Carbohydrate metabolism

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Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation, breakdown, and interconversion of carbohydrates in living organisms.

Contents

Carbohydrates are central to many essential metabolic pathways. [1] Plants synthesize carbohydrates from carbon dioxide and water through photosynthesis, allowing them to store energy absorbed from sunlight internally. [2] When animals and fungi consume plants, they use cellular respiration to break down these stored carbohydrates to make energy available to cells. [2] Both animals and plants temporarily store the released energy in the form of high-energy molecules, such as ATP, for use in various cellular processes. [3]

Humans can consume a variety of carbohydrates, digestion breaks down complex carbohydrates into simple monomers (monosaccharides): glucose, fructose, mannose and galactose. After resorption in the gut, the monosaccharides are transported, through the portal vein, to the liver, where all non-glucose monosacharids (fructose, galactose) are transformed into glucose as well. [4] Glucose (blood sugar) is distributed to cells in the tissues, where it is broken down via cellular respiration, or stored as glycogen. [3] [4] In cellular (aerobic) respiration, glucose and oxygen are metabolized to release energy, with carbon dioxide and water as endproducts. [2] [4]

Metabolic pathways

Overview of connections between metabolic processes. Carbohydrate Metabolism.png
Overview of connections between metabolic processes.

Glycolysis

Glycolysis is the process of breaking down a glucose molecule into two pyruvate molecules, while storing energy released during this process as ATP and NADH. [2] Nearly all organisms that break down glucose utilize glycolysis. [2] Glucose regulation and product use are the primary categories in which these pathways differ between organisms. [2] In some tissues and organisms, glycolysis is the sole method of energy production. [2] This pathway is common to both anaerobic and aerobic respiration. [1]

Glycolysis consists of ten steps, split into two phases. [2] During the first phase, it requires the breakdown of two ATP molecules. [1] During the second phase, chemical energy from the intermediates is transferred into ATP and NADH. [2] The breakdown of one molecule of glucose results in two molecules of pyruvate, which can be further oxidized to access more energy in later processes. [1]

Glycolysis can be regulated at different steps of the process through feedback regulation. The step that is regulated the most is the third step. This regulation is to ensure that the body is not over-producing pyruvate molecules. The regulation also allows for the storage of glucose molecules into fatty acids. [5] There are various enzymes that are used throughout glycolysis. The enzymes upregulate, downregulate, and feedback regulate the process.

Gluconeogenesis

Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. [6] In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys. It is one of two primary mechanisms – the other being degradation of glycogen (glycogenolysis) – used by humans and many other animals to maintain blood sugar levels, avoiding low levels (hypoglycemia). [7] In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. [8] In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise.

In humans, substrates for gluconeogenesis may come from any non-carbohydrate sources that can be converted to pyruvate or intermediates of glycolysis (see figure). For the breakdown of proteins, these substrates include glucogenic amino acids (although not ketogenic amino acids); from breakdown of lipids (such as triglycerides), they include glycerol, odd-chain fatty acids (although not even-chain fatty acids, see below); and from other parts of metabolism they include lactate from the Cori cycle. Under conditions of prolonged fasting, acetone derived from ketone bodies can also serve as a substrate, providing a pathway from fatty acids to glucose. [9] Although most gluconeogenesis occurs in the liver, the relative contribution of gluconeogenesis by the kidney is increased in diabetes and prolonged fasting. [10]

The gluconeogenesis pathway 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. These ATPs are supplied from fatty acid catabolism via beta oxidation. [11]

Glycogenolysis

Glycogenolysis refers to the breakdown of glycogen. [12] In the liver, muscles, and the kidney, this process occurs to provide glucose when necessary. [12] A single glucose molecule is cleaved from a branch of glycogen, and is transformed into glucose-1-phosphate during this process. [1] This molecule can then be converted to glucose-6-phosphate, an intermediate in the glycolysis pathway. [1]

Glucose-6-phosphate can then progress through glycolysis. [1] Glycolysis only requires the input of one molecule of ATP when the glucose originates in glycogen. [1] Alternatively, glucose-6-phosphate can be converted back into glucose in the liver and the kidneys, allowing it to raise blood glucose levels if necessary. [2]

Glucagon in the liver stimulates glycogenolysis when the blood glucose is lowered, known as hypoglycemia. [12] The glycogen in the liver can function as a backup source of glucose between meals. [2] Liver glycogen mainly serves the central nervous system. Adrenaline stimulates the breakdown of glycogen in the skeletal muscle during exercise. [12] In the muscles, glycogen ensures a rapidly accessible energy source for movement. [2]

Glycogenesis

Glycogenesis refers to the process of synthesizing glycogen. [12] In humans, glucose can be converted to glycogen via this process. [2] Glycogen is a highly branched structure, consisting of the core protein Glycogenin, surrounded by branches of glucose units, linked together. [2] [12] The branching of glycogen increases its solubility, and allows for a higher number of glucose molecules to be accessible for breakdown at the same time. [2] Glycogenesis occurs primarily in the liver, skeletal muscles, and kidney. [2] The Glycogenesis pathway consumes energy, like most synthetic pathways, because an ATP and a UTP are consumed for each molecule of glucose introduced. [13]

Pentose phosphate pathway

The pentose phosphate pathway is an alternative method of oxidizing glucose. [12] It occurs in the liver, adipose tissue, adrenal cortex, testis, mammary glands, phagocytes, and red blood cells. [12] It produces products that are used in other cell processes, while reducing NADP to NADPH. [12] [14] This pathway is regulated through changes in the activity of glucose-6-phosphate dehydrogenase. [14]

Fructose metabolism

Fructose must undergo certain extra steps in order to enter the glycolysis pathway. [2] Enzymes located in certain tissues can add a phosphate group to fructose. [12] This phosphorylation creates fructose-6-phosphate, an intermediate in the glycolysis pathway that can be broken down directly in those tissues. [12] This pathway occurs in the muscles, adipose tissue, and kidney. [12] In the liver, enzymes produce fructose-1-phosphate, which enters the glycolysis pathway and is later cleaved into glyceraldehyde and dihydroxyacetone phosphate. [2]

Galactose metabolism

Lactose, or milk sugar, consists of one molecule of glucose and one molecule of galactose. [12] After separation from glucose, galactose travels to the liver for conversion to glucose. [12] Galactokinase uses one molecule of ATP to phosphorylate galactose. [2] The phosphorylated galactose is then converted to glucose-1-phosphate, and then eventually glucose-6-phosphate, which can be broken down in glycolysis. [2]

Energy production

Many steps of carbohydrate metabolism allow the cells to access energy and store it more transiently in ATP. [15] The cofactors NAD+ and FAD are sometimes reduced during this process to form NADH and FADH2, which drive the creation of ATP in other processes. [15] A molecule of NADH can produce 1.5–2.5 molecules of ATP, whereas a molecule of FADH2 yields 1.5 molecules of ATP. [16]

Energy produced during metabolism of one glucose molecule
PathwayATP inputATP outputNet ATPNADH outputFADH2 outputATP final yield
Glycolysis (aerobic)242205-7
Citric-acid cycle0228217-25

Typically, the complete breakdown of one molecule of glucose by aerobic respiration (i.e. involving both glycolysis and the citric-acid cycle) is usually about 30–32 molecules of ATP. [16] Oxidation of one gram of carbohydrate yields approximately 4 kcal of energy. [3]

Hormonal regulation

Glucoregulation is the maintenance of steady levels of glucose in the body.

Hormones released from the pancreas regulate the overall metabolism of glucose. [17] Insulin and glucagon are the primary hormones involved in maintaining a steady level of glucose in the blood, and the release of each is controlled by the amount of nutrients currently available. [17] The amount of insulin released in the blood and sensitivity of the cells to the insulin both determine the amount of glucose that cells break down. [4] Increased levels of glucagon activates the enzymes that catalyze glycogenolysis, and inhibits the enzymes that catalyze glycogenesis. [15] Conversely, glycogenesis is enhanced and glycogenolysis inhibited when there are high levels of insulin in the blood. [15]

The level of circulatory glucose (known informally as "blood sugar"), as well as the detection of nutrients in the Duodenum is the most important factor determining the amount of glucagon or insulin produced. The release of glucagon is precipitated by low levels of blood glucose, whereas high levels of blood glucose stimulates cells to produce insulin. Because the level of circulatory glucose is largely determined by the intake of dietary carbohydrates, diet controls major aspects of metabolism via insulin. [18] In humans, insulin is made by beta cells in the pancreas, fat is stored in adipose tissue cells, and glycogen is both stored and released as needed by liver cells. Regardless of insulin levels, no glucose is released to the blood from internal glycogen stores from muscle cells.

Carbohydrates as storage

Carbohydrates are typically stored as long polymers of glucose molecules with glycosidic bonds for structural support (e.g. chitin, cellulose) or for energy storage (e.g. glycogen, starch). However, the strong affinity of most carbohydrates for water makes storage of large quantities of carbohydrates inefficient due to the large molecular weight of the solvated water-carbohydrate complex. In most organisms, excess carbohydrates are regularly catabolised to form acetyl-CoA, which is a feed stock for the fatty acid synthesis pathway; fatty acids, triglycerides, and other lipids are commonly used for long-term energy storage. The hydrophobic character of lipids makes them a much more compact form of energy storage than hydrophilic carbohydrates. Gluconeogenesis permits glucose to be synthesized from various sources, including lipids. [19]

In some animals (such as termites [20] ) and some microorganisms (such as protists and bacteria), cellulose can be disassembled during digestion and absorbed as glucose. [21]

Human diseases

Related Research Articles

Glycolysis Metabolic pathway

Glycolysis is the metabolic pathway that converts glucose, into pyruvate. The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes. Capture of bond energy of carbohydrates. Storage of ATP

<span class="mw-page-title-main">Glucose</span> Simple form of sugar

Glucose is a simple sugar with the molecular formula C6H12O6. Glucose is the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using energy from sunlight, where it is used to make cellulose in cell walls, the most abundant carbohydrate in the world.

Phosphorylation Chemical process of introducing a phosphate

In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology. Protein phosphorylation often activates many enzymes.

<span class="mw-page-title-main">Cellular respiration</span> Process to convert glucose to ATP in cells

Cellular respiration is the process by which biological fuels are oxidised in the presence of an inorganic electron acceptor such as oxygen to produce large amounts of energy, to drive the bulk production of ATP. Cellular respiration may be described as a set of metabolic reactions and processes that take place in the cells of organisms to convert chemical energy from nutrients into adenosine triphosphate (ATP), and then release waste products.

Glycogen Glucose polymer used as energy store in animals

Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body.

Anabolism is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breaking-down aspect. Anabolism is usually synonymous with biosynthesis.

Gluconeogenesis Biological formation of glucose

Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys. It is one of two primary mechanisms – the other being degradation of glycogen (glycogenolysis) – used by humans and many other animals to maintain blood sugar levels, avoiding low levels (hypoglycemia). In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise.

Glucagon Peptide hormone

Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers extracellular glucose. It is produced from proglucagon, encoded by the GCG gene.

Fructose bisphosphatase deficiency Medical condition

In fructose bisphosphatase deficiency, there is not enough fructose bisphosphatase for gluconeogenesis to occur correctly. Glycolysis will still work, as it does not use this enzyme.

<span class="mw-page-title-main">Glycogenolysis</span>

Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase.

Phosphofructokinase 1 Class of enzymes

Phosphofructokinase-1 (PFK-1) is one of the most important regulatory enzymes of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors. PFK-1 catalyzes the important "committed" step of glycolysis, the conversion of fructose 6-phosphate and ATP to fructose 1,6-bisphosphate and ADP. Glycolysis is the foundation for respiration, both anaerobic and aerobic. Because phosphofructokinase (PFK) catalyzes the ATP-dependent phosphorylation to convert fructose-6-phosphate into fructose 1,6-bisphosphate and ADP, it is one of the key regulatory steps of glycolysis. PFK is able to regulate glycolysis through allosteric inhibition, and in this way, the cell can increase or decrease the rate of glycolysis in response to the cell's energy requirements. For example, a high ratio of ATP to ADP will inhibit PFK and glycolysis. The key difference between the regulation of PFK in eukaryotes and prokaryotes is that in eukaryotes PFK is activated by fructose 2,6-bisphosphate. The purpose of fructose 2,6-bisphosphate is to supersede ATP inhibition, thus allowing eukaryotes to have greater sensitivity to regulation by hormones like glucagon and insulin.

Glucose 6-phosphate Chemical compound

Glucose 6-phosphate is a glucose sugar phosphorylated at the hydroxy group on carbon 6. This dianion is very common in cells as the majority of glucose entering a cell will become phosphorylated in this way.

Glucokinase Enzyme participating to the regulation of carbohydrate metabolism

Glucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cells in the liver and pancreas of humans and most other vertebrates. In each of these organs it plays an important role in the regulation of carbohydrate metabolism by acting as a glucose sensor, triggering shifts in metabolism or cell function in response to rising or falling levels of glucose, such as occur after a meal or when fasting. Mutations of the gene for this enzyme can cause unusual forms of diabetes or hypoglycemia.

Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processes that generate energy and (2) anabolic processes where they serve as building blocks for other compounds.

Cori cycle Lactate degrading metabolic pathway

The Cori cycle, named after its discoverers, Carl Ferdinand Cori and Gerty Cori, is a metabolic pathway in which lactate, produced by anaerobic glycolysis in muscles, is transported to the liver and converted to glucose, which then returns to the muscles and is cyclically metabolized back to lactate.

Glycogen storage disease type I Medical condition

Glycogen storage disease type I is an inherited disease that results in the liver being unable to properly break down stored glycogen. This impairment disrupts the liver's ability to break down stored glycogen that is necessary to maintain adequate blood sugar levels. GSD I is divided into two main types, GSD Ia and GSD Ib, which differ in cause, presentation, and treatment. GSD Ia is caused by a deficiency in the enzyme glucose-6-phosphatase, while GSD Ib is caused a deficiency in the enzyme glucose-6-phosphate translocase. Since glycogenolysis is the principal metabolic mechanism by which the liver supplies glucose to the body during periods of fasting, both deficiencies cause severe low blood sugar and, over time, excess glycogen storage in the liver and the kidneys.

The glucose cycle occurs primarily in the liver and is the dynamic balance between glucose and glucose 6-phosphate. This is important for maintaining a constant concentration of glucose in the blood stream.

Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.

Fructolysis refers to the metabolism of fructose from dietary sources. Though the metabolism of glucose through glycolysis uses many of the same enzymes and intermediate structures as those in fructolysis, the two sugars have very different metabolic fates in human metabolism. Unlike glucose, which is directly metabolized widely in the body, fructose is almost entirely metabolized in the liver in humans, where it is directed toward replenishment of liver glycogen and triglyceride synthesis. Under one percent of ingested fructose is directly converted to plasma triglyceride. 29% - 54% of fructose is converted in liver to glucose, and about a quarter of fructose is converted to lactate. 15% - 18% is converted to glycogen. Glucose and lactate are then used normally as energy to fuel cells all over the body.

The insulin transduction pathway is a biochemical pathway by which insulin increases the uptake of glucose into fat and muscle cells and reduces the synthesis of glucose in the liver and hence is involved in maintaining glucose homeostasis. This pathway is also influenced by fed versus fasting states, stress levels, and a variety of other hormones.

References

  1. 1 2 3 4 5 6 7 8 Maughan, Ron (2009). "Carbohydrate metabolism". Surgery (Oxford). 27 (1): 6–10. doi:10.1016/j.mpsur.2008.12.002.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Nelson, David Lee (2013). Lehninger principles of biochemistry. Cox, Michael M., Lehninger, Albert L. (6th ed.). New York: W.H. Freeman and Company. ISBN   978-1429234146. OCLC   824794893.
  3. 1 2 3 Sanders, L. M. (2016). "Carbohydrate: Digestion, Absorption and Metabolism". Encyclopedia of Food and Health. pp. 643–650. doi:10.1016/b978-0-12-384947-2.00114-8. ISBN   9780123849533.
  4. 1 2 3 4 Hall, John E. (2015). Guyton and Hall Textbook of Medical Physiology E-Book (13 ed.). Elsevier Health Sciences. ISBN   978-0323389303.
  5. “Regulation of Cellular Respiration (Article).” Khan Academy. www.khanacademy.org, https://www.khanacademy.org/science/biology/cellular-respiration-and-fermentation/variations-on-cellular-respiration/a/regulation-of-cellular-respiration.
  6. Nelson DL, Cox MM (2000). Lehninger Principles of Biochemistry. USA: Worth Publishers. p.  724. ISBN   978-1-57259-153-0.
  7. Silva P. "The Chemical Logic Behind Gluconeogenesis". Archived from the original on August 26, 2009. Retrieved September 8, 2009.
  8. Beitz DC (2004). "Carbohydrate metabolism.". In Reese WO (ed.). Dukes' Physiology of Domestic Animals (12th ed.). Cornell Univ. Press. pp. 501–15. ISBN   978-0801442384.
  9. Kaleta C, de Figueiredo LF, Werner S, Guthke R, Ristow M, Schuster S (July 2011). "In silico evidence for gluconeogenesis from fatty acids in humans". PLOS Computational Biology. 7 (7): e1002116. Bibcode:2011PLSCB...7E2116K. doi:10.1371/journal.pcbi.1002116. PMC   3140964 . PMID   21814506.
  10. Swe MT, Pongchaidecha A, Chatsudthipong V, Chattipakorn N, Lungkaphin A (June 2019). "Molecular signaling mechanisms of renal gluconeogenesis in nondiabetic and diabetic conditions". Journal of Cellular Physiology. 234 (6): 8134–8151. doi:10.1002/jcp.27598. PMID   30370538. S2CID   53097552.
  11. Rodwell V (2015). Harper's illustrated Biochemistry, 30th edition. USA: McGraw Hill. p. 193. ISBN   978-0-07-182537-5.
  12. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Dashty, Monireh (2013). "A quick look at biochemistry: Carbohydrate metabolism". Clinical Biochemistry. 46 (15): 1339–52. doi:10.1016/j.clinbiochem.2013.04.027. PMID   23680095.
  13. Gropper, Sareen S.; Smith, Jack L.; Carr, Timothy P. (2016-10-05). Advanced Nutrition and Human Metabolism. Cengage Learning. ISBN   978-1-337-51421-7.
  14. 1 2 Ramos-Martinez, Juan Ignacio (2017-01-15). "The regulation of the pentose phosphate pathway: Remember Krebs". Archives of Biochemistry and Biophysics. 614: 50–52. doi:10.1016/j.abb.2016.12.012. ISSN   0003-9861. PMID   28041936.
  15. 1 2 3 4 Ahern, Kevin; Rajagopal, Indira; Tan, Taralyn (2017). Biochemistry Free for All. Oregon State University.
  16. 1 2 Energetics of Cellular Respiration (Glucose Metabolism).
  17. 1 2 Lebovitz, Harold E. (2016). "Hyperglycemia Secondary to Nondiabetic Conditions and Therapies". Endocrinology: Adult and Pediatric. pp. 737–51. doi:10.1016/b978-0-323-18907-1.00042-1. ISBN   9780323189071.
  18. Brockman, R P (March 1978). "Roles of glucagon and insulin in the regulation of metabolism in ruminants. A review". The Canadian Veterinary Journal. 19 (3): 55–62. ISSN   0008-5286. PMC   1789349 . PMID   647618.
  19. G Cooper, The Cell, American Society of Microbiology, p. 72
  20. Watanabe, Hirofumi; Hiroaki Noda; Gaku Tokuda; Nathan Lo (23 July 1998). "A cellulase gene of termite origin". Nature. 394 (6691): 330–31. Bibcode:1998Natur.394..330W. doi:10.1038/28527. PMID   9690469. S2CID   4384555.
  21. Coleman, Geoffrey (8 February 1978). "The Metabolism of Cellulose, Glucose, and Starch by the Rumen Ciliate Protozoon Eudiplodinium Magii". Journal of General Microbiology. 107 (2): 359–66. doi: 10.1099/00221287-107-2-359 .