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 >>
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) and fatty acid catabolism. Gluconeogenesis is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. 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. 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. In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs 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 >>
Can Amino Acids Be Used By The Body To Make Glucose & Fatty Acids?
Amino acids are nitrogen-containing molecules that are the building blocks of all proteins in food and in the body. They can be used as energy, yielding about 4 calories per gram, but their primary purpose is the synthesis and maintenance of body proteins including, but not limited to, muscle mass. Video of the Day During normal protein metabolism, a certain number of amino acids are pushed aside each day. When these amino acids are disproportionate to other amino acids for the synthesis of new protein, your liver and kidneys dispose of the nitrogen as urea, and the rest of the molecule is used as energy in a variety of ways. Then certain amino acids -- minus their nitrogen -- can enter the citric acid cycle -- the biochemical pathway that converts food into energy. Others can be converted to glucose or fat. This process may be enhanced when you take in more protein than you need. Your body relies on a continuous supply of glucose and fatty acids for energy for physical activity and cellular needs during rest. When you exercise, your body relies still more on glucose because fat is slower to metabolize. The higher your exercise intensity is, the more your body requires quicker-burning glucose. Some glucose is stored as glycogen in the liver and muscles and can be recruited when blood glucose is used up. When glycogen becomes depleted, the process of gluconeogenesis can take over -- the creation of new glucose from another source. The usual source for gluconeogenesis is amino acids. Healthy people store adequate body fat to cover their energy needs. Although certain amino acids can be converted to fatty acids, there should be no need for this to occur in order to supply energy. But if a very high protein intake adds substantially more calories, theoretically those extra 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 >>
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 >>
Metabolism: Transformations and Interactions Chemical Reactions in the Body Plants use the sunâ€™s energy to make carbohydrate from carbon dioxide and water. This is called photosynthesis. Humans and animals eat the plants and use the carbohydrate as fuel for their bodies. During digestion, the energy-yielding nutrients are broken down to monosaccharides, fatty acids, glycerol, and amino acids. After absorption, enzymes and coenzymes can build more complex compounds. In metabolism they are broken down further into energy (ATP), water and carbon dioxide. Chemical Reactions in the Body Metabolic reactions take place inside of cells, especially liver cells. Anabolism is the building up of body compounds and requires energy. Catabolism is the breakdown of body compounds and releases energy. Chemical Reactions in the Body Enzymes and coenzymes are helpers in reactions. Enzymes are protein catalysts that cause chemical reactions. Coenzymes are organic molecules that function as enzyme helpers. Cofactors are organic or inorganic substances that facilitate enzyme action. Breaking Down Nutrients for Energy The breakdown of glucose to energy starts with glycolysis to pyruvate. Pyruvate may be converted to lactic acid anaerobically (without oxygen) and acetyl CoA aerobically (with oxygen). Eventually, all energy-yielding nutrients enter the TCA cycle or tricarboxylic acid cycle (or Krebâ€™s cycle) and the electron transport chain. Breaking Down Nutrients for Energy Glucose Glucose-to-pyruvate is called glycolysis or glucose splitting. Pyruvateâ€™s Options Anaerobic â€“ lactic acid Aerobic â€“ acetyl CoA Pyruvate-to-Lactate Oxygen is not available or cells lack sufficient mitochondria Lactate is formed when hydrogen is added to pyruvate. Liver cells recycle 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 >>
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 >>
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 >>
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 >>
Sort What is the difference between energy and metabolism? Energy metabolism? Energy is the capacity to do work - heat, mechanical, electrical, CHEMICAL Metabolism is how the body uses food to meet its needs - specifically, it is the sum total of all chemical reactions in the living cells of the body - energy metabolism includes all reactions by which the body obtains and expends the energy from food What are the two types of metabolic reactions in the body? Anabolic/Anabolism - building body compounds (requires energy) - ex. glucose + glucose = glycogen - ex. glycerol + fatty acid = triglycerides - ex. amino acid + amino acid = protein Catabolic/Catabolism - breaking down body compounds (releases energy) - ex. glycogen -> glucose - ex. triglycerides -> glycerol + fatty acid - ex. protein -> amino acids What is ATP? How is it formed? (adenosine triphosphate) It is a molecule made up of three phosphate groups that has high energy bonds (so it provides lots of energy when it is broken down) - it is what provides energy for any reaction or cell activity in the body It is formed from the breakdown of glucose (glycolysis), fatty acids, and amino acids Its negative charge makes it vulnerable to hydrolysis What is the idea of coupled reactions? The body makes ATP in coupled reactions. Energy (ATP) is needed to facilitate the reactions that make more ATP. So the body uses ATP to make ATP 1.) ATP is broken down, which provides energy for a variety of functions in the body - when ATP is broken down, it loses a phosphate group and becomes ADP 2.) Energy is required to add a phosphate group to ADP to make ATP (uses ATP from food to do this) This system is about 50% efficient, and the rest is lost as heat How does digestion break things down into smaller units? Carbs -> glucose (and 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 >>
on on Fats (or triglycerides) within the body are ingested as food or synthesized by adipocytes or hepatocytes from carbohydrate precursors ([link]). 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 [link]b) 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 ([link]). The chylomicrons enable fats and cholesterol to move within the aqueous environment of your lymphatic and circulatory systems. Chylomicrons leave the enterocytes by exocytosis and enter the lymphatic system via lacteals in the villi of the intestine. From the lymphatic system, the chylo 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 >>