Lithocholic Acid (20-18-6) Physical and Chemical Properties
Lithocholic Acid
A hydrophobic C24 steroidal bile acid supplied as a crystalline powder for use as an analytical standard and in metabolism, formulation and biochemical research workflows.
| CAS Number | 20-18-6 |
| Family | Bile acids (sterol lipid) |
| Typical Form | Powder or crystalline solid |
| Common Grades | BP, EP |
Lithocholic acid is a C24 steroidal bile acid belonging to the 5β-cholanic acid family; it is a monohydroxy bile acid formally described as a 3‑hydroxy-5β-cholan‑24‑oic acid. Structurally it comprises the tetracyclic steroid nucleus characteristic of bile acids with a single hydroxyl substituent on the A‑ring and a terminal carboxylic acid on a five‑carbon side chain. The molecule combines a largely hydrophobic, fused-ring steroid core with a small polar head (one hydroxyl and one carboxyl group), producing the classical amphipathic geometry of bile acids: a hydrophobic convex face and a polar concave face that determine micelle/aggregate behavior and membrane interactions.
Electronically, lithocholic acid is a neutral carboxylic acid in the anhydrous state but ionizes under physiological conditions to form bile‑acid anions and conjugates; the carboxylate and hydroxyl functions are the primary sites for phase II biotransformations (sulfation, glycine/taurine conjugation) and for enzymatic hydroxylations. As a consequence of the steroidal hydrocarbon scaffold and minimal polar substitution, the neutral molecule is highly lipophilic and poorly water‑soluble, whereas its conjugated and sulfated forms are substantially more polar and more readily transported and excreted.
Functionally and industrially, lithocholic acid serves as an endogenous detergent in the enterohepatic system, produced by bacterial modification of primary bile acids and participating in fat solubilization, cholesterol homeostasis and enterohepatic circulation. It is used in biochemical research as a bile‑acid standard and biochemical reagent; it is also monitored in clinical and toxicological contexts because of its physiological activity and associations with hepatic and intestinal effects. Common commercial grades reported for this substance include: BP, EP.
Molecular Attributes
Molecular Weight and Composition
- Molecular formula: \(\ce{C24H40O3}\).
- Molecular weight: 376.6 \(\mathrm{g}\,\mathrm{mol}^{-1}\).
- Exact / monoisotopic mass: 376.29774513.
- Heavy atom count: 27.
- Formal charge: 0.
- Defined atom stereocenter count: 9 (multiple chiral centers in the steroid framework).
- Molecular complexity: 574.
The composition reflects a C24 steroid backbone with two oxygenated functionalities (one hydroxyl and one carboxyl) plus saturated hydrocarbon rings and methyl substituents. The nine defined stereocenters determine the rigid three‑dimensional topology that underpins the amphipathic face‑selectivity and receptor/transport protein recognition.
InChI: InChI=1S/C24H40O3/c1-15(4-9-22(26)27)19-7-8-20-18-6-5-16-14-17(25)10-12-23(16,2)21(18)11-13-24(19,20)3/h15-21,25H,4-14H2,1-3H3,(H,26,27)/t15-,16-,17-,18+,19-,20+,21+,23+,24-/m1/s1
InChIKey: SMEROWZSTRWXGI-HVATVPOCSA-N
SMILES: C[C@H](CCC(=O)O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC[C@H]4[C@@]3(CC[C@H](C4)O)C)C
LogP and Amphiphilicity
- Computed XLogP3 (XLogP3‑AA): 6.3.
A computed XLogP3 of 6.3 is consistent with a highly lipophilic neutral molecule: the steroid nucleus creates a broad hydrophobic surface while the single hydroxyl and the carboxylic acid (when protonated) provide limited polar character. The apparent amphiphilicity arises from the segregation of polar functionality to one face of the steroid skeleton, which permits surface‑active behavior (detergent action) despite overall low aqueous solubility. At physiological \(\mathrm{pH}\) the carboxyl group is ionized and lithocholic acid occurs predominantly as more polar anionic or conjugated species, substantially lowering effective partitioning into octanol/water systems and facilitating bile salt formation and transport.
Measured solubility and practical observations: - In water: 0.38 \(\mathrm{mg}\,\mathrm{L}^{-1}\) at 25 °C (reported also as 0.000377 \(\mathrm{mg}\,\mathrm{mL}^{-1}\)). - Described as freely soluble in hot alcohol, more soluble in benzene or ether than related dihydroxy bile acids, insoluble in petroleum ether, gasoline and water, slightly soluble in glacial acetic acid (≈0.2 g in 3 mL) and soluble in about 10× its weight of ethyl acetate.
These data underline that the neutral acid is essentially non‑polar in practice and that biological solubilization relies on conjugation, sulfation or incorporation into mixed micelles.
Biochemical Properties
Biosynthesis and Metabolic Context
Lithocholic acid is a secondary bile acid produced in the gut by bacterial 7α‑dehydroxylation of chenodeoxycholic acid. It typically undergoes hepatic and extrahepatic phase I and phase II transformations: hydroxylation (for example 6α/6β and 7α hydroxylations), conjugation with glycine or taurine, and sulfation of the 3‑hydroxy group or the side‑chain carboxylate. These transformations increase water solubility and promote biliary excretion via the enterohepatic circuit.
Tissue and cellular locations reported include intestine and liver, and lithocholic acid is an identifiable human metabolite. Major metabolic routes described: formation of 3α,6β‑dihydroxy‑5β‑cholanic acid, 6α‑hydroxylation products and extensive sulfation (notably increased sulfation in glycine versus taurine conjugates in some observations). Conversion to more polar metabolites reduces detergent potency and cellular accumulation.
Reactivity and Transformations
Lithocholic acid contains two functional groups relevant to chemical and enzymatic reactivity: a secondary alcohol (3‑OH) on the steroid A‑ring and a terminal carboxylic acid on the side chain. Chemical reactivity typical for this class includes: - Acid–base chemistry of the carboxyl group (ionization to form bile‑acid anions and salts). - Esterification and salt formation at the carboxyl function (esters observed in synthetic derivative/crystal forms). - Phase I oxidations at ring positions (hydroxylations) catalyzed by hepatic cytochromes and microbial enzymes. - Phase II conjugations: amidation with glycine/taurine and sulfation; sulfation in particular markedly increases aqueous solubility and reduces membrane‑disruptive potential.
Steroid core oxidation (e.g., at C3 or other ring positions) and cleavage are not typical under mild conditions; microbial enzymes in the gut are the primary drivers of structural modification in vivo.
Stability and Degradation
Chemical and Enzymatic Degradation Pathways
Thermal behavior: when heated to decomposition, the compound emits acrid smoke and irritating fumes, indicating thermal degradation of the steroidal framework and oxygenated substituents.
Enzymatic and microbial degradation: - Gut microbiota catalyze 7α‑dehydroxylation of primary bile acids to yield lithocholic acid; other bacterial transformations can further modify the ring system. - Hepatic enzymes catalyze hydroxylations (6α/6β and 7α) and conjugations (glycine, taurine) and sulfotransferases can form sulfate esters; these pathways convert lithocholic acid into more polar metabolites that are more readily excreted. - In vitro liver homogenate experiments demonstrate conversion to 3α,6β‑dihydroxy‑5β‑cholanic acid and related metabolites; the presence of ethanol in enzymatic systems may inhibit specific hydroxylation pathways.
Environmental and chemical stability: the neutral acid is chemically stable under ambient conditions but susceptible to standard oxidation and esterification reactions of alcohols and carboxylic acids under forcing chemical conditions.
Identifiers and Synonyms
Registry Numbers and Codes
- CAS number: 20-18-6
- European Community (EC) number: 207-099-1
- UNII: 5QU0I8393U
- ChEBI: CHEBI:16325
- ChEMBL: CHEMBL1478
- HMDB: HMDB0000761
- KEGG: C03990
- LipidMaps ID (LM_ID): LMST04010003
- InChI (string):
InChI=1S/C24H40O3/c1-15(4-9-22(26)27)19-7-8-20-18-6-5-16-14-17(25)10-12-23(16,2)21(18)11-13-24(19,20)3/h15-21,25H,4-14H2,1-3H3,(H,26,27)/t15-,16-,17-,18+,19-,20+,21+,23+,24-/m1/s1 - InChIKey (string):
SMEROWZSTRWXGI-HVATVPOCSA-N - SMILES (string):
C[C@H](CCC(=O)O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC[C@H]4[C@@]3(CC[C@H](C4)O)C)C
(Identifiers above are drawn from curated registry listings and spectral annotations.)
Synonyms and Lipid Nomenclature
Common synonyms and systematic names reported include: Lithocholic Acid; Isolithocholic Acid; 3alpha‑Hydroxy‑5beta‑cholanic acid; 3alpha‑Hydroxy‑5beta‑cholan‑24‑oic acid; 3alpha‑Hydroxycholanic acid; Cholan‑24‑oic acid, 3‑hydroxy‑, (3alpha,5beta)-; 5‑beta‑Cholanic acid, 3‑alpha‑ol; 3‑Hydroxycholan‑24‑oic acid; LITHOCHOLIC ACID [EP IMPURITY]. Abbreviations encountered include LCA.
Industrial and Biological Applications
Roles in Formulations or Biological Systems
- Biological role: an endogenous secondary bile acid with detergent/solubilizing functions in the digestion and absorption of dietary lipids and fat‑soluble vitamins; participates in enterohepatic circulation and cholesterol homeostasis. It is formed by bacterial action on chenodeoxycholic acid and circulates between liver, bile ducts and intestine.
- Research use: commonly used in biochemical and pharmacological research as a reference bile acid, as a probe for bile‑acid metabolism, and in studies of bile‑acid receptor interactions and microbiome–host chemistry.
- Manufacture and sourcing: obtained by extraction from animal bile (for example ox bile in salt form) and can be prepared from other cholanic acids (e.g., deoxycholic or cholic acid) by chemical or enzymatic routes. Historically not widely produced at large scale in some regions but is commercially available in research and reagent grades.
If a concise application profile beyond the above is required for a specific industrial process, selection is typically based on the amphipathic detergent properties and the need for biological relevance in model systems.
Safety and Handling Overview
Handling and Storage of Lipid Materials
Hazard summary and handling considerations: - Signal word reported in hazard communications: Warning. - Common hazard statements reported: H315 (causes skin irritation), H319 (causes serious eye irritation), H335 (may cause respiratory irritation) in some notified classifications; hazard information may vary with formulation and impurity profile. - Acute thermal hazard: decomposition yields acrid, irritating fumes. - Chronic considerations: chronically elevated lithocholic acid levels have been associated with adverse hepatic and colonic outcomes in biological studies; experimental animal bioassays reported no clear carcinogenicity under particular dosing regimens, but promotion effects in combination with other agents have been described.
Practical handling guidance for laboratories and production: - Use appropriate personal protective equipment: eye protection, gloves and protective clothing; when weighing or handling neat material consider respiratory protection (organic‑vapor/acid‑gas cartridge with particulate filter) in accordance with risk assessment and local rules. - Containment and dust control: handle as a low‑solubility solid with potential for local irritation; avoid inhalation of dust. - Storage: recommended refrigerated storage for long‑term stability (reports indicate storage in a refrigerator). - Spill response and disposal: collect solid material and dampen with ethanol before transfer into sealed containers; wash contaminated surfaces with solvent then detergent solution; follow local environmental and waste disposal regulations.
First aid, firefighting and emergency: - Eye/skin contact: flush with copious water and seek medical attention if irritation persists. - Inhalation: remove to fresh air; seek medical attention if respiratory symptoms occur. - Firefighting: standard extinguishers such as dry chemical or carbon dioxide are applicable; burning material may evolve irritating fumes.
For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
