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Record Information
Version2.0
Creation Date2009-03-06 18:58:03 UTC
Update Date2014-12-24 20:21:05 UTC
Accession NumberT3D0091
Identification
Common NameChloride ion
ClassSmall Molecule
DescriptionIn nature, chlorine is most abundant as a chloride ion. Physiologically, it exists as an ion in the body. The chloride ion is an essential anion that the body needs for many critical functions. Chloride is a prominent negatively charged ion of the blood, where it represents 70% of the body’s total negative ion content. On average, an adult human body contains approximately 115 grams of chloride, making up about 0.15% of total body weight. The suggested amount of chloride intake ranges from 750 to 900 milligrams per day, based on the fact that total obligatory loss of chloride in the average person is close to 530 milligrams per day. Chloride helps keep the body's acid-base balance. The amount of chloride in the blood is carefully controlled by the kidneys. In addition to its functions as an electrolyte, chloride combines with hydrogen in the stomach to make hydrochloric acid, a powerful digestive enzyme that is responsible for the break down of proteins, absorption of other metallic minerals, and activation of intrinsic factor, which in turn absorbs vitamin B12. Chloride ions also have other important physiological roles. For instance, in the central nervous system, the inhibitory action of glycine and some of the action of GABA relies on the entry of Cl- into specific neurons. Also, the chloride-bicarbonate exchanger biological transport protein relies on the chloride ion to increase the blood's capacity of carbon dioxide, in the form of the bicarbonate ion. Chloride-transporting proteins (CLC) play fundamental roles in many tissues in the plasma membrane as well as in intracellular membranes. CLC proteins form a gene family that comprises nine members in mammals, at least four of which are involved in human genetic diseases. GABA(A) receptors are pentameric complexes that function as ligand-gated chloride ion channels. WNK kinases are a family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis, and they are found in diverse epithelia throughout the body that are involved in chloride ion flux. Cystic fibrosis (CF) is caused by alterations in the CF transmembrane conductance regulator (CFTCR) gene that result in deranged sodium and chloride ion transport channels. (1, 2, 3, 4, 6).
Compound Type
  • Halogen
  • Inorganic Compound
  • Natural Compound
Chemical Structure
Thumb
Synonyms
Synonym
Chloride
Chloride (1-)
Chlorine anion
Cl(-)
Cl(1-)
Chemical FormulaCl
Average Molecular Mass35.454 g/mol
Monoisotopic Mass34.969 g/mol
CAS Registry Number22537-115-1
IUPAC Namechloride
Traditional Namechloride
SMILES[Cl-]
InChI IdentifierInChI=1S/ClH/h1H/p-1
InChI KeyInChIKey=VEXZGXHMUGYJMC-UHFFFAOYSA-M
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as homogeneous halogens. These are inorganic non-metallic compounds in which the largest atom is a nobel gas.
KingdomInorganic compounds
Super ClassHomogeneous non-metal compounds
ClassHomogeneous halogens
Sub ClassNot Available
Direct ParentHomogeneous halogens
Alternative ParentsNot Available
Substituents
  • Homogeneous halogen
Molecular FrameworkNot Available
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • All Tissues
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid or Liquid
AppearanceClear liquid
Experimental Properties
PropertyValue
Melting PointDepends on salt form
Boiling PointDepends on salt form
Solubility>500 mg/mL at 25°C [AMOORE,JE & HAUTALA,E (1983)]
LogPNot Available
Predicted Properties
PropertyValueSource
logP0.61ChemAxon
pKa (Strongest Acidic)-7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity5.62 m3·mol-1ChemAxon
Polarizability2.39 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-9000000000-c4fb3d037fe2e74c2a5eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-9000000000-c4fb3d037fe2e74c2a5eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-9000000000-c4fb3d037fe2e74c2a5eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-9000000000-d488e6da5c7ecb77869aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-9000000000-d488e6da5c7ecb77869aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-9000000000-d488e6da5c7ecb77869aView in MoNA
Toxicity Profile
Route of ExposureInhalation (11) ; dermal (11)
Mechanism of ToxicityChloride imbalances can lead to electrolyte and pH imbalances. Excessive chloride in the blood is known as hyperchloremia. Often hyperchloremia is associated with excessive intakes of dietary chloride, which only occur with the ingestion of large amounts of salt and potassium chloride (hypernatremia). Hyperchloremia can also occur due to loss of body fluids from prolonged vomiting, sweating or fever, kidney failure, kidney disorders or diabetes. The amount of chloride in the blood is carefully controlled by the kidneys. Chloride toxicity has not been observed in humans except in the special case of impaired sodium chloride metabolism, e.g. in congestive heart failure.
MetabolismIn humans, 88% of chloride is extracellular and contributes to the osmotic activity of body fluids. The electrolyte balance in the body is maintained by adjusting total dietary intake and by excretion via the kidneys and gastrointestinal tract. Chloride is almost completely absorbed in normal individuals, mostly from the proximal half of the small intestine. Normal fluid loss amounts to about 1.5–2 litres/day, together with about 4 g of chloride per day. Most (90– 95%) is excreted in the urine, with minor amounts in faeces (4–8%) and sweat (2%). A normal adult human body contains approximately 81.7 g chloride. On the basis of a total obligatory loss of chloride of approximately 530 mg/day, a dietary intake for adults of 9 mg of chloride per kg of body weight has been recommended.
Toxicity ValuesNot Available
Lethal DoseEstimated fatal dose of sodium chloride and other chloride salts is approximately 0.75 to 3.00 g/kg
Carcinogenicity (IARC Classification)No indication of carcinogenicity (not listed by IARC). (12)
Uses/SourcesChloride is found in table salt as well as most foods. Chloride is an essential element or micronutrient and helps keep the body’s electrolyte balance.
Minimum Risk LevelNot Available
Health EffectsThe oral ingestion of larger quantities of sodium chloride, eg 1000 g in 600 mL of water, is harmful and can induce irritation of the gastrointestinal tract, vomiting, hypernatremia, respiratory distress, convulsions, and death. Hyperchloremia can also occur due to loss of body fluids from prolonged vomiting, sweating or fever, kidney failure, kidney disorders or diabetes. Hyperchloremia is associated with deep and labored breathing, weakness, and intense thirst. Cystic fibrosis (CF) is caused by alterations in the CF transmembrane conductance regulator (CFTCR) gene that result in deranged sodium and chloride ion transport channels. This leads to the production of very salty sweat and the excessive production of mucous in the lungs. More than 100 genetic diseases or inborn errors of metabolism are associated with electrolyte (i.e. chloride) imbalances.
SymptomsHyperchloremia can be symptomatic with signs of deep and labored breathing (often associated with severe metabolic acidosis, particularly diabetic ketoacidosis (DKA) but also renal failure), weakness, and intense thirst.
TreatmentAs with most types of electrolyte imbalance, the treatment of high blood chloride levels is based on correcting the underlying cause. If the patient is dehydrated, therapy consists of establishing and maintaining adequate hydration. If the condition is caused or exacerbated by medications or treatments, these may be altered or discontinued, if deemed prudent. If there is underlying kidney disease (which is likely if there are other electrolyte disturbances), then the patient will be referred to a nephrologist for further care. If there is an underlying dysfunction of the endocrine or hormone system, the patient will likely be referred to an endocrinologist for further assessment.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB00492
PubChem Compound ID24526
ChEMBL IDNot Available
ChemSpider ID4514529
KEGG IDC00115
UniProt IDNot Available
OMIM ID103600 , 106195 , 109270 , 109280 , 111000 , 111300 , 118425 , 118930 , 121011 , 123885 , 125950 , 126650 , 131399 , 137163 , 137165 , 137192 , 138491 , 139392 , 141850 , 141900 , 145260 , 145500 , 160800 , 160900 , 166600 , 167050 , 171050 , 171060 , 173393 , 179800 , 181750 , 182307 , 186854 , 188070 , 192320 , 214700 , 218000 , 219700 , 223900 , 229100 , 230000 , 236200 , 241200 , 244400 , 248250 , 250900 , 255700 , 259700 , 261600 , 263800 , 264350 , 270420 , 277180 , 300008 , 300009 , 300138 , 300398 , 300554 , 302910 , 305990 , 308990 , 310468 , 560000 , 600041 , 600170 , 600228 , 600229 , 600232 , 600233 , 600359 , 600421 , 600436 , 600570 , 600580 , 600637 , 600760 , 600761 , 600791 , 600839 , 600840 , 600968 , 600997 , 601199 , 601271 , 601330 , 601678 , 601690 , 601844 , 601881 , 602023 , 602024 , 602056 , 602158 , 602359 , 602421 , 602522 , 602668 , 602722 , 602726 , 602727 , 602872 , 602958 , 602974 , 603080 , 603339 , 603353 , 603475 , 603506 , 603743 , 603831 , 603855 , 603906 , 604003 , 604045 , 604119 , 604159 , 604309 , 604337 , 604433 , 604471 , 604708 , 604878 , 604879 , 604943 , 604996 , 605125 , 605208 , 605232 , 605377 , 605646 , 605784 , 606038 , 606205 , 606410 , 606412 , 606465 , 606516 , 606520 , 606533 , 606536 , 606672 , 606680 , 606718 , 606726 , 606757 , 606845 , 606904 , 606983 , 607096 , 607239 , 607293 , 607335 , 607364 , 607582 , 607589 , 607591 , 607628 , 607631 , 607682 , 607854 , 608041 , 608390 , 608479 , 608480 , 608481 , 608855 , 608893 , 608919 , 609448 , 609914 , 610130 , 610291 , 610791 , 611316 , 611490 , 611492
ChEBI ID29310
BioCyc IDCPD-4521
CTD IDD002713
Stitch IDChlorine
PDB IDCL
ACToR ID275
Wikipedia LinkChlorine
References
Synthesis ReferenceWeber, Rainer; Bulan, Andreas; Haas, Michel; Warsitz, Rafael; Werner, Knud. Production of chlorine from hydrogen chloride and oxygen. PCT Int. Appl. (2007), 30pp. CODEN: PIXXD2 WO 2007134861 A1 20071129 CAN 148:35931 AN 2007:1361621
MSDSLink
General References
  1. Harrison NL: Mechanisms of sleep induction by GABA(A) receptor agonists. J Clin Psychiatry. 2007;68 Suppl 5:6-12. [17539703 ]
  2. Zifarelli G, Pusch M: CLC chloride channels and transporters: a biophysical and physiological perspective. Rev Physiol Biochem Pharmacol. 2007;158:23-76. [17729441 ]
  3. Tarran R, Donaldson S, Boucher RC: Rationale for hypertonic saline therapy for cystic fibrosis lung disease. Semin Respir Crit Care Med. 2007 Jun;28(3):295-302. [17562499 ]
  4. Kahle KT, Wilson FH, Lalioti M, Toka H, Qin H, Lifton RP: WNK kinases: molecular regulators of integrated epithelial ion transport. Curr Opin Nephrol Hypertens. 2004 Sep;13(5):557-62. [15300163 ]
  5. Fainsinger RL: Palliative care in Edmonton. Support Care Cancer. 1995 Mar;3(2):91-2. [7539703 ]
  6. Evans RB: Chlorine: state of the art. Lung. 2005 May-Jun;183(3):151-67. [16078037 ]
  7. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  8. Dart, R.C. (ed). Medical Toxicology. Third Edition, Lippincott Williams & Wilkins. Philadelphia, PA. 2004, p. 1058
  9. ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for chlorine. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  10. Wikipedia. Chlorine. Last Updated 25 July 2009. [Link]
  11. International Programme on Chemical Safety (IPCS) INCHEM (2008). Poison Information Monograph for Chlorine. [Link]
  12. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Transporter activity
Specific Function:
Chloride/bicarbonate exchanger. Mediates the efficient absorption of chloride ions in the colon, participating in fluid homeostasis. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation.
Gene Name:
SLC26A3
Uniprot ID:
P40879
Molecular Weight:
84504.035 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Chloride channel activity
Specific Function:
Seems to act as a chloride ion channel.
Gene Name:
CLCC1
Uniprot ID:
Q96S66
Molecular Weight:
62021.97 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Voltage-gated chloride channel activity
Specific Function:
Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport.
Gene Name:
CLCN1
Uniprot ID:
P35523
Molecular Weight:
108625.435 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Voltage-gated chloride channel activity
Specific Function:
Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport.
Gene Name:
CLCN2
Uniprot ID:
P51788
Molecular Weight:
98534.425 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Voltage-gated chloride channel activity
Specific Function:
Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. May be important in urinary concentrating mechanisms.
Gene Name:
CLCNKA
Uniprot ID:
P51800
Molecular Weight:
75284.08 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Voltage-gated chloride channel activity
Specific Function:
Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. May be important in urinary concentrating mechanisms.
Gene Name:
CLCNKB
Uniprot ID:
P51801
Molecular Weight:
75445.3 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Voltage-gated ion channel activity
Specific Function:
Can insert into membranes and form chloride ion channels. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Involved in regulation of the cell cycle.
Gene Name:
CLIC1
Uniprot ID:
O00299
Molecular Weight:
26922.47 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Voltage-gated ion channel activity
Specific Function:
Can insert into membranes and form chloride ion channels. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Modulates the activity of RYR2 and inhibits calcium influx.
Gene Name:
CLIC2
Uniprot ID:
O15247
Molecular Weight:
28356.1 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Voltage-gated ion channel activity
Specific Function:
Required for normal hearing (PubMed:24781754). It is necessary for the formation of stereocilia in the inner ear and normal development of the organ of Corti (By similarity). Can insert into membranes and form poorly selective ion channels that may also transport chloride ions. May play a role in the regulation of transepithelial ion absorption and secretion. Is required for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture (PubMed:15184393, PubMed:18028448, PubMed:20335315).
Gene Name:
CLIC5
Uniprot ID:
Q9NZA1
Molecular Weight:
46502.195 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Pdz domain binding
Specific Function:
Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO1. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation.
Gene Name:
CFTR
Uniprot ID:
P13569
Molecular Weight:
168139.895 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Voltage-gated chloride channel activity
Specific Function:
Slowly voltage-gated channel mediating the exchange of chloride ions against protons. Functions as antiporter and contributes to the acidification of the lysosome lumen.
Gene Name:
CLCN7
Uniprot ID:
P51798
Molecular Weight:
88678.26 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Neurotransmitter:sodium symporter activity
Specific Function:
Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A1
Uniprot ID:
P30531
Molecular Weight:
67073.0 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Neurotransmitter:sodium symporter activity
Specific Function:
Required for the uptake of creatine in muscles and brain.
Gene Name:
SLC6A8
Uniprot ID:
P48029
Molecular Weight:
70522.17 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Neurotransmitter:sodium symporter activity
Specific Function:
Terminates the action of glycine by its high affinity sodium-dependent reuptake into presynaptic terminals. May be responsible for the termination of neurotransmission at strychnine-sensitive glycinergic synapses.
Gene Name:
SLC6A5
Uniprot ID:
Q9Y345
Molecular Weight:
87433.13 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Taurine:sodium symporter activity
Specific Function:
Sodium-dependent taurine and beta-alanine transporter. Chloride ions are necessary for optimal uptake.
Gene Name:
SLC6A6
Uniprot ID:
P31641
Molecular Weight:
69829.405 Da
References
  1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. [11917096 ]
General Function:
Temperature-gated cation channel activity
Specific Function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular Weight:
127499.88 Da
References
  1. Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]