod team Learn More All of the above rules are subject to moderator discretion C/P = Chemical and Physical Foundations of Biological Systems CARS = Critical Analysis and Reasoning Skills B/B = Biological and Biochemical Foundations of Living Systems P/S = Psychological, Social, and Biological Foundations of Behavior Continue reading >>

Can Sugars Be Produced From Fatty Acids? A Test Case For Pathway Analysis Tools

Can Sugars Be Produced From Fatty Acids? A Test Case For Pathway Analysis Tools

Can sugars be produced from fatty acids? A test case for pathway analysis tools Department of Bioinformatics, 2Bio Systems Analysis Group, Friedrich-Schiller-Universitt Jena, Ernst-Abbe-Platz 2, 07743 Jena, Germany and 3School of Life Sciences, Oxford Brookes University, Headington, Oxford, OX3 0BP, UK *To whom correspondence should be addressed. Search for other works by this author on: Department of Bioinformatics, 2Bio Systems Analysis Group, Friedrich-Schiller-Universitt Jena, Ernst-Abbe-Platz 2, 07743 Jena, Germany and 3School of Life Sciences, Oxford Brookes University, Headington, Oxford, OX3 0BP, UK *To whom correspondence should be addressed. Search for other works by this author on: Department of Bioinformatics, 2Bio Systems Analysis Group, Friedrich-Schiller-Universitt Jena, Ernst-Abbe-Platz 2, 07743 Jena, Germany and 3School of Life Sciences, Oxford Brookes University, Headington, Oxford, OX3 0BP, UK Search for other works by this author on: Department of Bioinformatics, 2Bio Systems Analysis Group, Friedrich-Schiller-Universitt Jena, Ernst-Abbe-Platz 2, 07743 Jena, Germany and 3School of Life Sciences, Oxford Brookes University, Headington, Oxford, OX3 0BP, UK Search for other works by this author on: Bioinformatics, Volume 25, Issue 1, 1 January 2009, Pages 152158, Luis F. de Figueiredo, Stefan Schuster, Christoph Kaleta, David A. Fell; Can sugars be produced from fatty acids? A test case for pathway analysis tools, Bioinformatics, Volume 25, Issue 1, 1 January 2009, Pages 152158, Motivation: In recent years, several methods have been proposed for determining metabolic pathways in an automated way based on network topology. The aim of this work is to analyse these methods by tackling a concrete example relevant in biochemistry. It concerns the question wh Continue reading >>

Chapter 19 : Carbohydrate Biosynthesis

Chapter 19 : Carbohydrate Biosynthesis

Thus the synthesis of glucose from pyruvate is a relativelycostly process. Much of this high energy cost is necessary toensure that gluconeogenesis is irreversible. Under intracellularconditions, the overall free-energy change of glycolysis is atleast -63 kJ/mol. Under the same conditions the overallfree-energy change of gluconeogenesis from pyruvate is alsohighly negative. Thus glycolysis and gluconeogenesis are bothessentially irreversible processes under intracellularconditions. Citric Acid Cycle Intermediates and Many Amino Acids AreGlucogenic The biosynthetic pathway to glucose described above allows thenet synthesis of glucose not only from pyruvate but also from thecitric acid cycle intermediates citrate, isocitrate,-ketoglutarate, succinate, fumarate, and malate. All may undergooxidation in the citric acid cycle to yield oxaloacetate.However, only three carbon atoms of oxaloacetate are convertedinto glucose; the fourth is released as CO in the conversion ofoxaloacetate to phosphoenolpyruvate by PEP carboxykinase (Fig.19-3). In Chapter 17 we showed that some or all of thecarbon atoms of many of the amino acids derived from proteins areultimately converted by mammals into either pyruvate or certainintermediates of the citric acid cycle. Such amino acids cantherefore undergo net conversion into glucose and are calledglucogenic amino acids (Table 19-3). Alanine and glutamine makeespecially important contributions in that they are the principalmolecules used to transport amino groups from extrahepatictissues to the liver. After removal of their amino groups inliver mitochondria, the carbon skeletons remaining (pyruvate anda-ketoglutarate, respectively) are readily funneled intogluconeogenesis. In contrast, there is no net conversion of even-carbon fattyacids into gl Continue reading >>

Gluconeogenesis: Endogenous Glucose Synthesis

Gluconeogenesis: Endogenous Glucose Synthesis

Reactions of Gluconeogenesis: Gluconeogenesis from two moles of pyruvate to two moles of 1,3-bisphosphoglycerate consumes six moles of ATP. This makes the process of gluconeogenesis very costly from an energy standpoint considering that glucose oxidation to two moles of pyruvate yields two moles of ATP. The major hepatic substrates for gluconeogenesis (glycerol, lactate, alanine, and pyruvate) are enclosed in red boxes for highlighting. The reactions that take place in the mitochondria are pyruvate to OAA and OAA to malate. Pyruvate from the cytosol is transported across the inner mitochondrial membrane by the pyruvate transporter. Transport of pyruvate across the plasma membrane is catalyzed by the SLC16A1 protein (also called the monocarboxylic acid transporter 1, MCT1) and transport across the outer mitochondrial membrane involves a voltage-dependent porin transporter. Transport across the inner mitochondrial membrane requires a heterotetrameric transport complex (mitochondrial pyruvate carrier) consisting of the MPC1 gene and MPC2 gene encoded proteins. Following reduction of OAA to malate the malate is transported to the cytosol by the malate transporter (SLC25A11). In the cytosol the malate is oxidized to OAA and the OOA then feeds into the gluconeogenic pathway via conversion to PEP via PEPCK. The PEPCK reaction is another site for consumption of an ATP equivalent (GTP is utilized in the PEPCK reaction). The reversal of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) reaction requires a supply of NADH. When lactate is the gluconeogenic substrate the NADH is supplied by the lactate dehydrogenase (LDH) reaction (indicated by the dashes lines), and it is supplied by the malate dehydrogenase reaction when pyruvate and alanine are the substrates. Secondly, one mo Continue reading >>

Gluconeogenesis

Gluconeogenesis

Not to be confused with Glycogenesis or Glyceroneogenesis. Simplified Gluconeogenesis Pathway Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. From breakdown of proteins, these substrates include glucogenic amino acids (although not ketogenic amino acids); from breakdown of lipids (such as triglycerides), they include glycerol (although not fatty acids); and from other steps in metabolism they include pyruvate and lactate. Gluconeogenesis is one of several main mechanisms used by humans and many other animals to maintain blood glucose levels, avoiding low levels (hypoglycemia). Other means include the degradation of glycogen (glycogenolysis)[1] and fatty acid catabolism. Gluconeogenesis is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms.[2] In vertebrates, gluconeogenesis takes place mainly in the liver and, to a lesser extent, in the cortex of the kidneys. In ruminants, this tends to be a continuous process.[3] In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise. The process is highly endergonic until it is coupled to the hydrolysis of ATP or GTP, effectively making the process exergonic. For example, the pathway leading from pyruvate to glucose-6-phosphate requires 4 molecules of ATP and 2 molecules of GTP to proceed spontaneously. Gluconeogenesis is often associated with ketosis. Gluconeogenesis is also a target of therapy for type 2 diabetes, such as the antidiabetic drug, metformin, which inhibits glucose formation and stimulates glucose uptake by cells.[4] In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs Continue reading >>

Gluconeogenesis Flashcards | Quizlet

Gluconeogenesis Flashcards | Quizlet

In general what happens if glucose levels are high? What happens if glucose levels are low? Synthesizing glucose from non-carbohydrate precursors What are the different precursors for gluconeogenesis? Precursors: pyruvate, lactate, propionate, glycerol, amino acids main way is from amino acids in protein degradation Multiple tissues, the liver is the major site. The kidneys and small intestine also undergo gluconeogenesis, in extended starvation there is a shift in gluconeogenesis from liver to other tissues but the rate of GNG never exceeds that of the liver. fatty acids: used for beta oxidation to provide acetyl coA to feed into TCA cycle. Regulation is highly coordinated by what? The purpose of GNG is to satisfy the plasma glucose levels for the tissues that require it for metabolism, this is mainly Red Blood Cells (RBCs): they cannot survive without glucose. It is coordinated by the ratios of glucagon and insulin. There are other hormone effects involved but glucagon and insulin are the main ones. Other hormones are especially important for short-term changes such as "fight or flight" or long term stress (cortisone). These hormones are all involved in regulation and share similar mechanisms. These hormones are mediators for mobilization of energy from fat tissue and protein tissue to drive gluconeogenesis. Glycolysis generates net 2 ATP but GNG consumes 6 ATP to generate 1 glucose from 2 pyruvate. Location wise glycolysis only occurs in the Location wise gluconeogenesis occurs in the mitochondria and cytosol, first step is in the mitochondria, pyruvate enters first inside it either turns it into PEP to be transported or turned into malate to get out. Only difference between pyruvate and alanine is Which 2 amino acids cannot be used for GNG? 18 can be, lysine and le Continue reading >>

Introduction To The Degradation And The Synthesis Of Glucose

Introduction To The Degradation And The Synthesis Of Glucose

Content: 1. Introduction to the degradation and the synthesis of glucose 2. Glycolysis 3. Gluconeogenesis _ Saccharides are one of the main nutrients for heterotrophic organisms. Saccharides can be found in each cell of the human body. Saccharides have many different functions: (1) source of energy, (2) source of carbon atoms for syntheses, (3) reserves of energy (glycogen), (4) structural function (proteoglycans). Glucose (Glc) is universal energetic substrate. One gram of glucose when oxidized provides 17 kJ (= 4 kcal). Of great importance is fact that our cells are capable of draining energy from glucose even in anaerobic conditions – this is not true for any other nutrient we use. There are some populations of cells that are strictly dependent on glucose – i.e. erythrocytes, cells of central nervous system, etc…. We would like to emphasize that pyruvate dehydrogenase reaction (PDH) is irreversible therefore it is not possible to synthesise glucose from fatty acids. Au contraire our cells are capable of converting excessive glucose into fatty acids and then into TAG. Glucose blood concentration is called glycemia. Glycemia is normally 3,3 – 5,6 mmol/l, glycemia can after a meal increase to 7,0 mmol/l. In physiological conditions glucose is not present in the urine. In case that glycemia is higher than 10,0 mmol/l the renal threshold is exceeded and glucose gets into the urine. This condition is called glycosuria. Thus when glycemia is higher than renal threshold (value of threshold is 10,0 mmol/l) glucose can be found in the urine. In the food is glucose in several forms: (1) free glucose, (2) part of oligosaccharides (predominantly disaccharides), and (3) part of polysaccharides. To the blood is from intestine released only free glucose. Sources of blood glu Continue reading >>

Glucose Can Be Synthesized From Noncarbohydrate Precursors - Biochemistry - Ncbi Bookshelf

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 >>

Fatty Acids -- Overview: Reaction Sum

Fatty Acids -- Overview: Reaction Sum

8 acetyl CoA + 7 ATP + 14 (NADPH + H+) -> palmitate (16:0) + 8 CoA + 7 (ADP + Pi) + 14 NADP+ +6 H2O This is the overall process for fatty acid synthesis. Acetyl CoA for fatty acid synthesis comes mostly from glycolytic breakdown of glucose. Glucose is first degraded to pyruvate by aerobic glycolysis in thecytoplasm. Pyruvate is then transported into the mitochondria, where pyruvate dehydrogenase oxidatively decarboxylates pyruvate, forming acetyl CoA and otherproducts. Acetyl CoA can then serve as a substrate for citratesynthesis. Citrate, in turn, can be transported out of the mitochondria to the cytoplasm (where fatty acid synthesis occurs), and there split to generate cytoplasmic acetyl CoA for fatty acid synthesis. Citrate can also be oxidized by the tricarboxylic acid cycle in the mitochondria to yield energy. Notice that the need first to form citrate, then to transport it to the cytoplasm and then split it in order to get acetyl CoA for fatty acid synthesis provides several points at which control over acetyl CoA availability can be exerted. Continue reading >>

Does Fat Convert To Glucose In The Body?

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 >>

More in ketosis