ubiquinone and lauric-acid

UCP2 (the lowest Km values: 20 and 29 microm, respectively) for omega-6 polyunsaturated FAs (PUFAs), all-cis-8,11,14-eicosatrienoic and all-cis-6,9,12-octadecatrienoic acids, which are also the most potent agonists of the nuclear PPARbeta receptor in the activation of UCP2 transcription. omega-3 PUFA, cis-5,8,11,14,17-eicosapentaenoic acid had lower affinity (Km, 50 microm), although as an omega-6 PUFA, arachidonic acid exhibited the same low affinity as lauric acid (Km, approximately 200 microm). These findings suggest a possible dual role of some PUFAs in activating both UCPn expression and uncoupling activity. UCP2 (UCP3)-dependent H+ translocation activated by all tested FAs was inhibited by purine nucleotides with apparent affinity to UCP2 (reciprocal Ki) decreasing in order: ADP > ATP approximately GTP > GDP >> AMP. Also [3H]GTP ([3H]ATP) binding to isolated Escherichia coli (Kd, approximately 5 microm) or yeast-expressed UCP2 (Kd, approximately 1.5 microm) or UCP3 exhibited high affinity, similar to UCP1. The estimated number of [3H]GTP high affinity (Kd, <0.4 microm) binding sites was (in pmol/mg of protein) 182 in lung mitochondria, 74 in kidney, 28 in skeletal muscle, and approximately 20 in liver mitochondria. We conclude that purine nucleotides must be the physiological inhibitors of UCPn-mediated uncoupling in vivo.

Topics: Adenosine Triphosphate; Biological Transport; Carrier Proteins; Coenzymes; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Guanosine Triphosphate; Humans; Ion Channels; Kinetics; Lauric Acids; Ligands; Liposomes; Membrane Transport Proteins; Mitochondria; Mitochondrial Proteins; Proteins; Protons; Tritium; Ubiquinone; Uncoupling Protein 2; Uncoupling Protein 3; Yeasts

Poly(ethylene imine) (PEI) was used for the complexation of dodecanoic acid (C12) resulting in a poly(ethylene imine) dodecanoate complex (PEI-C12) with a lamellar nanostructure and a repeat unit of 2.9 nm. PEI-C12 was doped with coenzyme Q10 and the hormone triiodothyronine as typical hydrophobic and pharmacological active compounds, respectively. The PEI-C12 acts as a guest matrix that dissolves both molecules up to weight uptakes of about 20% (w/w) and 15% (w/w), respectively, both without crystallization. Agglomerate-free dispersions of core-shell type nanoparticles were developed. Ratios of PEI to C12 of 2:1 or higher were found to be suitable for this purpose. The particles exhibit hydrodynamic diameters in the range of 80-150 nm, which depend on the preparation conditions. Each particle consists of a relatively compact core surrounded by a diffuse corona. PEI-C12 forms the core, while non-complexed PEI acts as a cationic-active dispersing agent. It was found that the nanoparticles show high zeta potentials (approximately +40 mV) and are stable in NaCl solutions at concentrations of up to 0.3 mol x l(-1). The stabilization of the nanoparticles results from a combination of ionic and steric contributions. A variation of the pH value was used to activate the dissolution of the particles. The PEI-C12 nanoparticles may have potential as carriers for hydrophobic drugs.

Topics: Coenzymes; Drug Carriers; Drug Stability; Lauric Acids; Solubility; Triiodothyronine; Ubiquinone