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 >>
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 >>
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 >>
Fat-to-glucose Interconversion By Hydrodynamic Transfer Of Two Glyoxylate Cycle Enzyme Genes
Fat-to-glucose interconversion by hydrodynamic transfer of two glyoxylate cycle enzyme genes 1Department of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra, Pamplona, Spain 2Laboratory of Animal Physiology and Nutrition, School of Agronomy, Public University of Navarra, Pamplona, Spain Received 2008 Sep 29; Accepted 2008 Dec 10. Copyright 2008 Cordero et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The glyoxylate cycle, which is well characterized in higher plants and some microorganisms but not in vertebrates, is able to bypass the citric acid cycle to achieve fat-to-carbohydrate interconversion. In this context, the hydrodynamic transfer of two glyoxylate cycle enzymes, such as isocytrate lyase (ICL) and malate synthase (MS), could accomplish the shift of using fat for the synthesis of glucose. Therefore, 20 mice weighing 23.37 0.96 g were hydrodinamically gene transferred by administering into the tail vein a bolus with ICL and MS. After 36 hours, body weight, plasma glucose, respiratory quotient and energy expenditure were measured. The respiratory quotient was increased by gene transfer, which suggests that a higher carbohydrate/lipid ratio is oxidized in such animals. This application could help, if adequate protocols are designed, to induce fat utilization for glucose synthesis, which might be eventually useful to reduce body fat depots in situations of obesity and diabetes. Thousands of different life-related biochemical processes, such as cell respiration and many other metabolic reactions, can lead to the producti Continue reading >>
Pathways In The Coordination Of Cellular Glucose And Fat Metabolism
Pathways in the coordination of cellular glucose and fat metabolism Last Updated on Sat, 04 Mar 2017 | Fatty Acids The metabolism of fat and carbohydrate are closely linked; optimal oxidation of fat and conservation of glucose occur in the fed state and the opposite in the fasted state. Current theory identifies two major biochemical pathways as central components of this integrated coordination of energy metabolism . These are the glucose-fatty acid cycle first described in 1963 (Randle et al., 1963) and the malonyl CoA / carnitine palmitoyl transferase (CPT)-1 pathway which was suggested by the studies of McGarry and coworkers in the late 1970s (McGarry et al., 1977). Importantly, these two pathways complement each other (Fig. 2.1). The glucose- fatty acid cycle links carbohydrate and fat metabolism and was one of the first theories to describe how fatty acids influence glucose metabolism . It centres on the proposition that increased beta-oxidation (utilisation) of fatty acids in skeletal muscle results in a reduced uptake and oxidation of glucose (Fig. 2.1), offering additional fine-tuning to the 'coarse' control of glucose and fat utilisation that is enforced at whole body level, by insulin (Frayn, 2003). Although recent advances in the study of whole body glucose metabolism in humans using nuclear magnetic resonance (NMR) spectroscopy, have challenged details of the glucose fatty acid cycle theory, they do confirm that fatty acids can antagonise glucose metabolism and insulin action at cellular level (Shulman, 2000). Fig. 2.1 Schematic diagram representing the fatty acid/glucose cycle and the malonyl CoA/CPT-1 system involved in coordination of glucose and lipid metabolism. The malonyl CoA/CPT-1 pathway operates in a reverse manner to the glucose fatty acid cycle Continue reading >>
Gluconeogenesis - An Overview | Sciencedirect Topics
Gluconeogenesis is the process that leads to the generation of glucose from a variety of sources such as pyruvate, lactate, glycerol, and certain amino acids. Larry R. Engelking, in Textbook of Veterinary Physiological Chemistry (Third Edition) , 2015 Gluconeogenesis occurs in the liver and kidneys. Gluconeogenesis supplies the needs for plasma glucose between meals. Gluconeogenesis is stimulated by the diabetogenic hormones (glucagon, growth hormone, epinephrine, and cortisol). Gluconeogenic substrates include glycerol, lactate, propionate, and certain amino acids. PEP carboxykinase catalyzes the rate-limiting reaction in gluconeogenesis. The dicarboxylic acid shuttle moves hydrocarbons from pyruvate to PEP in gluconeogenesis. Gluconeogenesis is a continual process in carnivores and ruminant animals, therefore they have little need to store glycogen in their liver cells. Of the amino acids transported to liver from muscle during exercise and starvation, Ala predominates. b-Aminoisobutyrate, generated from pyrimidine degradation, is a (minor) gluconeogenic substrate. N.V. Bhagavan, Chung-Eun Ha, in Essentials of Medical Biochemistry , 2011 Gluconeogenesis refers to synthesis of new glucose from noncarbohydrate precursors, provides glucose when dietary intake is insufficient or absent. It also is essential in the regulation of acid-base balance, amino acid metabolism, and synthesis of carbohydrate derived structural components. Gluconeogenesis occurs in liver and kidneys. The precursors of gluconeogenesis are lactate, glycerol, amino acids, and with propionate making a minor contribution. The gluconeogenesis pathway consumes ATP, which is derived primarily from the oxidation of fatty acids. The pathway uses several enzymes of the glycolysis with the exception of enzymes Continue reading >>
Connections Of Carbohydrate, Protein, And Lipid Metabolic Pathways
Connecting Other Sugars to Glucose Metabolism Sugars, such as galactose, fructose, and glycogen, are catabolized into new products in order to enter the glycolytic pathway. Learning Objectives Identify the types of sugars involved in glucose metabolism Key Takeaways When blood sugar levels drop, glycogen is broken down into glucose -1-phosphate, which is then converted to glucose-6-phosphate and enters glycolysis for ATP production. In the liver, galactose is converted to glucose-6-phosphate in order to enter the glycolytic pathway. Fructose is converted into glycogen in the liver and then follows the same pathway as glycogen to enter glycolysis. Sucrose is broken down into glucose and fructose; glucose enters the pathway directly while fructose is converted to glycogen. disaccharide: A sugar, such as sucrose, maltose, or lactose, consisting of two monosaccharides combined together. glycogen: A polysaccharide that is the main form of carbohydrate storage in animals; converted to glucose as needed. monosaccharide: A simple sugar such as glucose, fructose, or deoxyribose that has a single ring. You have learned about the catabolism of glucose, which provides energy to living cells. But living things consume more than glucose for food. How does a turkey sandwich end up as ATP in your cells? This happens because all of the catabolic pathways for carbohydrates, proteins, and lipids eventually connect into glycolysis and the citric acid cycle pathways. Metabolic pathways should be thought of as porous; that is, substances enter from other pathways, and intermediates leave for other pathways. These pathways are not closed systems. Many of the substrates, intermediates, and products in a particular pathway are reactants in other pathways. Like sugars and amino acids, the catabo Continue reading >>
There are three groups of molecules that form the core building blocks and fuel substrates in the body: carbohydrates (glucose and other sugars); proteins and their constituent amino acids; and lipids and their constituent fatty acids. The biochemical processes that allow these molecules to be synthesized and stored (anabolism) or broken down to generate energy (catabolism) are referred to as metabolic pathways. Glucose metabolism involves the anabolic pathways of gluconeogenesis and glycogenesis, and the catabolic pathways of glycogenolysis and glycolysis. Lipid metabolism involves the anabolic pathways of fatty acid synthesis and lipogenesis and the catabolic pathways of lipolysis and fatty acid oxidation. Protein metabolism involves the anabolic pathways of amino acid synthesis and protein synthesis and the catabolic pathways of proteolysis and amino acid oxidation. Under conditions when glucose levels inside the cell are low (such as fasting, sustained exercise, starvation or diabetes), lipid and protein catabolism includes the synthesis (ketogenesis) and utilization (ketolysis) of ketone bodies. The end products of glycolysis, fatty acid oxidation, amino acid oxidation and ketone body degradation can be oxidised to carbon dioxide and water via the sequential actions of the tricarboxylic acid cycle and oxidative phosphorylation, generating many molecules of the high energy substrate adenosine triphosphate (ATP). Interplay between metabolic pathways The interplay between glucose metabolism, lipid metabolism, ketone body metabolism and protein and amino acid metabolism is summarized in Figure 1. Amino acids can be a source of glucose synthesis as well as energy production and excess glucose that is not required for energy production can be stored as glycogen or metabo Continue reading >>
The Catabolism Of Fats And Proteins For Energy
Before we get into anything, what does the word catabolism mean? When we went over catabolic and anabolic reactions, we said that catabolic reactions are the ones that break apart molecules. To remember what catabolic means, think of a CATastrophe where things are falling apart and breaking apart. You could also remember cats that tear apart your furniture. In order to make ATP for energy, the body breaks down mostly carbs, some fats and very small amounts of protein. Carbs are the go-to food, the favorite food that cells use to make ATP but now we’re going to see how our cells use fats and proteins for energy. What we’re going to find is that they are ALL going to be turned into sugars (acetyl) as this picture below shows. First let’s do a quick review of things you already know because it is assumed you learned cell respiration already and how glucose levels are regulated in your blood! Glucose can be stored as glycogen through a process known as glycogenesis. The hormone that promotes this process is insulin. Then when glycogen needs to be broken down, the hormone glucagon, promotes glycogenolysis (Glycogen-o-lysis) to break apart the glycogen and increase the blood sugar level. Glucose breaks down to form phosphoglycerate (PGAL) and then pyruvic acid. What do we call this process of splitting glucose into two pyruvic sugars? That’s glycolysis (glyco=glucose, and -lysis is to break down). When there’s not enough oxygen, pyruvic acid is converted into lactic acid. When oxygen becomes available, lactic acid is converted back to pyruvic acid. Remember that this all occurs in the cytoplasm. The pyruvates are then, aerobically, broken apart in the mitochondria into Acetyl-CoA. The acetyl sugars are put into the Krebs citric acid cycle and they are totally broken 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 >>
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 >>
164 24.3 Lipid Metabolism
Learning Objectives By the end of this section, you will be able to: Explain how energy can be derived from fat Explain the purpose and process of ketogenesis Describe the process of ketone body oxidation Explain the purpose and the process of lipogenesis Fats (or triglycerides) within the body are ingested as food or synthesized by adipocytes or hepatocytes from carbohydrate precursors (Figure 1). Lipid metabolism entails the oxidation of fatty acids to either generate energy or synthesize new lipids from smaller constituent molecules. Lipid metabolism is associated with carbohydrate metabolism, as products of glucose (such as acetyl CoA) can be converted into lipids. Lipid metabolism begins in the intestine where ingested triglycerides are broken down into smaller chain fatty acids and subsequently into monoglyceride molecules (see Figure 1b) by pancreatic lipases, enzymes that break down fats after they are emulsified by bile salts. When food reaches the small intestine in the form of chyme, a digestive hormone called cholecystokinin (CCK) is released by intestinal cells in the intestinal mucosa. CCK stimulates the release of pancreatic lipase from the pancreas and stimulates the contraction of the gallbladder to release stored bile salts into the intestine. CCK also travels to the brain, where it can act as a hunger suppressant. Together, the pancreatic lipases and bile salts break down triglycerides into free fatty acids. These fatty acids can be transported across the intestinal membrane. However, once they cross the membrane, they are recombined to again form triglyceride molecules. Within the intestinal cells, these triglycerides are packaged along with cholesterol molecules in phospholipid vesicles called chylomicrons (Figure 2). The chylomicrons enable fats an 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 >>
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 | 8 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 >>
The Science Behind Fat Metabolism
Per the usual disclaimer, always consult with your doctor before experimenting with your diet (seriously, go see a doctor, get data from blood tests, etc.). Please feel free to comment below if you’re aware of anything that should be updated; I’d appreciate knowing and I’ll update the content quickly. My goal here is to help a scientifically curious audience know the basic story and where to dive in for further study. If I’m successful, the pros will say “duh”, and everyone else will be better informed about how this all works. [UPDATE: based on a ton a helpful feedback and questions on the content below, I’ve written up a separate article summarizing the science behind ketogenic (low-carb) diets. Check it out. Also, the below content has been updated and is still very much applicable to fat metabolism on various kinds of diets. Thanks, everyone!] tl;dr The concentration of glucose in your blood is the critical upstream switch that places your body into a “fat-storing” or “fat-burning” state. The metabolic efficiency of either state — and the time it takes to get into one from the other — depends on a large variety of factors such as food and drink volume and composition, vitamin and mineral balances, stress, hydration, liver and pancreas function, insulin sensitivity, exercise, mental health, and sleep. Carbohydrates you eat, with the exception of indigestible forms like most fibers, eventually become glucose in your blood. Assuming your metabolism is functioning normally, if the switch is on you will store fat. If the switch is off, you will burn fat. Therefore, all things being equal, “diets” are just ways of hacking your body into a sufficiently low-glycemic state to trigger the release of a variety of hormones that, in turn, result in Continue reading >>