Record Information
Version1.0
Created at2020-03-18 23:22:03 UTC
Updated at2020-12-07 19:06:56 UTC
CannabisDB IDCDB006159
Secondary Accession NumbersNot Available
Cannabis Compound Identification
Common NameCitric acid
DescriptionCitric acid (citrate) is a weak tricarboxylic acid that is formed in the tricarboxylic acid cycle. In humans citric acid is produced endogenously or it may be introduced with diet, with citrus fruits being a key source. Citrate is produced by all aerobic organisms, from microbes to humans. Citrate is formed in the TCA cycle via the enzyme known as citrate synthase, which catalyzes the condensation of oxaloacetate with acetyl CoA to form citrate. Citrate then acts as the substrate for aconitase and is converted into aconitic acid. Some bacteria (notably E. coli) can produce and consume citrate internally as part of their TCA cycle, but are unable to use it as food because they lack the enzymes required to import it into the cell. Citrate has a number of biological roles in humans. In particular, it can be transported out of the mitochondria and into the cytoplasm, then broken down into acetyl-CoA for fatty acid synthesis. Citrate can also acts as a signalling molecule. High concentrations of cytosolic citrate can inhibit phosphofructokinase, the catalyst of a rate-limiting step of glycolysis. Inhibition of glycolysis has been shown to suppress tumor growth in a number of animal models ( PMID: 28674429 ). Citrate is also a vital component of bone, helping to regulate the size of apatite crystals. Urinary citrate levels can be used to identify a number of disorders. Indeed urinary citrate excretion is a common tool in the differential diagnosis of kidney stones, renal tubular acidosis and it plays also a role in characterizing bone diseases such as osteoporosis (PMID 12957820 ). The secretory epithelial cells of the prostate gland of humans and other animals possess a unique citrate-related metabolic pathway regulated by testosterone and prolactin. This specialized hormone-regulated metabolic activity is responsible for the major prostate function of the production and secretion of extraordinarily high levels of citrate. The key regulatory enzymes directly associated with citrate production in the prostate cells are mitochondrial aspartate aminotransferase, pyruvate dehydrogenase, and mitochondrial aconitase. Testosterone and prolactin are involved in the regulation of the corresponding genes associated with these enzymes (PMID 12198595 ). In addition to its biological roles and endogenous production, citrate is obtained from many other sources and used in many applications. Citric acid is found in citrus fruits, most concentrated in lemons and limes, where it can comprise as much as 8% of the dry weight of the fruit. The concentrations of citric acid in citrus fruits range from 5 mM for oranges and grapefruits to 300 mM in lemons and limes. However, these values vary within species depending upon the cultivar and the circumstances in which the fruit was grown. Citric acid is a natural preservative and is also used to add an acidic (sour) taste to foods and soft drinks. Citric acid is used as an excipient in pharmaceutical preparations due to its antioxidant properties. It can be used to treat water, which makes it useful in improving the effectiveness of soaps and laundry detergents. Citric acid is also used as an acidulant in creams, gels, and liquids. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. Intolerance to citric acid in the diet is known to exist. Altered levels of citric acid have been found to be associated with maple syrup urine disease, primary hypomagnesemia, propionic acidemia, and tyrosinemia I, which are inborn errors of metabolism.
Structure
Thumb
SynonymsNot Available
Chemical FormulaC6H8O7
Average Molecular Weight192.12
Monoisotopic Molecular Weight192.027
IUPAC Name(1R,2S,5S)-2,6,6-trimethylbicyclo[3.1.1]heptan-2-ol
Traditional Name(1R,2S,5S)-2,6,6-trimethylbicyclo[3.1.1]heptan-2-ol
CAS Registry Number77-92-9
SMILES
OC(=O)CC(O)(CC(O)=O)C(O)=O
InChI Identifier
InChI=1S/C6H8O7/c7-3(8)1-6(13,5(11)12)2-4(9)10/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)
InChI KeyKRKNYBCHXYNGOX-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as bicyclic monoterpenoids. These are monoterpenoids containing exactly 2 rings, which are fused to each other.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassMonoterpenoids
Direct ParentBicyclic monoterpenoids
Alternative Parents
Substituents
  • Pinane monoterpenoid
  • Bicyclic monoterpenoid
  • Tertiary alcohol
  • Cyclic alcohol
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External DescriptorsNot Available
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point153 °CNot Available
Boiling Point310 °CWikipedia
Water Solubility592 mg/mLNot Available
logP-1.64AVDEEF,A (1997)
Predicted Properties
PropertyValueSource
logP2.56ALOGPS
logP1.89ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)19.91ChemAxon
pKa (Strongest Basic)-0.65ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity45.55 m³·mol⁻¹ChemAxon
Polarizability18.54 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
EI-MS/GC-MS
TypeDescriptionSplash KeyView
Predicted GC-MScis-2-pinanol, 1 TMS, Predicted GC-MS Spectrum - 70eV, PositiveNot AvailableSpectrum
MS/MS
TypeDescriptionSplash KeyView
Predicted MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot AvailableSpectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot AvailableSpectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot AvailableSpectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot AvailableSpectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot AvailableSpectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot AvailableSpectrum
NMRNot Available
Pathways
Pathways
Protein Targets
Enzymes
Protein NameGene NameLocusUniprot IDDetails
Pyruvate dehydrogenase E1 component subunit beta, mitochondrialPDHB3p21.1-p14.2P11177 details
Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrialPDHA1Xp22.1P08559 details
Aspartate aminotransferase, mitochondrialGOT216q21P00505 details
Aconitate hydratase, mitochondrialACO222q13.2Q99798 details
Cytoplasmic aconitate hydrataseACO19p21.1P21399 details
6-phosphofructokinase, liver typePFKL21q22.3P17858 details
Polycystic kidney disease 2-like 1 proteinPKD2L110q24Q9P0L9 details
TransportersNot Available
Metal Bindings
Protein NameGene NameLocusUniprot IDDetails
Cytoplasmic aconitate hydrataseACO19p21.1P21399 details
6-phosphofructokinase, liver typePFKL21q22.3P17858 details
Polycystic kidney disease 2-like 1 proteinPKD2L110q24Q9P0L9 details
ReceptorsNot Available
Transcriptional FactorsNot Available
Concentrations Data
Cannabis CultivarStatusValueReferenceDetails
Alien DawgDetected and Quantified35.2 mg/g dry wt
    • Jiamin Zheng, Yil...
details
GabriolaDetected and Quantified23.0 mg/g dry wt
    • Jiamin Zheng, Yil...
details
Island HoneyDetected and Quantified32.7 mg/g dry wt
    • Jiamin Zheng, Yil...
details
QuadraDetected and Quantified10.3 mg/g dry wt
    • Jiamin Zheng, Yil...
details
Sensi StarDetected and Quantified59.3 mg/g dry wt
    • Jiamin Zheng, Yil...
details
Tangerine DreamDetected and Quantified21.1 mg/g dry wt
    • Jiamin Zheng, Yil...
details
HMDB IDNot Available
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN IDNot Available
PubChem Compound6428289
PDB IDNot Available
ChEBI IDNot Available
References
General References
  1. Ren JG, Seth P, Ye H, Guo K, Hanai JI, Husain Z, Sukhatme VP: Citrate Suppresses Tumor Growth in Multiple Models through Inhibition of Glycolysis, the Tricarboxylic Acid Cycle and the IGF-1R Pathway. Sci Rep. 2017 Jul 3;7(1):4537. doi: 10.1038/s41598-017-04626-4. [PubMed:28674429 ]
  2. Caudarella R, Vescini F, Buffa A, Stefoni S: Citrate and mineral metabolism: kidney stones and bone disease. Front Biosci. 2003 Sep 1;8:s1084-106. doi: 10.2741/1119. [PubMed:12957820 ]
  3. Costello LC, Franklin RB: Testosterone and prolactin regulation of metabolic genes and citrate metabolism of prostate epithelial cells. Horm Metab Res. 2002 Aug;34(8):417-24. doi: 10.1055/s-2002-33598. [PubMed:12198595 ]

Enzymes

General function:
Involved in catalytic activity
Specific function:
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:
PDHB
Uniprot ID:
P11177
Molecular weight:
39233.1
General function:
Involved in oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor
Specific function:
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:
PDHA1
Uniprot ID:
P08559
Molecular weight:
43295.255
General function:
Involved in transferase activity, transferring nitrogenous groups
Specific function:
Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). Plays a key role in amino acid metabolism. Important for metabolite exchange between mitochondria and cytosol. Facilitates cellular uptake of long-chain free fatty acids.
Gene Name:
GOT2
Uniprot ID:
P00505
Molecular weight:
47517.285
General function:
Involved in metabolic process
Specific function:
Catalyzes the isomerization of citrate to isocitrate via cis-aconitate (By similarity).
Gene Name:
ACO2
Uniprot ID:
Q99798
Molecular weight:
85424.745
General function:
Involved in metabolic process
Specific function:
Iron sensor. Binds a 4Fe-4S cluster and functions as aconitase when cellular iron levels are high. Functions as mRNA binding protein that regulates uptake, sequestration and utilization of iron when cellular iron levels are low. Binds to iron-responsive elements (IRES) in target mRNA species when iron levels are low. Binding of a 4Fe-4S cluster precludes RNA binding. Catalyzes the isomerization of citrate to isocitrate via cis-aconitate (By similarity).
Gene Name:
ACO1
Uniprot ID:
P21399
Molecular weight:
98398.14
General function:
Involved in 6-phosphofructokinase activity
Specific function:
Catalyzes the third step of glycolysis, the phosphorylation of fructose-6-phosphate (F6P) by ATP to generate fructose-1,6-bisphosphate (FBP) and ADP.
Gene Name:
PFKL
Uniprot ID:
P17858
Molecular weight:
85017.825
General function:
Involved in calcium ion binding
Specific function:
May function as a subunit of an ion channel and act as a transducer of calcium-mediated signaling
Gene Name:
PKD2L1
Uniprot ID:
Q9P0L9
Molecular weight:
91981.2