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Evidence of a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity in red skeletal muscle.
Am J Physiol Endocrinol Metab. 2002 May; 282(5):E1014-22.AJ

Abstract

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.

Authors+Show Affiliations

Department of Biochemistry, East Carolina University, Greenville, North Carolina 27858, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11934665

Citation

Kim, Jong-Yeon, et al. "Evidence of a malonyl-CoA-insensitive Carnitine Palmitoyltransferase I Activity in Red Skeletal Muscle." American Journal of Physiology. Endocrinology and Metabolism, vol. 282, no. 5, 2002, pp. E1014-22.
Kim JY, Koves TR, Yu GS, et al. Evidence of a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity in red skeletal muscle. Am J Physiol Endocrinol Metab. 2002;282(5):E1014-22.
Kim, J. Y., Koves, T. R., Yu, G. S., Gulick, T., Cortright, R. N., Dohm, G. L., & Muoio, D. M. (2002). Evidence of a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity in red skeletal muscle. American Journal of Physiology. Endocrinology and Metabolism, 282(5), E1014-22.
Kim JY, et al. Evidence of a malonyl-CoA-insensitive Carnitine Palmitoyltransferase I Activity in Red Skeletal Muscle. Am J Physiol Endocrinol Metab. 2002;282(5):E1014-22. PubMed PMID: 11934665.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence of a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity in red skeletal muscle. AU - Kim,Jong-Yeon, AU - Koves,Timothy R, AU - Yu,Geng-Sheng, AU - Gulick,Tod, AU - Cortright,Ronald N, AU - Dohm,G Lynis, AU - Muoio,Deborah M, PY - 2002/4/6/pubmed PY - 2002/5/17/medline PY - 2002/4/6/entrez SP - E1014 EP - 22 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 282 IS - 5 N2 - 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. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/11934665/Evidence_of_a_malonyl_CoA_insensitive_carnitine_palmitoyltransferase_I_activity_in_red_skeletal_muscle_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00233.2001?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -