RGD Reference Report - Evidence of a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity in red skeletal muscle. - Rat Genome Database

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Evidence of a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity in red skeletal muscle.

Authors: Kim, JY  Koves, TR  Yu, GS  Gulick, T  Cortright, RN  Dohm, GL  Muoio, DM 
Citation: Kim JY, etal., Am J Physiol Endocrinol Metab 2002 May;282(5):E1014-22.
RGD ID: 628369
Pubmed: PMID:11934665   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpendo.00233.2001   (Journal Full-text)

Carnitine palmitoyltransferase I (CPT I), which is expressed as two distinct isoforms in liver (alpha) and muscle (beta), catalyzes the rate-limiting step in the transport of fatty acid into the mitochondria. Malonyl-CoA, a potent inhibitor of CPT I, is considered a key regulator of fatty acid oxidation in both tissues. Still unanswered is how muscle beta-oxidation proceeds despite malonyl-CoA concentrations that exceed the IC(50) for CPT Ibeta. We evaluated malonyl-CoA-suppressible [(14)C]palmitate oxidation and CPT I activity in homogenates of red (RG) and white (WG) gastrocnemius, soleus (SOL), and extensor digitorum longus (EDL) muscles. Adding 10 microM malonyl-CoA inhibited palmitate oxidation by 29, 39, 60, and 89% in RG, SOL, EDL, and WG, respectively. Thus malonyl-CoA resistance, which correlated strongly (0.678) with absolute oxidation rates (RG > SOL > EDL > WG), was greater in red than in white muscles. Similarly, malonyl-CoA-resistant palmitate oxidation and CPT I activity were greater in mitochondria from RG compared with WG. Ribonuclease protection assays were performed to evaluate whether our data might be explained by differential expression of CPT I splice variants. We detected the presence of two CPT Ibeta splice variants that were more abundant in red compared with white muscle, but the relative expression of the two mRNA species was unrelated to malonyl-CoA resistance. These results provide evidence of a malonyl-CoA-insensitive CPT I activity in red muscle, suggesting fiber type-specific expression of distinct CPT I isoforms and/or posttranslational modulations that have yet to be elucidated.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
fatty acid transport  TAS 628369; 628369; 628369 RGD 
long-chain fatty acid transport  IDA 628369 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
carnitine O-palmitoyltransferase activity  IDA 628369; 628369; 628369; 628369 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cpt1b  (carnitine palmitoyltransferase 1B)
Cpt1b_v1  (carnitine palmitoyltransferase 1B, variant 1)
Cpt1b_v2  (carnitine palmitoyltransferase 1B, variant 2)
Cpt1b_v3  (carnitine palmitoyltransferase 1B, variant 3)


Additional Information