Carboxyatractyloside

Last updated
Carboxyatractyloside
Carboxyatractyloside.svg
Names
IUPAC name
15α-Hydroxy-2β-[2-O-(3-methylbutanoyl)-3,4-di-O-sulfono-β-D-glucopyranosyloxy]-5β,8α,9β,10α,13α-kaur-16-ene-18,19-dioic acid
Systematic IUPAC name
(2S,4aS,6aR,7S,9R,11aS,11bS)-7-Hydroxy-2-({(2R,3R,4R,5R,6R)-6-(hydroxymethyl)-3-[(3-methylbutanoyl)oxy]oxan-2-yl}oxy)-11b-methyl-8-methylidenedodecahydro-6a,9-methanocyclohepta[a]naphthalene-4,4(1H)-dicarboxylic acid
Other names
CATR
Identifiers
3D model (JSmol)
ChemSpider
DrugBank
EC Number
  • 251-444-9
PubChem CID
UNII
  • InChI=1S/C31H46O18S2/c1-14(2)9-21(33)47-24-23(49-51(42,43)44)22(48-50(39,40)41)18(13-32)46-26(24)45-17-11-29(4)19-6-5-16-10-30(19,25(34)15(16)3)8-7-20(29)31(12-17,27(35)36)28(37)38/h14,16-20,22-26,32,34H,3,5-13H2,1-2,4H3,(H,35,36)(H,37,38)(H,39,40,41)(H,42,43,44)/t16-,17+,18-,19+,20+,22-,23+,24-,25+,26-,29+,30-/m1/s1
    Key: AQFATIOBERWBDY-LNQSNDDKSA-N
  • CC(CC(=O)O[C@H]1[C@@H](O[C@@H]([C@H]([C@@H]1OS(=O)(=O)O)OS(=O)(=O)O)CO)O[C@@H]2C[C@@]([C@@H]3[C@@](C2)([C@H]4[C@@]5([C@H](C(=C)[C@@H](C5)CC4)O)CC3)C)(C(=O)O)C(=O)O)C
Properties
C31H46O18S2
Molar mass 770.81 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Carboxyatractyloside (CATR) is a highly toxic diterpene glycoside that inhibits the ADP/ATP translocase. It is about 10 times more potent than its analog atractyloside. [1] While atractyloside is effective in the inhibition of oxidative phosphorylation, carboxyatractyloside is considered to be more effective. [2] The effects of carboxyatractyloside on the ADP/ATP translocase are not reversed by increasing the concentration of adenine nucleotides, unlike its counterpart atractyloside. [2] Carboxyatractyloside behavior resembles bongkrekic acid while in the mitochondria. [2] Carboxyatractyloside is poisonous to humans as well as livestock, including cows [3] and horses. [4]

Symptoms of carboxyatractyloside poisoning may include abdominal pain, nausea and vomiting, drowsiness, palpitations, sweating and trouble breathing. [5] In severe cases, convulsions, liver failure and loss of consciousness may develop, which can lead to death. [5]

Carboxyatractyloside can be found in Xanthium species plants, including Xanthium strumarium . [6] Consumption of Xanthium containing the toxin led to the deaths of at least 19 people in Sylhet, Bangladesh during a period of food scarcity. [7] Along with atractyloside, it is also one of the main poisonous substances in the Atractylis gummifera thistle. [8]

Related Research Articles

<span class="mw-page-title-main">Adenosine triphosphate</span> Energy-carrying molecule in living cells

Adenosine triphosphate (ATP) is a nucleotide that provides energy to drive and support many processes in living cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known forms of life, it is often referred to as the "molecular unit of currency" of intracellular energy transfer.

<span class="mw-page-title-main">Oxidative phosphorylation</span> Metabolic pathway

Oxidative phosphorylation or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine triphosphate (ATP). In eukaryotes, this takes place inside mitochondria. Almost all aerobic organisms carry out oxidative phosphorylation. This pathway is so pervasive because it releases more energy than alternative fermentation processes such as anaerobic glycolysis.

<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 oxidized in the presence of an inorganic electron acceptor, such as oxygen, to drive the bulk production of adenosine triphosphate (ATP), which contains energy. 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 ATP, and then release waste products.

<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.

<i>Xanthium</i> Genus of plants

Xanthium (cocklebur) is a genus of flowering plants in the tribe Heliantheae within the family Asteraceae, native to the Americas and eastern Asia and some parts of south Asia.

<span class="mw-page-title-main">Mitochondrial matrix</span> Space within the inner membrane of the mitochondrion

In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions.[1] The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate, and the beta oxidation of fatty acids.

Substrate-level phosphorylation is a metabolism reaction that results in the production of ATP or GTP supported by the energy released from another high-energy bond that leads to phosphorylation of ADP or GDP to ATP or GTP (note that the reaction catalyzed by creatine kinase is not considered as "substrate-level phosphorylation"). This process uses some of the released chemical energy, the Gibbs free energy, to transfer a phosphoryl (PO3) group to ADP or GDP. Occurs in glycolysis and in the citric acid cycle.

<span class="mw-page-title-main">Inner mitochondrial membrane</span>

The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space.

<span class="mw-page-title-main">Bongkrek acid</span> Chemical compound

Bongkrek acid is a respiratory toxin produced in fermented coconut or corn contaminated by the bacterium Burkholderia gladioli pathovar cocovenenans. It is a highly toxic, heat-stable, colorless, odorless, and highly unsaturated tricarboxylic acid that inhibits the ADP/ATP translocase, also called the mitochondrial ADP/ATP carrier, preventing ATP from leaving the mitochondria to provide metabolic energy to the rest of the cell. Bongkrek acid, when consumed through contaminated foods, mainly targets the liver, brain, and kidneys along with symptoms that include vomiting, diarrhea, urinary retention, abdominal pain, and excessive sweating. Most of the outbreaks are found in Indonesia and China where fermented coconut and corn-based foods are consumed.

<span class="mw-page-title-main">Oligomycin</span> Group of chemical compounds

Oligomycins are macrolides created by Streptomyces that are strong antibacterial agents but are often poisonous to other organisms, including humans.

<span class="mw-page-title-main">Mitochondrial membrane transport protein</span>

Mitochondrial membrane transport proteins, also known as mitochondrial carrier proteins, are proteins which exist in the membranes of mitochondria. They serve to transport molecules and other factors, such as ions, into or out of the organelles. Mitochondria contain both an inner and outer membrane, separated by the inter-membrane space, or inner boundary membrane. The outer membrane is porous, whereas the inner membrane restricts the movement of all molecules. The two membranes also vary in membrane potential and pH. These factors play a role in the function of mitochondrial membrane transport proteins. There are 53 discovered human mitochondrial membrane transporters, with many others that are known to still need discovered.

<i>Xanthium strumarium</i> Species of flowering plant

Xanthium strumarium is a species of annual plants of the family Asteraceae. Some sources claim it originates in southern Europe and Asia, but has been extensively naturalized elsewhere. Others, such as the Flora of China and Flora of North America, state it originates in the Americas but was an early introduction to Eurasia.

<span class="mw-page-title-main">Adenine nucleotide translocator</span> Class of transport proteins

Adenine nucleotide translocator (ANT), also known as the ADP/ATP translocase (ANT), ADP/ATP carrier protein (AAC) or mitochondrial ADP/ATP carrier, exchanges free ATP with free ADP across the inner mitochondrial membrane. ANT is the most abundant protein in the inner mitochondrial membrane and belongs to mitochondrial carrier family.

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

Mitochondrial carriers are proteins from solute carrier family 25 which transfer molecules across the membranes of the mitochondria. Mitochondrial carriers are also classified in the Transporter Classification Database. The Mitochondrial Carrier (MC) Superfamily has been expanded to include both the original Mitochondrial Carrier (MC) family and the Mitochondrial Inner/Outer Membrane Fusion (MMF) family.

Translocase is a general term for a protein that assists in moving another molecule, usually across a cell membrane. These enzymes catalyze the movement of ions or molecules across membranes or their separation within membranes. The reaction is designated as a transfer from “side 1” to “side 2” because the designations “in” and “out”, which had previously been used, can be ambiguous. Translocases are the most common secretion system in Gram positive bacteria.

<span class="mw-page-title-main">ADP/ATP translocase 4</span> Protein-coding gene in the species Homo sapiens

ADP/ATP translocase 4 (ANT4) is an enzyme that in humans is encoded by the SLC25A31 gene on chromosome 4. This enzyme inhibits apoptosis by catalyzing ADP/ATP exchange across the mitochondrial membranes and regulating membrane potential. In particular, ANT4 is essential to spermatogenesis, as it imports ATP into sperm mitochondria to support their development and survival. Outside this role, the SLC25AC31 gene has not been implicated in any human disease.

<span class="mw-page-title-main">ADP/ATP translocase 3</span> Protein-coding gene in humans

ADP/ATP translocase 3, also known as solute carrier family 25 member 6, is a protein that in humans is encoded by the SLC25A6 gene.

<span class="mw-page-title-main">ADP/ATP translocase 2</span> Protein-coding gene in humans

ADP/ATP translocase 2 is a protein that in humans is encoded by the SLC25A5 gene on the X chromosome.

<span class="mw-page-title-main">Atractyloside</span> Chemical compound

Atractyloside (ATR) is a natural, toxic glycoside present in numerous plant species worldwide in the daisy family including Atractylis gummifera and Callilepis laureola, and it's used for a variety of therapeutic, religious, and toxic purposes. Exposure to ATR via ingestion or physical contact is toxic and can be fatal for both humans and animals, especially by kidney and liver failure. ATR acts as an effective ADP/ATP translocase inhibitor which eventually halts ADP and ATP exchange and the cell dies due to lack of energy. Historically, atractyloside poisoning has been challenging to verify and quantify toxicologically, though recent literature has described such methods within acceptable standards of forensic science.

<i>Chamaeleon gummifer</i> Species of plant in Asteraceae family

Chamaeleon gummifer, also known as distaff thistle or stemless atractylis, is a thistle in the Chamaeleon genus. Formerly, it was placed in the Atractylis genus. It is native to the Mediterranean basin, where it can be found in various habitats, including cultivated- or uncultivated fields and forests. It is a perennial herb producing a stemless, pinkish flower. The plant has a history of use in folk medicine, but it is very toxic due to the presence of atractyloside and carboxyatractyloside.

References

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  2. 1 2 3 Luciani S, Martini N, Santi R (September 1971). "Effects of carboxyatractyloside a structural analogue of atractyloside on mitochondrial oxidative phosphorylation". Life Sciences. 10 (17, Pt. 2): 961–8. doi:10.1016/0024-3205(71)90099-3. PMID   4255019.
  3. Botha CJ, Lessing D, Rösemann M, van Wilpe E, Williams JH (September 2014). "Analytical confirmation of Xanthium strumarium poisoning in cattle". J Vet Diagn Invest. 26 (5): 640–645. doi: 10.1177/1040638714542867 . hdl: 2263/42413 . PMID   25012081.
  4. Wilson, DA (2011). "Cocklebur Toxicosis". Clinical Veterinary Advisor - The Horse. University of Missouri, Columbia, Missouri: Elsevier. p. 115-116. ISBN   978-1-4160-9979-6.
  5. 1 2 Turgut M, Alhan CC, Gürgöze M, Kurt A, Doğan Y, Tekatli M, et al. (June 2005). "Carboxyatractyloside poisoning in humans". Annals of Tropical Medicine and Public Health. 25 (2): 125–134. doi:10.1179/146532805X45728. PMID   15949201. S2CID   25371968 . Retrieved 1 January 2021.
  6. Plumlee, Konnie (2004). "Chapter 25 - Plants". Clinical Veterinary Toxicology. Mosby. ISBN   978-0-323-01125-9.
  7. Gurley ES, Rahman M, Hossain MJ, Nahar N, Faiz MA, Islam N, et al. (March 2010). "Fatal outbreak from consuming Xanthium strumarium seedlings during time of food scarcity in northeastern Bangladesh". PLOS ONE. 5 (3): e9756. Bibcode:2010PLoSO...5.9756G. doi: 10.1371/journal.pone.0009756 . PMC   2841199 . PMID   20305785.
  8. Daniele C, Dahamna S, Firuzi O, Sekfali N, Saso L, Mazzanti G (February 2005). "Atractylis gummifera L. poisoning: an ethnopharmacological review". Ethnopharmacol. 97 (3): 175–181. doi:10.1016/j.jep.2004.11.025. PMID   15707749.