Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.99.3 (acyl-CoA dehydrogenase)
 1,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Docosahexaenoic acid (DHA, C22:6n-3) is essential for normal brain and retinal development. The nature and subcellular location of the terminal steps in DHA biosynthesis have been controversial. Rather than direct Delta4-desaturation of C22:5n-3, it has been proposed that this intermediate is elongated to C24:5n-3, desaturated to C24:6n-3, and "retroconverted" to DHA via peroxisomal beta-oxidation. However, this hypothesis has recently been challenged. The goal of this study was to determine the mechanism and specific enzymes required for the retroconversion step in human skin fibroblasts. Cells from patients with deficiencies of either acyl-CoA oxidase or D-bifunctional protein, the first two enzymes of the peroxisomal straight-chain fatty acid beta-oxidation pathway, exhibited impaired (5-20% of control) conversion of either [1-14C]18:3n-3 or [1-14C]22:5n-3 to DHA as did cells from peroxisome biogenesis disorder patients comprising eight distinct genotypes. In contrast, normal DHA synthesis was observed in cells from patients with rhizomelic chondrodysplasia punctata, Refsum disease, X-linked adrenoleukodystrophy, and deficiency of mitochondrial medium- or very long-chain acyl-CoA dehydrogenase. Acyl-CoA oxidase-deficient cells accumulated 2-5 times more radiolabeled C24:6n-3 than did controls. Our data are consistent with the retroconversion hypothesis and demonstrate that peroxisomal beta-oxidation enzymes acyl-CoA oxidase and D-bifunctional protein are essential for this process in human skin fibroblasts.
 ...
PMID:Peroxisomal straight-chain Acyl-CoA oxidase and D-bifunctional protein are essential for the retroconversion step in docosahexaenoic acid synthesis. 1150 May 17

Cysteinyl leukotrienes (LTs) are potent lipid mediators which are predominantly eliminated via bile. Their metabolic inactivation and degradation proceeds by beta-oxidation. However, although bile is the optimal material for analysis of LTs in man, only very sparse data on bile LT concentration under normal or pathophysiological conditions exist. The aim of the present study was to present for the first time a complete profile of endogenous LTs in human bile and to investigate the importance of bile LT analysis in peroxisomal and mitochondrial beta-oxidation deficiency. Cysteinyl LTs and their oxidation metabolites were analysed after HPLC separation by specific immunoassays or gas chromatography-mass spectrometry. Under physiological conditions, LTs are found in human bile (n = 8) in the nanomolar range with LTD4 predominating, whereas the other LTs were present in similar amounts. In bile of a patient with a peroxisome biogenesis disorder (Zellweger syndrome, ZS) LTE(4) was found to be slightly increased, whereas both omega-oxidation metabolites of LTE4, omega-hydroxy-LTE4 and omega-carboxy-LTE4, were highly increased (about 12-18 times). The beta-oxidation metabolite omega-carboxy-tetranor-LTE3 was below the detection limit (< 0.1 nmol/l; controls 1.4 +/- 1.2 nmol/l). This abnormal profile demonstrates an impaired degradation of LTs in ZS. In contrast, patients with X-linked adrenoleukodystrophy (X-ALD), medium-chain acyl CoA dehydrogenase deficiency (MCAD) as well as very long-chain acyl CoA dehydrogenase deficiency (VLCAD) did not show any differences in their biliary profile of LTs compared to controls. Increased levels of the biologically active cysteinyl LTs in the bile of patients with ZS might be of pathophysiological significance in the course of the disease, e.g. contributing to liver injury. In addition, our data confirm that the beta-oxidation of cysteinyl LTs in vivo occurs in peroxisomes and not in mitochondria.
 ...
PMID:Analysis of cysteinyl leukotrienes and their metabolites in bile of patients with peroxisomal or mitochondrial beta-oxidation defects. 1519 81

By January 2007 seven European countries had expanded, and more are considering the expansion of their newborn screening programmes by inclusion of ESI tandem mass spectrometry. We present an overview of the current status of expanded newborn screening programmes in Europe. While the first pilot programmes were initiated in 1998 in Germany, most countries started within the last 3 years. The number of disorders screened for by MS/MS ranges from two disorders (phenylketonuria and medium-chain acyl-CoA dehydrogenase deficiency) in some countries to 20 in others. The number of live births investigated per screening centre varies from 18,000 to 77,000. Few programmes have reported the number of positively identified cases and technical data, although many participate in quality assurance and proficiency test schemes. Given the relatively common genetic background of most European populations and similar health care systems, the reasons for the differences observed appear arbitrary and contrary to the optimal benefit of this important preventive health measure. Harmonization of disease screening panels, spectrum of metabolites analysed, sizes of screening laboratories, analytical procedures, follow-up management and proficiency and quality testing is urgently warranted on the European level. This will hopefully occur before screening by novel applications of tandem mass spectrometry for additional groups of disorders including lysosomal storage disorders and X-linked adrenoleukodystrophy are implemented.
 ...
PMID:Expanded newborn screening in Europe 2007. 1764 97