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 >>
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 >>
Biochemistry - Why Isn't Acetyl-coa An Entry Point For Gluconeogenesis? - Biology Stack Exchange
Why isn't acetyl-coA an entry point for gluconeogenesis? The process of gluconeogenesis starts from various possible precursors - plausible entry points like, Pyruvate, OAA, Fumarate, Propionate (as succinate) and alpha-KG. It is important to note that, acetyl-coA is not an entry point for Gluconeogenesis. The most common reason cited for this is the irreversibility of the enzyme, pyruvate dehydrogenase. Since it is irreversible, Acetyl coA can't get back to pyruvate to go on forming glucose. But, Acetyl CoA naturally enters the Kreb's cycle, so why can't it go ahead and form glucose via gluconeogenesis using one of the Kreb's intermediates? I have had this doubt for very long and tried to come up with an explanation to satisfy myself but I still don't know if it is valid. So here it goes. All the entry points to gluconeogenesis (mentioned before) are an addition to the Kreb's cycle. They get on the boat, sail along, get off at oxaloacetate and leave. They don't bother the boat in any other way. Even Pyruvate, forms oxaloacetate via pyruvate carboxylase and then gets on the boat for gluconeogenesis. On the other hand, Acetyl coA would be a part of the Kreb's cycle itself. It is not adding anything to it (2 carbons that are added are lost as CO2). So an Acetyl CoA added, can't leave as OAA. It would be analogous not sailing on the boat but eating it down itself. Slowly, it would lead to a decay and loss of the intermediates Kreb's cycle and it would come to a standstill (?) Is this explanation right? Are there any other ways to explain why irreversibility of PDH results in this? Although acetyl-coA can enter gluconeogenesis via pathways like glyoxylate cycle (not in humans) and pathways to make pyruvate from acetone (not economical) to form glucose, the question is why Continue reading >>
Gluconeogenesis Flashcards | Quizlet
What is the definition of gluconeogensis? the synthesis of glucose from noncarbohydrate precursors how many days do the direct glucose reserves sufficient for the needs of the body? how many grams of glucose does the brain need daily? how many grams of glucose does the entire body need daily? how many grams of glucose are in body fluids to use for the body? how mans grams of readily mobilized glucose are there in glycogen stores? What is the major site of gluconeogenesis? mostly by the liver, and a smaller amount in the kidney 1. decreased insulin/glucagon ratio as in an overnight fast 3. high protein-low carb diet (need minimum of 50 g carb for insulin secretion) 4. stress; due to the hormones cortisol and epinephrine which are elevated under these conditions What are the 4 major non-carbohydrate presursors used as substrates for gluconeogenesis? 2. amino acids (muscle protein degradation in skeletal muscle) 3. glycerol (triglyceride breakdown in adipose tissue) what is lactate's role in the gluconeogenic pathway? 1. during vigorous exercise, lactate buildup and NADH 2. NADH can be reoxidized during the reduction of pyruvate to lactate 3. lactate is then returned to the liver, where it can be reoxidized to pyruvate by liver LDH the liver provides glucose to muscle for exercise and then reprocesses lactate into new glucose in the liver, what is the reaction when lactate enters from the blood? Lactate + LDH -> pyruvate + 6 phosphoryl groups -> glucose to the muscle what compound does muscle protein degradation give to gluconeogenesis? what is the process of alanine for conversion to glucose? alanine + alanine aminotransferase -> pyruvate what compound does triglyceride breakdown in adipose tissue give to gluconeogenesis? what is the process of glycerol for conversion to Continue reading >>
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 >>
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 >>
Biochemistry 11: Regulation And Integration
These are notes from lecture 11 of Harvard Extension’s biochemistry class. metabolic profiles of organs The liver: carbohydrates. The liver acts as a blood glucose buffer, takes up and releases glucose into the blood via GLUT2. G6P in the liver has three fates: glycogen production, glycolysis or the pentose phosphate pathway. The liver creates glucose from glycogen breakdown and gluconeogenesis. lipids. When fuel supplies are ample, the liver synthesizes fatty acids. It releases fatty acids it has synthesized or that have been liberated from adipose tissue as VLDLs. During starvation, it converts fatty acids to ketone bodies. amino acids. The liver absorbs most of the dietary amino acids. It can either synthesize proteins or catabolize amino acids depending on metabolic needs. It runs the urea cycle when needed to remove nitrogen. The brain: Very active respiratory metabolism: ~20% of the body’s total oxygen consumption and ~60% of our daily intake of glucose, used primarily to maintain the Na+ / K+ gradient across neuronal membranes. The brain cannot store glycogen. It also cannot use fatty acids as fuels, since albumin can’t cross the blood brain barrier. It can switch to ketone bodies when necessary to minimize protein degradation. Muscle: Can use fatty acids, glucose, and ketone bodies as fuel. It has large glycogen stores but uses them solely for itself, never exports (it lacks glucose 6 phosphatase unlike the liver). Muscle can be divided into resting, moderately active and active. Resting muscle mostly uses fatty acids as fuel. Moderately active muscle uses glucose from glycogen as well as fatty acids. Active muscle runs glycolysis at a rate exceeding the rate of the CAC, resulting in lactate buildup. Lactate is later converted back to glucose in the Cori C Continue reading >>
Gluconeogenesis - Kansas State Hn 400 Human Nutrition
Gluconeogenesis: The opposite of glycolysis, using other products like amino acids to make glucose. Amino acid uptake go from the amino acids through the amino acid transporters into the hepatocyte. The anabolic pathway of amino acids leads to protein synthesis. The catabolic pathway of amino acids can lead to gluconeogenesis that assist the formation of glucose. As shown below gluconeogenesis is like glycolysis in reverse with an oxaloacetate workaround. Oxaloacetate is a TCA cycle intermediate that is formed instead of directly converting pyruvate to phosphoenolpyruvate, which would be glycolysis exactly in reverse. Oxaloacetate then is just what is formed as an intermediate between the two steps. This gluconeogenesis animation does a good job of illustrating and explaining gluconeogenesis. We can use amino acids in gluconeogenesis to make glucose, but we cannot use ALL amino acids. Fatty acids cannot be used to form glucose because it makes Acetyl-CoA. The transition reaction that forms acetyl CoA from pyruvate is a one way reaction. This means that Acetyl-CoA can't be used to form pyruvate. In othe words, we can not go back from Acetyl-CoA to pyruvate. This occurs in the liver & kidney to some extent. Glucose is exported to tissues. Pyruvate is decarboxylated - the carboxyl group (-COOH) is split forming carbon dioxide. It is dehydrogenated - elimination of hydrogren It is added to CoA to form Acetyl CoA - remember CoA is Coenzyme A, responsible for oxidizing pyruvate in the Citric Acid/Kreb's cycle Why can't Acetyl CoA be used to from glucose through the Kreb's cycle? Because the Acetyl CoA carbons are given off as CO2, there is no carbon skeleton left to be used for gluconeogenesis. Glycerol can be used, but it makes very little glucose. Shows where all the amino Continue reading >>
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 >>
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 >>
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 >>
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 >>
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 >>
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 >>