acetyl CoA (72-89-9) Physical and Chemical Properties
acetyl CoA
Central metabolic cofactor and acetyl donor commonly used as a substrate and analytical standard in enzymology, metabolomics and biochemical R&D.
| CAS Number | 72-89-9 |
| Family | Acyl-CoAs (CoA derivatives) |
| Typical Form | Powder or crystalline solid |
| Common Grades | BP, EP, JP |
Acetyl CoA is an acyl‑CoA thioester: the acetyl group is linked to coenzyme A via an S‑acetyl thioester on the pantetheine sulfhydryl. Structurally it combines a 3′‑phosphoadenosine diphosphate moiety, a pantetheine arm and the acetyl‑thioester linkage, producing a multifunctional, highly polar molecule with multiple ionizable phosphate groups and hydrogen‑bonding functionalities. The molecule contains multiple stereocenters and dense functionality (hydroxyls, amide linkages, phosphoester groups and a purine base) that determine both reactivity (thioester lability and acetyl transfer) and protein/enzymatic recognition.
Electronic and physicochemical features include a large topological polar surface area and numerous hydrogen‑bond donors and acceptors, yielding high aqueous solubility and very low intrinsic lipophilicity. At physiological pH the phosphate groups are deprotonated and the conjugate forms are highly anionic, so cellular transport and membrane crossing are mediated by carrier proteins and enzymatic systems rather than by passive diffusion. Chemically, the principal reactive locus is the thioester bond: it is kinetically activated toward nucleophilic attack and trans‑acylation but thermodynamically stabilized in enzyme active sites; the phosphoester and ribose features are stable under mild conditions but susceptible to hydrolytic or enzymatic cleavage under aggressive chemical conditions.
In metabolism and biotechnology, acetyl CoA is a central metabolic hub: it serves as the acetyl donor in biosynthetic pathways (fatty‑acid and sterol synthesis), is the two‑carbon donor entering the tricarboxylic acid cycle (via citrate synthase), and functions as the acetylating agent for protein post‑translational modification (e.g., lysine acetylation). Common commercial grades reported for this substance include: BP, EP, JP.
Molecular Overview
Molecular Weight and Composition
- Molecular formula: C23H38N7O17P3S
- Molecular weight (reported): \(809.6\,\mathrm{g}\,\mathrm{mol}^{-1}\)
- Exact / monoisotopic mass: \(809.12577494\,\mathrm{Da}\)
- Heavy atom count: 51
- Structural complexity (computed): 1380
- Defined stereocenters: 5
- Physical description (experimental): Solid
These values reflect the full coenzyme A scaffold bearing three phosphate groups, an adenine nucleoside, and the acetylated pantetheine arm; the high molecular weight and heavy atom count are consistent with a cofactor-sized metabolite.
Charge, Polarity, and LogP
- Computed XLogP3: -5.6 (unitless)
- Topological polar surface area (TPSA): \(389\,\text{Å}^2\)
- Hydrogen-bond donors: 9
- Hydrogen-bond acceptors: 22
- Rotatable bonds: 20
- Formal charge (model representation): 0
Although the modeled formal charge is reported as 0 in the canonical representation, the molecule contains multiple phosphate groups that are ionizable; under physiological conditions acetyl CoA exists predominantly in anionic forms with substantial negative charge localized on the phosphate oxygens. The very negative XLogP and large TPSA indicate strong aqueous solubility, extensive hydration, and poor passive membrane permeability; these properties explain the dependence on carrier proteins and enzyme‑mediated transport for intracellular distribution.
Biochemical Classification
- Classification (chemical class): Fatty Acyls → Fatty esters → Fatty acyl CoAs
- Functional class: acyl donor; coenzyme; metabolite; effector
Acetyl CoA is the prototypical short‑chain acyl‑CoA: it functions enzymatically as an activated acetyl donor in transferase reactions and as the central two‑carbon unit in catabolic and anabolic pathways. The pantetheine arm provides the flexible tether that positions the thioester for enzymatic catalysis.
Chemical Behavior
Stability and Degradation
The thioester linkage (S‑acetyl) is the principal chemically labile site. Thioesters are more susceptible to nucleophilic attack and hydrolysis than corresponding esters or amides; consequently acetyl CoA is chemically labile in aqueous solution relative to fully esterified derivatives. Hydrolytic destabilization is accelerated under alkaline conditions and in the presence of nucleophiles or catalytic metal ions. Enzymatic systems (thioesterases and transferases) catalyze cleavage or transfer under physiological conditions, and non‑enzymatic degradation can occur during prolonged storage in aqueous solutions or when exposed to elevated temperatures. Oxidative modification of the sulfur atom (sulfoxide or sulfone formation) is a potential degradation pathway under oxidizing conditions but requires stronger oxidants than routine aqueous handling.
Hydrolysis and Transformations
- The primary non‑enzymatic transformation is hydrolysis of the thioester to yield acetate (or acyl‑derived products) plus free coenzyme A.
- Acetyl transfer (trans‑acylation) to nucleophiles (amines, hydroxyls, thiols) is the fundamental reactivity exploited by acetyltransferases in biological systems; non‑enzymatic acetylation of strongly nucleophilic targets can occur under activating conditions.
- Phosphoester linkages (adenosine diphosphate and 3′‑phosphate) are chemically robust under neutral pH but will hydrolyze under strong acidic or basic conditions or in the presence of phosphatases.
- Enzymatic conversions include condensation with oxaloacetate (citrate synthase), formation of malonyl‑CoA (acetyl‑CoA carboxylase), and participation in numerous acyl‑transfer and decarboxylation reactions.
No experimentally established numerical hydrolysis rates are provided in the current data context.
Biological Role
Functional Role and Pathways
Acetyl CoA is a central metabolic intermediate and acetyl donor. Its principal biological functions include:
- Entry of acetyl units into the tricarboxylic acid (TCA) cycle via condensation with oxaloacetate to form citrate.
- Serving as the two‑carbon building block in fatty‑acid and sterol biosynthesis.
- Acting as the acetyl group donor for enzymatic and non‑enzymatic acetylation reactions, including lysine acetylation of proteins, which modulates enzyme activity and gene regulation.
- Participation in catabolic oxidation of fatty acids and in the metabolism of many amino acids through acyl‑CoA intermediates.
These roles are mediated by a wide array of enzymes and protein complexes that recognize the coenzyme A scaffold and catalyze acyl transfer or carbon‑carbon bond formation.
Physiological and Cellular Context
Documented tissue locations include: Adipose Tissue, Brain, Platelet, Prostate, Skeletal Muscle, Spleen.
Reported cellular locations include: Cytoplasm, Endoplasmic reticulum, Extracellular, Golgi apparatus, Membrane, Mitochondria, Nucleus, Peroxisome.
The subcellular distribution reflects functional compartmentalization: mitochondrial acetyl CoA is primarily linked to oxidative metabolism, while cytosolic and nuclear pools are used for biosynthetic acetylation and for regulation of gene expression via histone acetylation. Transport and compartmental exchange are mediated by specific transporters and metabolic shuttles.
Identifiers and Synonyms
Registry Numbers and Codes
- CAS number: 72-89-9
- EC number: 200-790-9
- UNII: 76Q83YLO3O
- ChEBI: CHEBI:15351
- ChEMBL: CHEMBL1230809
- DSSTox Substance ID: DTXSID30992686
- HMDB: HMDB0001206
- KEGG ID: C00024
- LIPID MAPS ID: LMFA07050281
- Metabolomics Workbench ID: 50043
- NCI Thesaurus Code: C199
- Nikkaji Number: J1.124.268E
- PharmGKB ID: PA166178658
- Pharos Ligand ID: 3X8AK4LDLTKN
- Wikidata: Q715317
Structural identifiers:
- SMILES: CC(=O)SCCNC(=O)CCNC(=O)C@@HO
- InChI: InChI=1S/C23H38N7O17P3S/c1-12(31)51-7-6-25-14(32)4-5-26-21(35)18(34)23(2,3)9-44-50(41,42)47-49(39,40)43-8-13-17(46-48(36,37)38)16(33)22(45-13)30-11-29-15-19(24)27-10-28-20(15)30/h10-11,13,16-18,22,33-34H,4-9H2,1-3H3,(H,25,32)(H,26,35)(H,39,40)(H,41,42)(H2,24,27,28)(H2,36,37,38)/t13-,16-,17-,18+,22-/m1/s1
- InChIKey: ZSLZBFCDCINBPY-ZSJPKINUSA-N
Synonyms and Biological Names
Common and deposited synonyms appearing in identifier lists include (selected exact strings):
- Acetyl Coenzyme A
- Acetyl CoA
- Acetyl-CoA
- ACETYL COENZYME A
- acetyl-CoA
- S-Acetyl coenzyme A
- CoA, Acetyl
- S-acetyl-CoA
- S-acetyl-coenzyme A
- AcCoA
- Coenzyme A, S-acetate
- Acetyl CoALi3 . 3H2O
- ac-CoA
(Additional depositor-supplied synonyms and systematic names are recorded in identifier metadata.)
Safety and Handling Overview
Handling and Storage of Biochemical Materials
- General handling: Treat acetyl CoA as a labile biochemical reagent. Because of the activated thioester linkage it is susceptible to hydrolysis and non‑enzymatic acetyl transfer; minimize exposure to aqueous solutions at elevated pH, avoid prolonged incubation at ambient temperature, and reduce the number of freeze–thaw cycles. Use appropriate personal protective equipment (gloves, eye protection, laboratory coat) and adopt procedures to contain aerosols and spills.
- Storage: Preserve material integrity by storing in dry, cold conditions and minimizing exposure to moisture and oxidants; lyophilized storage or cold storage under inert atmosphere reduces hydrolytic and oxidative degradation. Exact storage form (salt, hydrate) and conditions should follow supplier or batch‑specific guidance.
- Waste and decontamination: Dispose of aqueous and solid residues according to institutional biosafety and chemical safety procedures for biologically active reagents. Deactivation by thorough dilution and enzymatic or chemical hydrolysis under controlled conditions is standard practice for small quantities prior to disposal.
- Regulatory and transport: For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
No experimentally established specific hazard classification, GHS codes, transport numbers or storage temperature setpoints are provided in the current data context.
