A toxic constituent of Xanthium strumarium, which is a selective inhibitor the adenine nucleotide translocator (ANT) in mitochondria
- Catalog No: APH-06012
- CAS Number: 77228-71-8 (free acid)
- Chemical Formula: C31H44O18S2K2
- Molecular Weight: 846.99
- Purity: > 99% determined by HPLC
- Appearance: White crystalline solid
- Solubility: Soluble in water
- Stability: See storage and handling conditions.
- Storage: Store at -20ºC
- Shipping: Ambient temperature
- Handling: Avoid exposure to oxygen and direct sunlight.
C-ATR is the dipotassium salt of Carboxyatractyloside (CAT), a diterpenoid glycoside isolated from Cocklebur seeds (Xanthium spp.). CAT is a highly toxic agent responsible for the poisonous properties of the plant burr or seedlings (Cole et al., 1980).
At Aphios, CAT is extracted from Xanthium sibiricum seeds, purified using column chromatography, and then stabilized by crystallization as the dipotassium salt C-ATR.
CAT is highly selective and potent inhibitor of mitochondrial oxidative phosphorylation. Specifically, it acts as a noncompetitive inhibitor of the adenine nucleotide translocator (ANT) in mitochondria with high affinity (Kd = 5-10 nM). ANT is the cytosolic side-specific mitochondrial ADP/ATP carrier protein. This results in stabilization of the c conformation of ANT, leading to permeability transition pore opening, loss of mitochondrial membrane potential and apoptosis.
CAT stabilizes the nucleoside binding site of ANT on the cytoplasmic side of the inner membrane (Vignais et al., 1973) and blocks the exchange of matrix ATP and cytoplasmic ADP by forming a tight binding with the ADP/ATP carrier protein (Pebay-Peyroula et al., 2003). Pebay-Peyroula et al. (2003) also demonstrated how all the chemical groups, except the primary alcohol group of the ribose moiety present in CAT, play a role in its toxicity by adding to the binding affinity of CAT to the carrier protein.
Cole R, Stuart B, Lansden J and Cox R. (1980). Isolation and redefinition of the toxic agent from Cocklebur (Xanthium strumarium). J Agric Food Chem. 28: 1330-1332.
Pebay-Peyroula E, Dahout-Gonzales C, Kahn R, Trézéguet V, Lauquin G and Brandolin G. (2003). Structure of mitochondrial ADP/ATP carrier in complex with Carboxyatractyloside. Nature. 426: 39-44.
Vignais P, Vignais P and Defaye G. (1973). Adenoside diphosphate translocation in mitochondria. Nature of the receptor site for Carboxyatractyloside (gummiferin). Biochem. 12: 1508-1519.