Mannoheptulose

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d-Mannoheptulose
Mannoheptulose.svg
Names
IUPAC name
d-Manno-hept-2-ulose
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.020.723 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C7H14O7/c8-1-3(10)5(12)7(14)6(13)4(11)2-9/h3,5-10,12-14H,1-2H2/t3-,5-,6-,7+/m1/s1 Yes check.svgY
    Key: HSNZZMHEPUFJNZ-QMTIVRBISA-N Yes check.svgY
  • InChI=1S/C7H14O7/c8-1-3(10)5(12)7(14)6(13)4(11)2-9/h3,5-10,12-14H,1-2H2/t3-,5-,6-,7+/m1/s1
  • O=C([C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO)CO
Properties
C7H14O7
Molar mass 210.182 g·mol−1
Density 1.7 g cm−3
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Mannoheptulose is a heptose, a monosaccharide with seven carbon atoms, and a ketose, with the characteristic carbonyl group of the carbohydrate present on a secondary carbon (functioning as a ketone group). The sugar alcohol form of mannoheptulose is known as perseitol. [1]

Contents

Inhibition of hexokinases

Mannoheptulose is a competitive and non-competitive inhibitor of both hexokinase and the related liver isozyme glucokinase. [2] [3] [4] By blocking the enzyme hexokinase, it prevents glucose phosphorylation, the first step in the fundamental biochemical pathway of glycolysis. As a result, the breakdown of glucose is inhibited.

Because of its inhibition of glycolysis in vitro , it has been investigated as a novel nutraceuticals for weight management for dogs. [5] [6] However, while mannoheptulose is suggested to affect the energy balance of adult dogs, independent of dosage and physical activity, research disagrees whether it significantly alters energy expenditure in dogs.

Inhibition of insulin secretion

Mannoheptulose has been reported to inhibit insulin secretion from pancreas. [7] This inhibition occurs because when mannoheptulose is present the glycolysis is inhibited (because there is no production of glucose-6-P) therefore no increase in ATP concentration which is required to close the KATP channel in the beta cells of the pancreas causing a diminution of calcium entry and insulin secretion.

Natural occurrence

Mannoheptulose is naturally occurring in alfalfa, [1] avocados, [8] [1] fig, [1] and the primrose. [1] Heptoses can make up over a tenth of the tissue dry weight of the avocado tree. [1] Though the carbohydrate is thought to be produced during photosynthesis [8] the precise biological pathway for the synthesis of mannoheptulose was unknown as of 2002. [1] Like other sugars it is transported in the phloem. [8] [1]

Related Research Articles

<span class="mw-page-title-main">Carbohydrate</span> Organic compound that consists only of carbon, hydrogen, and oxygen

A carbohydrate is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 and thus with the empirical formula Cm(H2O)n, which does not mean the H has covalent bonds with O. However, not all carbohydrates conform to this precise stoichiometric definition, nor are all chemicals that do conform to this definition automatically classified as carbohydrates.

<span class="mw-page-title-main">Glycolysis</span> Catabolic 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.

<span class="mw-page-title-main">Glucose</span> Naturally produced monosaccharide

Glucose is a sugar with the molecular formula C6H12O6. Glucose is overall 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.

<span class="mw-page-title-main">Insulin</span> Peptide hormone

Insulin is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the INS gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of glucose from the blood into liver, fat and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both. Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat.

<span class="mw-page-title-main">Phosphorylation</span> Chemical process of introducing a phosphate

In biochemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Protein phosphorylation often activates many enzymes.

<span class="mw-page-title-main">Hexokinase</span> Class of enzymes

A hexokinase is an enzyme that phosphorylates hexoses, forming hexose phosphate. In most organisms, glucose is the most important substrate for hexokinases, and glucose-6-phosphate is the most important product. Hexokinase possesses the ability to transfer an inorganic phosphate group from ATP to a substrate.

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.

<span class="mw-page-title-main">Glucagon</span> Peptide hormone

Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises the 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.

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

<span class="mw-page-title-main">Pyruvate kinase</span> Class of enzymes

Pyruvate kinase is the enzyme involved in the last step of glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), yielding one molecule of pyruvate and one molecule of ATP. Pyruvate kinase was inappropriately named before it was recognized that it did not directly catalyze phosphorylation of pyruvate, which does not occur under physiological conditions. Pyruvate kinase is present in four distinct, tissue-specific isozymes in animals, each consisting of particular kinetic properties necessary to accommodate the variations in metabolic requirements of diverse tissues.

<span class="mw-page-title-main">AMP-activated protein kinase</span> Class of enzymes

5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme that plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cellular energy is low. It belongs to a highly conserved eukaryotic protein family and its orthologues are SNF1 in yeast, and SnRK1 in plants. It consists of three proteins (subunits) that together make a functional enzyme, conserved from yeast to humans. It is expressed in a number of tissues, including the liver, brain, and skeletal muscle. In response to binding AMP and ADP, the net effect of AMPK activation is stimulation of hepatic fatty acid oxidation, ketogenesis, stimulation of skeletal muscle fatty acid oxidation and glucose uptake, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipogenesis, inhibition of adipocyte lipolysis, and modulation of insulin secretion by pancreatic β-cells.

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

In oncology, the Warburg effect is the observation that most cancer cells produce energy predominantly not through the 'usual' citric acid cycle and oxidative phosphorylation in the mitochondria as observed in normal cells, but through a less efficient process of 'aerobic glycolysis' consisting of a high level of glucose uptake and glycolysis followed by lactic acid fermentation taking place in the cytosol, not the mitochondria, even in the presence of abundant oxygen. This observation was first published by Otto Heinrich Warburg, who was awarded the 1931 Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme". The precise mechanism and therapeutic implications of the Warburg effect, however, remain unclear.

<span class="mw-page-title-main">Fructose 2,6-bisphosphate</span> Chemical compound

Fructose 2,6-bisphosphate, abbreviated Fru-2,6-P2, is a metabolite that allosterically affects the activity of the enzymes phosphofructokinase 1 (PFK-1) and fructose 1,6-bisphosphatase (FBPase-1) to regulate glycolysis and gluconeogenesis. Fru-2,6-P2 itself is synthesized and broken down by the bifunctional enzyme phosphofructokinase 2/fructose-2,6-bisphosphatase (PFK-2/FBPase-2).

Glucose-1,6-bisphosphate synthase is a type of enzyme called a phosphotransferase and is involved in mammalian starch and sucrose metabolism. It catalyzes the transfer of a phosphate group from 1,3-bisphosphoglycerate to glucose-1-phosphate, yielding 3-phosphoglycerate and glucose-1,6-bisphosphate.

<span class="mw-page-title-main">Enzyme activator</span> Molecules which increase enzyme activity

Enzyme activators are molecules that bind to enzymes and increase their activity. They are the opposite of enzyme inhibitors. These molecules are often involved in the allosteric regulation of enzymes in the control of metabolism. An example of an enzyme activator working in this way is fructose 2,6-bisphosphate, which activates phosphofructokinase 1 and increases the rate of glycolysis in response to the hormone glucagon. In some cases, when a substrate binds to one catalytic subunit of an enzyme, this can trigger an increase in the substrate affinity as well as catalytic activity in the enzyme's other subunits, and thus the substrate acts as an activator.

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.

<span class="mw-page-title-main">HK2</span>

Hexokinase 2 also known as HK2 is an enzyme which in humans is encoded by the HK2 gene on chromosome 2. Hexokinases phosphorylate glucose to produce glucose-6-phosphate (G6P), the first step in most glucose metabolism pathways. This gene encodes hexokinase 2, the predominant form found in skeletal muscle. It localizes to the outer membrane of mitochondria. Expression of this gene is insulin-responsive, and studies in rat suggest that it is involved in the increased rate of glycolysis seen in rapidly growing cancer cells. [provided by RefSeq, Apr 2009]

<span class="mw-page-title-main">HK3</span> Mammalian protein found in Homo sapiens

Hexokinase 3 also known as HK3 is an enzyme which in humans is encoded by the HK3 gene on chromosome 5. Hexokinases phosphorylate glucose to produce glucose-6-phosphate (G6P), the first step in most glucose metabolism pathways. This gene encodes hexokinase 3. Similar to hexokinases 1 and 2, this allosteric enzyme is inhibited by its product glucose-6-phosphate. [provided by RefSeq, Apr 2009]

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 Liu, Xuan; Sievert, James; Arpaia, Mary Lu; Madore, Monica A. (2002-01-01). "Postulated Physiological Roles of the Seven-carbon Sugars, Mannoheptulose, and Perseitol in Avocado". Journal of the American Society for Horticultural Science. 127 (1): 108–114. doi: 10.21273/JASHS.127.1.108 . Retrieved 2018-06-26.
  2. Sir Philip John Randle; Haldane "Hal" G. Coore (1 April 1964). "Inhibition of glucose phosphorylation by mannoheptulose". Biochemical Journal. 91 (1): 56–59. doi:10.1042/bj0910056. PMC   1202814 . PMID   5319361.
  3. Olivier Scruel; Chantal Vanhoutte; Abdullah Sener; Willy Jean Malaisse (1998-10-01). "Interference of D-mannoheptulose with D-glucose phosphorylation, metabolism and functional effects: Comparison between liver, parotid cells and pancreatic islets". Molecular and Cellular Biochemistry. 187 (1/2): 113–120. doi:10.1023/A:1006812300200. PMID   9788748. S2CID   28158640.
  4. Dai, N; Schaffer, A; Petreikov, M; Shahak, Y; Giller, Y; Ratner, K; Levine, A; Granot, D (1999). "Overexpression of Arabidopsis hexokinase in tomato plants inhibits growth, reduces photosynthesis, and induces rapid senescence". The Plant Cell. 11 (7): 1253–66. doi:10.1105/tpc.11.7.1253. PMC   144264 . PMID   10402427.
  5. McKnight, Leslie; Root-McCraig, Jared; Wright, David; Davenport, Gary; France, James; Shoveller, Anna Kate (2015). "Dietary Mannoheptulose Does Not Significantly Alter Daily Energy Expenditure in Adult Labrador Retrievers". PLOS ONE. 10 (12): e0143324. doi: 10.1371/journal.pone.0143324 . PMC   4684352 . PMID   26656105.
  6. McKnight, Leslie; Eyre, Ryan; Gooding, Margaret; Davenport, Gary; Shoveller, Anna Kate (2015). "Dietary Mannoheptulose Increases Fasting Serum Glucagon Like Peptide-1 and Post-Prandial Serum Ghrelin Concentrations in Adult Beagle Dogs". Animals. 5 (2): 442–454. doi: 10.3390/ani5020365 . PMC   4494402 . PMID   26479244.
  7. Lucke, Christoph; Kagan, Avir; Adelman, Neil; Glick, Seymour (1972). "Effect of 2-Deoxy-D-Glucose and Mannoheptulose on the Insulin Response to Amino Acids in Rabbits". Diabetes. 21 (1): 1–5. doi:10.2337/diab.21.1.1. PMID   5008084. S2CID   8357296.
  8. 1 2 3 Tesfay, Samson Zeray; Bertling, Isa; Bower, John P. (March 2012). Cowan, Ashton Keith (ed.). "D-mannoheptulose and perseitol in 'Hass' avocado: Metabolism in seed and mesocarp tissue". South African Journal of Botany. 79: 159–165. doi: 10.1016/j.sajb.2011.10.006 .