Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Linoleate monohydroperoxide (L-HPO), methyl linoleate monohydroperoxide (ML-HPO), and methyl hydroperoxy-epoxy-octadecenoate (ML-X) inhibited state 3 respiration of mitochondria when palmitate, palmitoyl CoA, or L-palmitoylcarnitine was used as a substrate. L-HPO was the most effective, and 50% inhibition of palmitate-supported respiration was observed with 2, 3.3, and 6.5 nmol/mg protein of L-HPO, ML-X, and ML-HPO, respectively. Almost the same values were obtained when palmitoyl CoA or L-palmitoylcarnitine was used in place of palmitate. L-HPO inhibited the reaction of beta-oxidation in mitochondria in a similar concentration range (4 nmol/mg protein for 50% inhibition) when L-palmitoylcarnitine was used as a substrate. L-HPO also inhibited the formation of 3-hydroxypalmitoylcarnitine from the same substrate. Carnitine palmitoyltransferase activity of mitochondria was inhibited by L-HPO, 50% inhibition occurring at 12 nmol/mg protein. These inhibitory effects of L-HPO were weaker when ATP was removed by hexokinase and glucose. ATP-dependent formation of carnitine ester of L-HPO was also suggested. It was deduced that L-HPO (and ML-X and ML-HPO after hydrolysis) was converted to carnitine ester and inhibited the palmitate metabolism at the site(s) of intramitochondrial carnitine palmitoyltransferase (and possibly acyl CoA dehydrogenase).
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PMID:Inhibition of palmitate oxidation in mitochondria by lipid hydroperoxides. 672 34

We have previously reported that cis-unsaturated free fatty acids, e.g. linoleic acid, introduced as free fatty acids into lymphocyte membranes inhibited surface immunoglobulin capping. Trans-unsaturated and saturated free fatty acids had no effect. These results were interpreted as being due to perturbation of specific membrane lipid domains. Corps, A. N., Pozzan, T., Hesketh, T. R., and Metcalfe, J. C. (1980) J. Biol. Chem. 255, 10566-10568) in a recent paper argued, however, that linoleic acid causes depletion of ATP, as measured by the luciferin/luciferase assay, and respiratory uncoupling. We now present data showing that under the same conditions as the capping inhibition, there is neither ATP depletion, as found using a hexokinase/glucose-6-phosphate dehydrogenase assay, nor respiratory uncoupling. Linoleic acid produces artifacts in ATP measurements made using the luciferin/luciferase assay which leads to an erroneous conclusion regarding the ATP dependence of the capping inhibition.
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PMID:Inhibition of cap formation on lymphocytes by free fatty acids is not mediated by a depletion of ATP. 706 13