Disease relevance of Acadl

• Long-chain acyl-CoA dehydrogenase (LCAD) deficiency is a disorder of mitochondrial fatty acid oxidation that is characterized by hypoglycemia, muscle weakness, and hepato- and cardiomegaly [1].
• We characterized the human LCAD gene structure and used in vitro transfection into cardiomyocytes and hepatoma cells of LCAD genomic fragments fused to a reporter gene to examine the effects of putative regulatory elements on transcription [2].

High impact information on Acadl

• A kinetic study of long-chain acyl-CoA dehydrogenase (LCAD) and very long-chain acyl-CoA dehydrogenase revealed that 5-trans-tetradecenoyl-CoA is a poorer substrate of LCAD than is 5-cis-tetradecenoyl-CoA, while both unsaturated acyl-CoAs are poor substrates of very long-chain acyl-CoA dehydrogenase when compared with myristoyl-CoA [3].
• cDNAs encoding the entire coding regions of the precursors (p) of rat long chain acyl-CoA (LCAD), short chain acyl-CoA (SCAD) and isovaleryl-CoA dehydrogenase (IVD) have been cloned and sequenced [4].
• The uniform nature of variant LCAD suggests that only a single, or at most a few, prevalent point mutations may be found in the majority of LCAD-deficient patients [1].
• The observed substrate specificities of long-chain acyl-CoA dehydrogenase (LCAD) and very-long-chain acyl-CoA dehydrogenase prompt the suggestion that LCAD is a functional component of the long-chain-specific beta-oxidation system [5].
• The catalytic efficiency of rat VLCAD with 14:1 as substrate was only 4% of the efficiency determined with tetradecanoyl-CoA, whereas LCAD acted equally well on both substrates [6].

Biological context of Acadl

• To discern whether two related nuclear genes are expressed similarly, the tissue distribution and developmental profile of the rat long- and medium-chain acyl-CoA dehydrogenase (LCAD and MCAD) mRNAs were compared [7].
• Our objective was to define regulatory elements of the human LCAD gene required for high levels of expression in mature heart and to locate elements suppressing gene expression in the fetus [2].
• The 200 bp of the human LCAD gene immediately upstream of the transcription initiation site are sufficient to act as a minimal promoter for the gene and provide some tissue-specific positive regulatory elements [2].
• Further results establish that switching pups from a low- to a high-fat diet for only 1 day was sufficient to induce large increases in cortical LCAD, MCAD, and ACO mRNA levels, and gavage experiments show that this upregulation of beta-oxidation gene expression is initiated within 6 h following lipid ingestion [8].

Anatomical context of Acadl

• LCAD and MCAD mRNAs were expressed in aorta, heart, and brown fat at levels 8-40 fold greater than in liver, kidney, and duodenum [7].

Associations of Acadl with chemical compounds

• The position of the catalytic glutamate, identified as Glu376 in porcine medium chain acyl-CoA dehydrogenase (MCAD), Glu254 in human isovaleryl-CoA dehydrogenase (IVD), and Glu261 in human long chain acyl-CoA dehydrogenase (LCAD), has been suggested to affect substrate chain length specificity [9].
• The CoA thioesters of docosahexaenoic acid, arachidonic acid, 4,7,10-cis-hexadecatrienoic acid, 5-cis-tetradecenoic acid, and 4-cis-decenoic acid were effectively dehydrogenated by both rat and human long-chain acyl-CoA dehydrogenases (LCAD), whereas they were poor substrates of very long-chain acyl-CoA dehydrogenases (VLCAD) [6].

Other interactions of Acadl

• Differential expression of LCAD and MCAD mRNAs reflects not only inherent gene prescribed programs, but also external influences such as hormones and diet [7].

Analytical, diagnostic and therapeutic context of Acadl

• Western blots of adult tissues with anti-rat LCAD antiserum showed corresponding amounts of LCAD protein subunits [7].

References