Disease relevance of alpha-Bromopalmitic acid

• The addition of 2-bromopalmitate, an inhibitor of fatty acid oxidation that inhibited glucose cycling in hepatocytes from IDDM rats, had no effect on glucose cycling in cells from ZDF rats [1].
• To address the importance of these fatty acylations to coronavirus infection, we exposed infected cells to 2-bromopalmitate (2-BP), a specific PAT inhibitor [2].

High impact information on alpha-Bromopalmitic acid

• Site-directed mutagenesis and 2-bromopalmitate treatment provide evidence that palmitoylation of the cytoplasmic Cys245 is a negative regulatory mechanism of Ser258 phosphorylation [3].
• In contrast, 2-bromopalmitate, a non-metabolizable analog of palmitate, did not alter the phosphorylation of AMPK and acetyl-CoA carboxylase [4].
• Filopodia induction is blocked by mutations of the palmitoylated sites or by treatment with 2-bromopalmitate, an agent that inhibits protein palmitoylation [5].
• Inhibition of protein palmitoylation, raft localization, and T cell signaling by 2-bromopalmitate and polyunsaturated fatty acids [6].
• Treatment of COS-1 cells with 2-bromopalmitate blocked myristoylation and palmitoylation of Fyn and inhibited membrane binding and localization of Fyn to detergent-resistant membranes (DRMs) [6].

Biological context of alpha-Bromopalmitic acid

• The threshold concentration for long-chain fatty acids was 0.05 mmol/l, and maximal inhibition occurred at 0.3 mmol/l. 2-bromopalmitate, a nonmetabolizable analog, had no effect, suggesting that fatty acids must be metabolized to change ACC gene expression [7].
• 8. 2-Bromopalmitate, an inhibitor of fatty acid oxidation, did not influence the inhibition of glycolysis by the diphosphonates [8].
• In vitro we found that 2-bromopalmitate and palmitate compete equivalently for the same ligand binding sites on albumin and intestinal fatty acid binding protein, and activation by ACS was stereoselective for the R-isomer [9].
• Regulation of fatty acid synthesis and esterification in rat epididymal adipose tissue: effects of insulin, palmitate and 2-bromopalmitate [proceedings] [10].
• 2-Bromopalmitate and 2-bromopalmitoyl-CoA have been shown to inhibit a variety of enzymes and proteins associated with lipid metabolism [11].

Anatomical context of alpha-Bromopalmitic acid

• At a concentration of 0.2 mM, 2-bromostearate, 2-bromopalmitate and etomoxir (all CPT I inhibitors) potentiated GSIS by the pancreas and inhibited palmitate oxidation in islets [12].
• Addition of the palmitoylation inhibitor 2-bromopalmitic acid to substrate-treated cells blocked palmitoylation and diminished substrate-mediated plasma membrane fluorescence [13].
• The enhanced association with mitochondria from fasted animals was inhibited by 2-bromopalmitate [14].
• In rat pancreatic islets, 2-bromopalmitate, cerulenin, and polyunsaturated fatty acids, all of which suppress protein acyltransferase activity, blocked the distal inhibitory effects of norepinephrine in a concentration-dependent manner [15].
• Inhibitors of fatty acid oxidation, 2-bromopalmitic acid (Br-C16) and 4-bromocrotonic acid (Br-C4) were examined for their effect on glucose transport in 3T3-L1 adipocytes [16].

Associations of alpha-Bromopalmitic acid with other chemical compounds

• Lyn was displaced from DRMs under the influence of DL-alpha-hydroxymyristic acid and 2-bromopalmitic acid, agents blocking N-terminal myristoylation and palmitoylation of proteins, respectively, and after disruption of DRM integrity by depletion of plasma membrane cholesterol with beta-cyclodextrin [17].
• Fluorescence quenching studies with 2-bromopalmitate showed that a fatty acid carboxylate is close to the tryptophan in the F18W protein [18].
• Furthermore, 2-bromopalmitate also blocked the distal inhibitory actions of somatostatin, galanin, and prostaglandin E2 [15].
• These include site specific mutagenesis, and treatment of cells with inhibitors of protein palmitoylation, including 2-bromopalmitate, cerulenin, and tunicamycin [19].
• Methyl palmoxirate (100 microM) and 2-bromopalmitate (100 microM), which both inhibit transport of acyl-CoA into the mitochondria, reversibly blocked the palmitate-induced Ca2+-signals in HIT-T15 as well as in primary mouse beta-cells [20].

Gene context of alpha-Bromopalmitic acid

• On the other hand, inhibitors of mitochondrial fatty acid oxidation (palmoxirate, 2-bromopalmitate, 2-bromocaproate) attenuated the stimulatory effects of insulin on leptin release without reversing the effects of fatty acids or norepinephrine, suggesting that fatty acids do not need to be oxidized by the mitochondria to inhibit leptin release [21].
• Treatment with 2-bromopalmitate, a poorly metabolizable palmitate analog, reduced ob gene expression by 50% at 10(-4)M, but palmitate at the same concentration had no effect [22].
• Using this system we determined the residence half-life of palmitate on the dipalmitoyl substrate peptide from GAP43 as well as the EC(50) for 2-bromopalmitate, a common inhibitor of palmitoylation [23].
• In Jurkat T cells, 2-bromopalmitate blocked localization of the endogenous palmitoylated proteins Fyn, Lck, and LAT to DRMs [6].
• Finally, disrupting palmitoylation with 2-bromopalmitate disperses PSD-95/K+-channel clusters [24].

References