Malonyl CoA (524-14-1) Physical and Chemical Properties
Malonyl CoA
Central acyl‑CoA metabolite frequently used as a biochemical reagent and reference standard in lipid metabolism, enzyme assays and metabolic engineering workflows.
| CAS Number | 524-14-1 |
| Family | Fatty acyl‑CoA (acyl‑CoA) derivatives |
| Typical Form | Powder or crystalline solid |
| Common Grades | EP |
Malonyl CoA is a coenzyme A (CoA) derivative belonging to the fatty acyl–CoA structural class; chemically it is the S‑malonyl thioester of coenzyme A. The molecule couples a malonyl (propanedioyl) acyl unit to the large, multi‑functional CoA scaffold that contains an adenosine 3',5'‑diphosphate ribose, a pantetheine arm and a terminal thiol that forms the thioester linkage. Structurally this yields a high‑molecular‑weight, polyfunctional oligopolar molecule featuring multiple phosphate esters, a carboxylate, numerous hydroxyls and amide linkages, and one thioester bond linking the malonyl moiety to CoA.
Electronic and physicochemical features are dominated by the densely substituted polar headgroups (three phosphate functionalities and multiple hydroxyls and amides) and the charged carboxylate/thioester region. The high topological polar surface area and abundant hydrogen‑bond donors/acceptors make the neutral canonical form of the covalent structure highly hydrophilic in practice; at physiological \(\mathrm{pH}\) the compound exists predominantly as a multiply deprotonated anion (biologically relevant ionic states include species described as \(\ce{malonyl-CoA^{5-}}\) and related protonation states). As a consequence of this strong polarity and formal multi‑negative charge in physiological media, passive transmembrane permeability is low and membrane transport or protein binding is required for intracellular distribution.
Biochemically, Malonyl CoA is a central two‑carbon donor and regulatory metabolite in fatty acid biosynthesis and related lipid metabolic pathways. It functions both as a substrate for fatty‑acid synthase and as a regulator of mitochondrial fatty acid import via inhibition of carnitine O‑palmitoyltransferase activity. In cellular and organismal contexts it is closely controlled by synthetic and degradative enzymes (e.g., acetyl‑CoA carboxylase and malonyl‑CoA decarboxylase), and perturbations in its homeostasis are implicated in metabolic disorders affecting fatty‑acid oxidation and energy metabolism. Common commercial grades reported for this substance include: EP.
Molecular Overview
Molecular Weight and Composition
- Molecular formula: \(\ce{C24H38N7O19P3S}\).
- Molecular weight (computed): \(853.6\ \mathrm{g\,mol^{-1}}\).
- Exact/monoisotopic mass: \(853.11560417\ \mathrm{Da}\).
- Heavy atom count: 54.
- Defined stereocenters: 5.
The composition reflects the fusion of the malonyl acyl unit to the large CoA scaffold; the three phosphate groups and numerous oxygens contribute the bulk of the molecule’s mass and polar surface.
Charge, Polarity, and LogP
- Formal charge (canonical computed): 0 (neutral covalent form).
- Computed XLogP3: \(-5.9\).
- Topological polar surface area (TPSA): 426.
- Hydrogen bond donors: 10.
- Hydrogen bond acceptors: 24.
- Rotatable bond count: 22.
Interpretation: the very negative XLogP and extremely high TPSA identify Malonyl CoA as a highly water‑soluble, strongly polar compound. The combination of multiple ionizable phosphate and carboxylate groups results in strong hydration and high hydrogen‑bonding capacity; consequently, lipophilicity is very low and the molecule favors aqueous phases and protein association over partitioning into lipid bilayers without facilitated transport.
Biochemical Classification
- Structural class: Fatty acyl CoAs (fatty acyl–CoA derivatives).
- Functional class: Coenzyme A derivative; metabolic intermediate in fatty acid biosynthesis and regulator of fatty acid oxidation.
As an S‑malonyl derivative of coenzyme A, the compound is a canonical building block for chain elongation reactions in fatty‑acid synthase systems and a key regulatory metabolite that links acetyl‑CoA carboxylase activity to downstream lipid metabolism.
Chemical Behavior
Stability and Degradation
No experimentally established quantitative stability (e.g., shelf‑life or kinetic hydrolysis rates) is available in the current data context. Qualitatively, the molecule contains a labile thioester bond and multiple phosphate ester linkages; these functional groups are susceptible to hydrolytic cleavage under strongly acidic or basic conditions and to enzymatic hydrolysis under physiological conditions. The bulky and highly functionalized nature of the CoA backbone makes the compound conformationally flexible yet too large for routine small‑molecule conformer generation in standard automated procedures.
Hydrolysis and Transformations
Enzymatic transformation dominates the biologically relevant reactivity: malonyl‑CoA is a substrate for decarboxylases and transferases. Principal transformations include:
- Enzymatic decarboxylation to yield acetyl‑CoA and carbon dioxide, catalyzed by malonyl‑CoA decarboxylase.
- Thioester hydrolysis to liberate free coenzyme A and malonic acid (or its deprotonated forms), either enzymatically or under strong chemical hydrolytic conditions.
- Transfer of the malonyl unit to carrier proteins or acyl‑carrier domains during chain elongation reactions (transferase activities).
Non‑enzymatic chemical degradation is generally slower under neutral, buffered aqueous conditions but increases under extreme pH or in the presence of nucleophiles that can attack phosphate esters or the thioester carbonyl.
Biological Role
Functional Role and Pathways
Malonyl CoA is the committed two‑carbon extender unit in de novo fatty acid biosynthesis: it is carboxylated from acetyl‑CoA and serves as the donor of two‑carbon units during successive condensation and reduction cycles performed by fatty‑acid synthase (and related polyketide synthase systems). It also functions as a regulatory metabolite by inhibiting carnitine O‑palmitoyltransferase activity, thereby modulating mitochondrial uptake of long‑chain acyl‑CoAs and balancing fatty‑acid synthesis versus oxidation. Documented metabolic pathway associations include fatty acid biosynthesis and several metabolic disorders in which malonyl‑CoA metabolism is perturbed.
Physiological and Cellular Context
Reported tissue locations include adipose tissue, liver, pancreas, skeletal muscle and fibroblasts. Cellular localization involves cytosolic and microsomal compartments for biosynthesis, with regulatory effects on mitochondrial fatty‑acid import and roles in peroxisomal metabolism. Intracellular concentrations are tightly regulated by acetyl‑CoA carboxylase (synthesis) and malonyl‑CoA decarboxylase (degradation), and disturbance of these enzymes alters flux through lipid biosynthetic and catabolic pathways.
Identifiers and Synonyms
Registry Numbers and Codes
- CAS number: 524-14-1
- EC number (related enzyme inhibition note): associated with carnitine O‑palmitoyltransferase (EC 2.3.1.21) in functional descriptions.
- EC number for enzymes acting on the compound are context dependent; specific enzyme identifiers should be verified in enzyme databases or product documentation.
- InChI:
InChI=1S/C24H38N7O19P3S/c1-24(2,19(37)22(38)27-4-3-13(32)26-5-6-54-15(35)7-14(33)34)9-47-53(44,45)50-52(42,43)46-8-12-18(49-51(39,40)41)17(36)23(48-12)31-11-30-16-20(25)28-10-29-21(16)31/h10-12,17-19,23,36-37H,3-9H2,1-2H3,(H,26,32)(H,27,38)(H,33,34)(H,42,43)(H,44,45)(H2,25,28,29)(H2,39,40,41)/t12-,17-,18-,19+,23-/m1/s1 - InChIKey:
LTYOQGRJFJAKNA-DVVLENMVSA-N - SMILES:
CC(C)(COP(=O)(O)OP(=O)(O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=NC3=C(N=CN=C32)N)O)OP(=O)(O)O)[C@H](C(=O)NCCC(=O)NCCSC(=O)CC(=O)O)O - Additional registry identifiers reported: UNII LNB9YCJ9F9; ChEBI CHEBI:15531; ChEMBL CHEMBL1234355; DrugBank DB04524; HMDB HMDB0001175; KEGG C00083 / C03188.
(Identifiers above are provided verbatim from registries and supplier descriptors reported for the substance.)
Synonyms and Biological Names
Common and depositor‑supplied synonyms include (selected): Malonyl Coenzyme A; Malonyl CoA; malonyl‑CoA; MALONYL COENZYME A; CoA, Malonyl; Coenzyme A, Malonyl; S‑Malonyl‑CoA; S‑(Hydrogen malonyl)coenzyme A; S‑(hydrogen propanedioate) CoA; omega‑Carboxyacyl‑CoA. These names reflect the same covalent structure or closely related naming conventions used in biochemical contexts.
Safety and Handling Overview
Malonyl CoA is a non‑volatile, high‑molecular‑weight biochemical metabolite typically supplied as a solid or as frozen/lyophilized material by manufacturers. Typical generic precautions for handling and storage of laboratory‑grade biochemical reagents apply:
- Use appropriate personal protective equipment (gloves, safety glasses and lab coat) and engineering controls (fume hood or well‑ventilated area) when weighing or preparing solutions to avoid dust generation and direct skin contact.
- Minimize exposure to conditions that accelerate hydrolysis (extreme pH, prolonged aqueous storage) and store the material as recommended by the supplier; product‑specific storage conditions (e.g., refrigerated or frozen storage, desiccation) and stability information should be followed.
- As with all biochemical reagents, avoid release to the environment and manage waste according to institutional procedures. For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
Handling and Storage of Biochemical Materials
When used as an analytical standard or reagent, aliquoting and storage under inert conditions (low temperature, exclusion of moisture) will reduce hydrolytic degradation. Because the molecule is biologically active and participates in metabolic pathways, avoid contamination of biological systems unless experiments are designed to study its metabolic effects. For procurement and quality control, select grades suitable for the intended use (research, analytical or clinical applications) and request supporting documentation (certificate of analysis) from suppliers when necessary.
