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 >>
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Glucogenic Amino Acids
DOUGLAS C. HEIMBURGER MD, in Handbook of Clinical Nutrition (Fourth Edition) , 2006 The major aim of protein catabolism during a state of starvation is to provide the glucogenic amino acids (especially alanine and glutamine) that serve as substrates for endogenous glucose production (gluconeogenesis) in the liver. In the hypometabolic/starved state, protein breakdown for gluconeogenesis is minimized, especially as ketones become the substrate preferred by certain tissues. In the hypermetabolic/stress state, gluconeogenesis increases dramatically and in proportion to the degree of the insult to increase the supply of glucose (the major fuel of reparation). Glucose is the only fuel that can be utilized by hypoxic tissues (anaerobic glycolysis), by phagocytosing (bacteria-killing) white cells, and by young fibroblasts. Infusions of glucose partially offset a negative energy balance but do not significantly suppress the high rates of gluconeogenesis in the catabolic patient. Hence, adequate supplies of protein are needed to replace the amino acids utilized for this metabolic response. In summary, the two physiologic states represent different responses to starvation. The hypometabolic patient, who conserves body mass by reducing the metabolic rate and using fat as the primary fuel (rather than glucose and its precursor amino acids), is adapted to starvation. The hypermetabolic patient also uses fat as a fuel but rapidly breaks down body protein to produce glucose, the fuel of reparation, thereby causing loss of muscle and organ tissue and endangering vital body functions. Joerg Klepper*, in Handbook of Clinical Neurology , 2013 Gluconeogenesis, predominantly in the liver, generates glucose from noncarbohydrate substrates such as lactate, glycerol, and glucogenic amino acid Continue reading >>
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: 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 >>
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Glucogenic Amino Acid
Paulo Ricardo Nazrio Viecili*12, ... Jonatas Z. Klafke*3, in Advances in Clinical Chemistry , 2017 TGs are lipid molecules formed by glycerol derived from carbon hydrates and/or gluconeogenic amino acids, bound to three FAs. These FAs have a similar conformation in most TG molecules: there is a saturated FA in position 1, an unsaturated FA in position 2, and a long-chain FA in position 3 (see Fig. 1) [1]. TGs are the most abundant lipids in nature, and their main characteristic is their essentially nonpolar nature, since the polar regions of their precursors (glycerol hydroxyls and carboxyls of the FAs) vanish when the ester bonds are formed. Animal fats and vegetable oils are complexes formed by TGs, the difference between them being the specific FAs that compose them. TGs in animal fats are predominantly composed of saturated FAs, lending them their solid appearance, while unsaturated FAs predominate in vegetable oils, giving them their liquid consistency. Both animal fats and vegetable oils can be digested in the organism thanks to hydrolysis by lipases [15]. TGs are synthesized through two main pathways: the glycerol phosphate pathway and the monoacylglycerol (MAG) pathway. The glycerol phosphate pathway is more common and is present in various cell types. This pathway is based on the acylation of glycerol 3-phosphate through the addition of FA groups, each of which is catalyzed by a different enzyme. In contrast, the MAG pathway predominates in the small intestine and generates TGs based on MAG derived from dietary fat. The glycerol phosphate pathway occurs as follows: first, acylation of glycerol 3-phosphate (addition of FA) occurs by the glycerol 3-phosphate acyltransferase, which is present in the endoplasmic reticulum and mitochondria, forming lysophosphatidic 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 >>
Amino Acid Metabolism!
Our current examination of proteins and amino acids will cover the metabolism of the protein we eat, dietary protein, and catabolic situations in the body. Amino acids are the "building-blocks" of proteins. Proteins, from the Greek word meaning "of prime importance," constitute an array of structures. Examples of these structures include hormones, enzymes, and muscle tissue. The primary function of protein is growth and repair of body tissue (anabolism). Proteins can also be used as energy through catabolic (breakdown of tissues) reactions, such as gluconeogenesis-the process of making glucose from amino acids, lactate, glycerol, or pyruvate in the liver or kidneys. Our current examination of proteins and amino acids will cover the metabolism of the protein we eat, dietary protein, and catabolic situations in the body. A general understanding of the molecular structure of proteins and amino acids is needed to understand their metabolism. Protein is comprised of carbon, hydrogen, oxygen and, most importantly, nitrogen. Protein may also contain sulfur, cobalt, iron, and phosphorus. These elements form the "building blocks" of protein, amino acids . A protein molecule is made up of long chains of amino acids bonded to each other by amide bonds, or peptide linkages. The food (protein) we eat contains different amino acids depending on the type of amino acids present. An almost endless combination of amino acid bonds can exist. The combination of amino acids governs the protein's properties. Just as the combination of amino acids governs the specific proteins properties, the structure of individual amino acids determines its function in the body. An amino acid is made up of a central carbon atom, a positively charged amine group (NH2) at one end and a negatively charged car 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 >>
Glucogenic And Ketogenic Amino Acids
Amino acids can be classified as being “glucogenic” or “ketogenic” based on the type of intermediates that are formed during their breakdown or catabolism. The catabolism of glucogenic amino acids produces either pyruvate or one of the intermediates in the Krebs Cycle. The catabolism of ketogenic amino acids produces acetyl CoA or acetoacetyl CoA (see Figure 1). There is a rare medical condition in which a person is deficient in the pyruvate dehydrogenase enzyme that converts pyruvate to acetyl CoA – a precursor for the Krebs Cycle. Signs and symptoms vary, but there are generally two main manifestations. First, patients can have an elevated blood lactate (lactic acid) level. Second, patients may have neurological defects, including microcephaly (a small head circumference) and/or mental retardation. Treatment is currently limited and not very effective. Moreover, damage to the brain is often irreversible. Your biochemistry study partner looks at Figure 1 and exclaims, “This doesn’t make sense - why can’t acetyl-coA and the ketogenic amino acids be converted back to pyruvate to create glucose using pyruvate dehydrogenase?” With your knowledge of basic chemistry, you answer: Continue reading >>
Ketogenic Amino Acid
All mammals synthesize saturated fatty and monounsaturated fatty acids de novo from simple precursors such as glucose or ketogenic amino acids. However, mammals cannot insert double bonds more proximal to the methyl end than the ninth carbon atom. Thus, two fatty acids having their first double bonds at the 6th and 3rd carbon atoms, namely, linoleic (18:2 n-6) and alpha-linolenic acid (18:3 n-3), respectively, cannot be synthesized de novo. Therefore, these fatty acids have to be supplied through the diet and are called essential fatty acids. Denoting the position of the first double bond proximal to the methyl end of the fatty acid chain, essential fatty acids are also classified as omega-6 (n-6) and omega-3 (n-3) fatty acids. A list of the most common n-3 and n-6 fatty acids and their systemic, common name, and shorthand notation is shown in Table 28.1. As early as the1930s, the essentiality of linoleic acid (18:2 n-6) and alpha-linolenic acid (18:3 n-3) in rat diets was identified (Burr and Burr, 1930). However, the essentiality of n-3 fatty acids in humans was first demonstrated only in the early 1980s (Holman et al., 1982). M. Saleet Jafri*, Rashmi Kumar, in Progress in Molecular Biology and Translational Science , 2014 One of the primary functions of the mitochondria is catabolic energy metabolism; that is, substrates, such as carbohydrates, fatty acids, and proteins, are broken down to release energy that is stored in high-energy phosphate bonds in molecules such as ATP and CP (creatine phosphate). This occurs in multiple stages by multiple pathways. (1) The tricarboxylic acid (TCA) cycle breaks down small carbohydrates (acetyl-CoA and TCA cycle intermediates) to produce reducing equivalents, that store the released energy. (2) There are also pathways that bring Continue reading >>
Can The Human Body Turn Excess Glucose Into Proteins?
Answered Apr 19, 2016 Author has 8.4k answers and 5.9m answer views No. Glucose is absorbed into our living cells via insulin for instant energy and any excess energy will be first stored in our liver and muscle glycogen then once your glycogen storages are full, they will be converted into fatty acids. Glucose is hydrocarbon chain while amino acids have nitride in the backbone. You can't create nitride out of nowhere. Answered Dec 26, 2017 Author has 1.5k answers and 370.1k answer views Yes. Glucose is the starting point for the synthesis of the nonessential amino acids, which are then incorporated into proteins. A simple pathway to illustrate the point is glucose pyruvate alanine. The last step involves transamination, so you need glucose plus nitrogen from the bodys nitrogen pool. Excess glucose can not be directly converted into protein as it is converted into glycogen and beyond its storage of glycogen in liver and muscles cells into fats. But glucose involved in metabolic pathway indirectly contribute to protein formation. Proteins are made up of amino acids. Amino acids has amino group and a carbon skeleton. During amino acid synthesis amino group for most of amino acid is derived from glutamate but carbon skeletons are derived from commonly available metabolic intermediates of glycolysis, the citric acid cycle, or the pentosr phosphate pathway. The primary carbon sources are glycerate-3-phosphate, pyruvate, PEP , alpha ketoglutarate, oxaloacetate, ribose-5-phosphate, phosphoenolpyruvate and erythrose-4-phosphate. Most of body usable carbohydrates are converted to glucose and glucose undergo glycolysis followed by TCA or Pentose phosphate pathway and above mentioned products are formed during that. The body does to some extent indirectly convert glucose into pro Continue reading >>
Protein Will Not Make You Fat
Here's what you need to know... While it's biochemically possible for protein to turn into fat by ingesting extremely high numbers of calories or extremely large amounts of protein, it's unlikely you'll ever be in that situation. You can pretty much eat as much protein as you want and it won't turn to fat. That old chestnut about only being able to absorb 30 grams of protein in one sitting is bunk. Aside from building muscle, protein provides essential amino acids that serve as the building blocks for other proteins, enzymes, and hormones within the body that are vital for normal functioning. Without this steady supply of amino acids, the body resorts to breaking down its own proteins – typically from muscle – in order to meet this demand. Protein has its share of misconceptions. It's not uncommon to hear claims that dietary protein eaten in excess of some arbitrary number will be stored as body fat. Even those who are supposed to be reputable sources for nutrition information propagate this untenable dogma. While paging through a nutrition textbook I came across a section in the protein chapter regarding amino acids and energy metabolism (1). To quote the book directly: "Eating extra protein during times of glucose and energy sufficiency generally contributes to more fat storage, not muscle growth. This is because, during times of glucose and energy excess, your body redirects the flow of amino acids away from gluconeogenesis and ATP-producing pathways and instead converts them to lipids. The resulting lipids can subsequently be stored as body fat for later use." This is, more or less, supported by another textbook I own (2): "In times of excess energy and protein intakes coupled with adequate carbohydrate intake, the carbon skeleton of amino acids may be used to s 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 >>
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Amino Acid Metabolism
Amino acids assimilated by your body cells face two possible fates. One of them is protein synthesis, either directly, in the form in which they have been assimilated into the cell, or after being restructured by transamination to specific other (non-essential) amino acids , needed by the cell to assemble particular proteins. The other fate is amino acid degradation, i.e. splitting amino group from the carbon skeleton, with the amino group either disposed of through the urea cycle, or used for nucleotide synthesis, and carbon skeleton converted to metabolites feeding catabolic energy producing pathways - glycolysis and Krebs cycle. Most proteins are synthesized in millions of tiny structures made around ribosomal RNA (rRNA) molecules, called ribosomes. Free ribosomes are scattered throughout cytosol (intercellular fluid filling the space between outer cell membrane and cellular organelles), while membrane-bound ribosomes are attached to the cytosolic side of the endoplasmic reticulum (ER) membrane. Ribosomes bind to the messenger RNA (mRNA), carrying protein codes taken from DNA strands in the nucleus, and synthesize corresponding protein molecules of amino acids present in the cytosol (synthesis of all amino acids is initiated in the cytosol, with significant portion of them - mainly glycoproteins - being completed in the ER) and brought to them by the transfer RNA (tRNA) molecules. These amino acids feed anabolic pathways, that are creating unimaginable volume of protein molecules. An average cell uses some 10,000 to 20,000 different proteins, and contains about Where each protein molecule goes during and after synthesis is determined by its specific chemical "tag", making it subject to some form of cellular transport. Completed proteins are usually transferred to th Continue reading >>
Why Can Fatty Acids Not Be Converted Into Glucose? : Mcat
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