Disease relevance of palmitic acid

• Hepatoma FFA and TG contained lower percentages of palmitate and higher percentages of stearate in all subcellular fractions than did liver [1].
• Hyperinsulinemia suppressed systemic and forearm lipolysis to similar degrees, however, hypoinsulinemia consistently increased systemic palmitate flux without increasing forearm palmitate release [2].
• The Salmonella typhimurium PhoP/PhoQ-activated gene pagP is required both for biosynthesis of hepta-acylated lipid A species containing palmitate and for resistance to cationic anti-microbial peptides [3].
• Transfer of palmitate from phospholipids to lipid A in outer membranes of gram-negative bacteria [3].
• Isolated working rat hearts were perfused with 11 mM [5-3H/ul-14C]glucose, 1.2 mM palmitate, and 100 microU/ml insulin and subjected to a 35-minute period of global ischemia followed by aerobic reperfusion [4].

Psychiatry related information on palmitic acid

• RESULTS: The fractional contribution from DNL to VLDL-triacylglycerol palmitate rose after alcohol consumption from 2 +/- 1% to 30 +/- 8%; nevertheless, the absolute rate of DNL (0.8 g/6 h) represented <5% of the ingested alcohol dose; 77 +/- 13% of the alcohol cleared from plasma was converted directly to acetate entering plasma [5].
• The results suggest that the palmitate method can be used to identify long-term regional changes in the turnover of brain lipids after sensory deprivation [6].
• Rates of mitochondrial and peroxisomal beta-oxidation of palmitate change during postnatal development and food deprivation in liver, kidney and heart of pigs [7].
• Furthermore, the extent of diminution of clearance of palmitate, quantified in terms of the rate of clearance for palmitate divided by that for acetate (to correct for individual differences in overall mitochondrial oxidative metabolic flux), correlated with the clinical severity of the long-chain ACD deficiency [8].
• Inhibitory effects of beta-amyrin palmitate in locomotor activity of mice were studied by combining this compound with alpha-adrenergic agonists or antagonists and a dopaminergic agonist. beta-Amyrin palmitate (2.5, 5.0 and 10.0 mg kg-1, i.p.) decreased locomotor activity of mice in a dose-dependent manner [9].

High impact information on palmitic acid

• Our results indicate that there is an unexpected connection between impaired palmitate modification of neuronal proteins and the psychiatric phenotypes associated with microdeletions of chromosome 22q11 [10].
• Synaptic strength regulated by palmitate cycling on PSD-95 [11].
• The membrane-bound form of ubiquitin was labeled with both phosphate and palmitate, and its electrophoretic mobility was altered by treatment with phospholipase A2 and a phosphatidylcholine-specific phospholipase D. Mild trypsin digestion indicated that the acyl group was not linked to the C-terminus of the protein [12].
• Thus, activation-induced removal of palmitate provides an explanation for activation-induced shifts of alpha s to the cytosol [13].
• Attachment of a palmitate lipid to peptides based on the third intracellular loop of protease-activated receptor 1 (PAR1) or PAR4 (refs. 3-5) yielded potent inhibitors of thrombin-mediated aggregation of human platelets [14].

Chemical compound and disease context of palmitic acid

• These results are in contrast with the lack of effect of globomycin on the RTEM-beta-lactamase of E. coli which has no detectable hydrophobic membrane form and was not labeled with palmitate or glycerol [15].
• The presence of cysteine in the cytoplasmic domain of the vesicular stomatitis virus glycoprotein is required for palmitate addition [16].
• In aerobic hearts not subjected to ischemia, Etomoxir (10(-6) M) increased glucose oxidation both in the presence and absence of palmitate, while 10(-9) M Etomoxir had no effect [17].
• Oleate activates phosphatidylinositol 3-kinase and promotes proliferation and reduces apoptosis of MDA-MB-231 breast cancer cells, whereas palmitate has opposite effects [18].
• Freshly isolated Morris Hepatoma 7777 cells were prepared for a study of the utilization of palmitate and beta-hydroxybutyrate as metabolic fuels compared to other major energy substrates (glucose and glutamine) [19].

Biological context of palmitic acid

• Post-translational modification by the lipid palmitate is crucial for the correct targeting and function of many proteins [20].
• Acylation of cellular proteins with the fatty acids myristate or palmitate represents an important mechanism for the co- or posttranslational modification of proteins [21].
• Instead, the high-carbohydrate delivery in conjunction with insulin therapy increased the proportion of de novo-synthesized palmitate in VLDL TG from 13+/-5% (C) to 34+/-14% (I+G), with a corresponding decreased amount of palmitate from lipolysis [22].
• 13C NMR spectra for samples containing carboxyl 13C-enriched palmitate, human serum albumin, and phospholipid vesicles or native lipoproteins (all samples at pH 7.4, 37 degrees C) exhibited up to six carboxyl NMR resonances corresponding to FA bound to distinct binding sites on albumin and nonalbumin components [23].
• Unsaturated fatty acids rescue palmitate-induced apoptosis by channeling palmitate into triglyceride pools and away from pathways leading to apoptosis [24].

Anatomical context of palmitic acid

• This demonstrates that Ras must bind to membranes in order to transmit a signal for transformation, but that either myristate or palmitate can perform this role [25].
• Palmitate uptake by hepatocyte monolayers. Effect of albumin binding [26].
• In human myotubes in vitro, we measured suppressibility (glucose suppression of FOx) and adaptability (an increase in FOx in the presence of high palmitate concentration) [27].
• Results: Adipose tissue palmitate release was greater from forearm than whole body (5.97 +/- 0.75 vs. 3.84 +/- 0.34 mumol.kg fat-1.min-1, respectively, P less than 0.005, n = 22 subjects) [2].
• 97% of the total laurate omega-oxidative activity recovered was found in the microsomes, but 32% of palmitate omega-oxidative activity was present in the cytosol [28].

Associations of palmitic acid with other chemical compounds

• Here, we identify palmitate cycling on PSD-95 at the synapse and find that palmitate turnover on PSD-95 is regulated by glutamate receptor activity [11].
• The 21-kD proteins encoded by ras oncogenes (p21Ras) are modified covalently by a palmitate attached to a cysteine residue near the carboxyl terminus [25].
• Each of these secretagogues elicited little, if any, IS from the isolated, perfused "fasted" pancreas when tested simply on the background of 3 mM glucose, but all became extremely potent when 0.5 mM palmitate was also included in the medium [29].
• Islets isolated from male Sprague-Dawley rats were exposed to palmitate (0.125 or 0.25 mM), oleate (0.125 mM), or octanoate (2.0 mM) during culture [30].
• Addition of exogenous arachidonate increased tissue cAMP and media PGE at both 750 and 1,650 mosM, whereas palmitate and stearate had no effect on cAMP at either osmolality [31].
• After palmitate culturing, ROZ reversed the inhibitory effect on glucose-stimulated insulin release [32].
• Together, our findings in hepatocytes indicate that palmitate inhibited insulin signal transduction through JNK activation and that accelerated beta-oxidation of palmitate caused excess electron flux in the mitochondrial respiratory chain, resulting in increased ROS generation [33].

Gene context of palmitic acid

• A NMT1 strain with deletions of all four FAAs is still viable at 30 degrees C on media containing myristate, palmitate, or oleate as the sole carbon source--indicating that S. cerevisiae contains at least one other FAA which directs fatty acids to beta-oxidation pathways [34].
• We show that TIP1 binds the acyl group palmitate, that it can rescue the morphological, temperature sensitivity, and yeast casein kinase2 localization defects of the yeast S-acyl transferase mutant akr1Delta, and that inhibition of acylation in wild-type Arabidopsis roots reproduces the Tip1- mutant phenotype [35].
• Here we demonstrate that Snc proteins undergo a single posttranslational modification with the addition of a palmitate moiety to Cys-95 in Snc1 [36].
• We first cloned desat1 in the Tai strain and report here functional expression of desat1 in CS and Tai. In both strains, the Desat1 enzymes have the same Delta9 specificity and preferentially use palmitate as a substrate, leading to the synthesis of omega7 fatty acids [37].
• The N-terminal domain (ShhNp) of Sonic hedgehog protein, generated by cholesterol-dependent autoprocessing and modification at the C terminus and by palmitate addition at the N terminus, is the active ligand in the Shh signal transduction pathway [38].
• The inhibitory effect of palmitate on PDK1 and Akt was diminished in PKCtheta-deficient mouse embryonic fibroblasts (MEFs) by treating C2C12 myotubes with PKCtheta pseudosubstrates [39].

Analytical, diagnostic and therapeutic context of palmitic acid

• Neither plasma palmitate concentrations nor respiratory quotient by indirect calorimetry differed between men and women [40].
• The inhibitory effect of previous palmitate was similar when co-culture was performed with 5.5, 11, or 27 mM glucose [30].
• METHODS AND RESULTS: Myocardial glycogen of isolated, working rat hearts was radiolabeled, after 30 minutes of substrate-free glycogen depletion, by perfusion for 60 minutes with buffer designed to stimulate resynthesis of glycogen (1.2 mmol/L palmitate, 11 mmol/L [U-14C]- or [5-3H]glucose, 0.5 mmol/L lactate, and 100 microU/mL insulin) [41].
• Regional assessment of myocardial metabolic integrity in vivo by positron-emission tomography with 11C-labeled palmitate [42].
• Tomograms were obtained after intravenous injection of 5 to 10 mCi of 11C-labeled palmitate, a physiological substrate of myocardium [43].

References