Document Detail


Identification and characterization of new long chain acyl-CoA dehydrogenases.
MedLine Citation:
PMID:  21237683     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Long-chain fatty acids are an important source of energy in muscle and heart where the acyl-CoA dehydrogenases (ACADs) participate in consecutive cycles of β-oxidation to generate acetyl-CoA and reducing equivalents for generating energy. However, the role of long-chain fatty acid oxidation in the brain and other tissues that do not rely on fat for energy is poorly understood. Here we characterize two new ACADs, ACAD10 and ACAD11, both with significant expression in human brain. ACAD11 utilizes substrates with primary carbon chain lengths between 20 and 26, with optimal activity towards C22CoA. The combination of ACAD11 with the newly characterized ACAD9 accommodates the full spectrum of long chain fatty acid substrates presented to mitochondrial β-oxidation in human cerebellum. ACAD10 has significant activity towards the branched-chain substrates R and S, 2 methyl-C15-CoA and is highly expressed in fetal but not adult brain. This pattern of expression is similar to that of LCAD, another ACAD previously shown to be involved in long branched chain fatty acid metabolism. Interestingly, the ACADs in human cerebellum were found to have restricted cellular distribution. ACAD9 was most highly expressed in the granular layer, ACAD11 in the white matter, and MCAD in the molecular layer and axons of specific neurons. This compartmentalization of ACADs in the human central nerve system suggests that β-oxidation in cerebellum participates in different functions other than generating energy, for example, the synthesis and/or degradation of unique cellular lipids and catabolism of aromatic amino acids, compounds that are vital to neuronal function.
Authors:
Miao He; Zhengtong Pei; Al-Walid Mohsen; Paul Watkins; Geoffrey Murdoch; Paul P Van Veldhoven; Regina Ensenauer; Jerry Vockley
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-12-17
Journal Detail:
Title:  Molecular genetics and metabolism     Volume:  102     ISSN:  1096-7206     ISO Abbreviation:  Mol. Genet. Metab.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-15     Completed Date:  2011-07-05     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  9805456     Medline TA:  Mol Genet Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  418-29     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Acyl-CoA Dehydrogenase / chemistry,  genetics,  metabolism*
Acyl-CoA Dehydrogenase, Long-Chain / chemistry,  genetics,  metabolism*
Alternative Splicing
Amino Acid Sequence
Brain / embryology,  growth & development,  metabolism*
Cells, Cultured
Cerebellum / anatomy & histology,  cytology,  metabolism
Computer Simulation
Enzyme Assays
Gene Components
Humans
Isoenzymes / metabolism
Kidney / metabolism
Mitochondria / metabolism
Molecular Sequence Data
Muscle, Skeletal / metabolism
Organ Specificity
Protein Structure, Tertiary
RNA, Messenger / genetics,  metabolism
Recombinant Proteins / biosynthesis,  chemistry
Sequence Alignment
Substrate Specificity
Transcription, Genetic
Grant Support
ID/Acronym/Agency:
DK78755/DK/NIDDK NIH HHS; R01 DK054936/DK/NIDDK NIH HHS; R01 DK054936-10/DK/NIDDK NIH HHS; R01 DK078775/DK/NIDDK NIH HHS; R01 DK078775-04/DK/NIDDK NIH HHS; R01 DK54936/DK/NIDDK NIH HHS; UL1 RR024153/RR/NCRR NIH HHS; UL1 TR000005/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Isoenzymes; 0/RNA, Messenger; 0/Recombinant Proteins; EC 1.3.8.7/Acyl-CoA Dehydrogenase; EC 1.3.8.8/Acyl-CoA Dehydrogenase, Long-Chain; EC 1.3.99.3/ACAD10 protein, human
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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