Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.1.8 (acyl-CoA dehydrogenase)
 785 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urinary analysis of the pattern of 23 organic acid metabolites derived from fatty acids in three patients with general (medium-chain) acyl-CoA dehydrogenase deficiency was performed. Although there exist quantitative differences in the excreted amounts of the different metabolites in the three patients the qualitative picture was the same. The excretion of adipic, suberic and sebacic acids was substantial, whereas that of dodecanedioic acid was within or just above control limit. The monounsaturated C6-C10-dicarboxylic acid excretion was only marginally or not increased. 5-OH-hexanoic acid and hexanoylglycine were excreted in excessive amounts, whereas 7-OH-octanoic acid, 9-OH-decanoic acid, octanoylglycine and decanoylglycine were excreted in limited amounts. The excreted amounts of 6-OH-hexanoic, 8-OH-octanoic and 10-OH-decanoic acids were not or only marginally elevated compared to controls. In one of the patients the excretion of ethylmalonic and methylsuccinic acids was enhanced, whereas the excretion of these two acids in the two other patients was comparable to that in controls. The urinary excretion of hexanoic, octanoic, decanoic and dodecanoic acids was just a little above the control limit, whereas the esterified hexanoic and octanoic acids were excreted in appreciable amounts. It is argued that the microsomal omega- and omega-1-oxidation systems are involved in the dicarboxylic and omega-1-OH-monocarboxylic acids formation at C10 and C12 level and that the C8-C6-dicarboxylic and omega-1-OH-monocarboxylic acids are formed from higher chained acids by beta-oxidation in both mitochondria and peroxisomes.
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PMID:General (medium-chain) acyl-CoA dehydrogenase deficiency (non-ketotic dicarboxylic aciduria): quantitative urinary excretion pattern of 23 biologically significant organic acids in three cases. 661 73

In mice and other sensitive species, PPARalpha mediates the induction of mitochondrial, microsomal, and peroxisomal fatty acid oxidation, peroxisome proliferation, liver enlargement, and tumors by peroxisome proliferators. In order to identify PPARalpha-responsive human genes, HepG2 cells were engineered to express PPARalpha at concentrations similar to mouse liver. This resulted in the dramatic induction of mRNAs encoding the mitochondrial HMG-CoA synthase and increases in fatty acyl-CoA synthetase (3-8-fold) and carnitine palmitoyl-CoA transferase IA (2-4-fold) mRNAs that were dependent on PPARalpha expression and enhanced by exposure to the PPARalpha agonist Wy14643. A PPAR response element was identified in the proximal promoter of the human HMG-CoA synthase gene that is functional in its native context. These data suggest that humans retain a capacity for PPARalpha regulation of mitochondrial fatty acid oxidation and ketogenesis. Human liver is refractory to peroxisome proliferation, and increased expression of mRNAs for the peroxisomal fatty acyl-CoA oxidase, bifunctional enzyme, or thiolase, which accompanies peroxisome proliferation in responsive species, was not evident following Wy14643 treatment of cells expressing elevated levels of PPARalpha. Additionally, no significant differences were seen for the expression of apolipoprotein AI, AII, or CIII; medium chain acyl-CoA dehydrogenase; or stearoyl-CoA desaturase mRNAs.
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PMID:Identification of peroxisome proliferator-responsive human genes by elevated expression of the peroxisome proliferator-activated receptor alpha in HepG2 cells. 1137 53

The purpose of this study was to determine if there were differences in the capacity of skeletal muscle from morbidly obese Black and White American women to oxidize fatty acids. The oxidation rates of (14)C-palmitate, (14)C-palmitoyl-CoA, and (14)C-palmitoyl-carnitine were measured in whole homogenates of rectus abdominus from Black and White women who were similar in age and body mass index (BMI). The activities of muscle citrate synthase (CS), beta-hydroxy acyl-CoA dehydrogenase (beta-HAD), and mitochondrial and microsomal acyl-CoA synthetase (ACS) were measured in the 2 groups. The results showed that the rate of (14)C-palmitate oxidation by muscle of Black women was 25% that of Whites (8.7 +/- 1.5 v 34.4 +/- 6.8 nmol (14)CO(2) produced/gram tissue wet weight/ hour; P <.05), but the rates of (14)C-palmitoyl-CoA and (14)C-palmitoyl-carnitine oxidation were not different in the 2 groups. No differences were found in the activities of CS or beta-HAD. However, the activities of both mitochondrial and microsomal ACS were lower in the Black women than the Whites (mitochondrial ACS 25.1 +/- 3.9 v 36.4 +/- 5.0 nmol/mg protein/min; P <.05; microsomal ACS 6.2 +/- 0.5 v 8.5 +/- 0.5; nmol/mg protein/min; P <.005). The lower rate of palmitate oxidation, and the lack of differences in the rates of palmitoyl-CoA and palmitoyl-carnitine oxidation indicate that there is a defect in the activation of the fatty acid in the muscle of the Black women. This was confirmed by the decrease in mitochondrial ACS activity in the Black women. The decreased fatty acid oxidation by skeletal muscle of obese Black women could result in shunting these fuels from muscle to adipose tissue for storage, which may contribute to the maintenance of obesity in the Black women.
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PMID:Fatty acid oxidation by skeletal muscle homogenates from morbidly obese black and white American women. 1280 Jan

Subcellular proteomics, which includes isolation of subcellular components prior to a proteomic analysis, is advantageous not only in characterizing large macro-molecular complexes such as organelles but also in elucidating mechanisms of protein transport and organelle biosynthesis. Because of the high sensitivity achieved by the present proteomics technology, the purity of samples to be analyzed is important for the interpretation of the results obtained. In the present study, peroxisomes isolated from rat liver by usual cell fractionation were further purified by immunoisolation using a specific antibody raised against a peroxisomal membrane protein, PMP70. The isolated peroxisomes were analyzed by SDS-PAGE combined with liquid chromatography/mass spectrometry. Altogether 34 known peroxisomal proteins were identified in addition to several mitochondrial and microsomal proteins. Some of the latter may reside in the peroxisomes as well. Analysis of membrane fractions identified all known peroxins except for Pex7. Two new peroxisomal proteins of unknown function were of high abundance. One is a bi-functional protein consisting of an aminoglycoside phosphotransferase-domain and an acyl-CoA dehydrogenase domain. The other is a newly identified peroxisome-specific isoform of Lon protease, an ATP-dependent protease with chaperone-like activity. The peroxisomal localization of the protein was confirmed by immunological techniques. The peroxisome-type Lon protease, which is distinct from the mitochondrial isoform, may play an important role in the peroxisomal biogenesis.
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PMID:Proteomic analysis of rat liver peroxisome: presence of peroxisome-specific isozyme of Lon protease. 1456 59