title: Ascorbic acid 6-palmitate: a potent inhibitor of human and soybean lipoxygenase-dependent lipid peroxidation.
abstract: OBJECTIVE
  Lipoxygenases (LOX) are the key enzymes involved in the biosynthesis of leukotrienes and reactive oxygen species, which are implicated in pathophysiology of inflammatory disorders. This study was conducted to evaluate the inhibitory effect of water-soluble antioxidant ascorbic acid and its lipophilic derivative, ascorbic acid 6-palmitate (Vcpal) on polymorphonuclear lymphocyte 5-LOX and soybean 15-LOX (sLOX) in vitro.
  
  
  METHODS
  LOX activity was determined by measuring the end products, 5-hydroperoxy eicosatetraenoic acid (5-HETE) and lipid hydroperoxides, by spectrophotometric and high performance liquid chromatography methods. The substrate-dependent enzyme kinetics and docking studies were carried out to understand the nature of inhibition.
  
  
  RESULTS
  Vcpal potently inhibited 5-LOX when compared with its inhibitory effect on sLOX (IC50; 2.5 and 10.3 μm respectively, P = 0.003). Further, Vcpal inhibited 5-LOX more strongly than the known synthetic drugs: phenidone and nordihydroguaiaretic acid (P = 0.0007). Enzyme kinetic studies demonstrated Vcpal as a non-competitive reversible inhibitor of 5-LOX. In-silico molecular docking revealed high MolDock and Rerank score for Vcpal than ascorbic acid, complementing in-vitro results.
  
  
  CONCLUSIONS
  Both in-vitro and docking studies demonstrated Vcpal but not ascorbic acid as a non-competitive inhibitor of 5-LOX- and sLOX-induced lipid peroxidation, suggesting a key role for lipophilic nature in bringing about inhibition.
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Mysore, India.
authors.forename: Riyaz
authors.initials: R
authors.lastname: Mohamed
authors.forename: Shaista
authors.initials: S
authors.lastname: Tarannum
authors.forename: Manjunath
authors.initials: M
authors.lastname: Yariswamy
authors.forename: Hamse K
authors.initials: HK
authors.lastname: Vivek
authors.forename: Jalahalli M
authors.initials: JM
authors.lastname: Siddesha
authors.forename: Nataraju
authors.initials: N
authors.lastname: Angaswamy
authors.forename: Bannikuppe S
authors.initials: BS
authors.lastname: Vishwanath
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D062105:Molecular Docking Simulation; D009504:Neutrophils / Q000502:physiology; D013025:Glycine max / Q000201:enzymology
chemical_list: D000975:Antioxidants; D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid
keywords: ascorbic acid 6-palmitate; human; lipid peroxidation; lipoxygenase; soybean