Low expression of long-chain acyl-CoA dehydrogenase in human skeletal muscle.
OBJECTIVE
Long-chain acyl-CoA dehydrogenase (LCAD) is a mitochondrial flavoenzyme thought to be one of the major enzymes responsible for the first step of long-chain fatty acid (LCFA) beta-oxidation. Surprisingly, recent studies have shown LCAD is hardly detectable in human tissues such as liver and heart. Skeletal muscle is the largest organ in the body in terms of mass, and accounts for the majority of LCFA oxidation, especially during exercise. The purpose of this study was to investigate the expression levels of LCAD in human skeletal muscle.


METHODS
Muscle biopsies were obtained from the vastus lateralis of healthy athletic men and women, and examined for mRNA abundance, protein content, and enzyme activity of LCAD. We compared LCAD content with that of very-long chain acyl-CoA dehydrogenase (VLCAD) and medium chain acyl-CoA dehydrogenase (MCAD); two mitochondrial beta-oxidation enzymes that have overlapping chain-length specificity to that of LCAD. LCAD protein content and enzyme activity were also examined in enriched mitochondrial protein fractions. As controls, LCAD presence in skeletal muscle was compared to human heart, liver, and mouse skeletal muscle.


RESULTS
The mRNA presence of LCAD in human skeletal muscle is significantly less than VLCAD and MCAD (0.08+/-0.01 vs 7.3+/-0.5 vs 2.4+/-0.2 respectively, P<or=0.0001). LCAD protein was undetectable in human muscle homogenates, and coordinately LCAD enzyme activity was undetectable in enriched mitochondrial samples.


CONCLUSIONS
LCAD is minimally expressed in human skeletal muscle and likely does not play a significant role in LCFA oxidation.
Maher
Amy C
AC
Department of Medical Science, McMaster University, Ontario, Canada. maherac@mcmaster.ca
Mohsen
Al-Walid
AW
Vockley
Jerry
J
Tarnopolsky
Mark A
MA
D042964:Acyl-CoA Dehydrogenase / Q000235:genetics; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000235:genetics*; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008929:Mitochondria, Heart / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D008931:Mitochondria, Muscle / Q000201:enzymology; D018482:Muscle, Skeletal / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult
D012333:RNA, Messenger; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain