Functional and metabolic implications of biotin deficiency for the rat heart
Por:
Velázquez-Arellano A., Hernandez-Esquivel, MD, Sánchez R.M., Ortega-Cuellar D., Rodríguez-Fuentes N., Cano S., León-Del-Río A., Carvajal K.
Publicada:
1 dic 2008
Resumen:
The tricarboxylic acid (TCA) cycle is the main ATP provider for the heart. TCA carbons must be replenished by anaplerosis for normal cardiac function. Biotin is cofactor of the anaplerotic enzymes pyruvate and propionyl-CoA carboxylases. Here, we found that in biotin deficient rats, both carboxylases decreased 90% in adipose tissue, jejunum and spleen, but in heart they conserved about 60% residual activity. We then investigated if under biotin deficiency (BtDEF), the heart is able to maintain its function in vivo and in isolated conditions, and during ischemia and reperfusion, where metabolism drastically shifts from oxidative to mainly glycolytic. Neither glucose nor octanoate oxidation were severely affected in BtDEF hearts, as assessed by mechanical performance, oxygen uptake or high-energy metabolite content; however, myocardial hexokinase activity and lactate concentration were reduced in deficient hearts. When challenged by ischemia and reperfusion injury, BtDEF hearts did not suffer more damage than the controls, although they lowered significantly their performance, when changed to ischemic conditions, which may have clinical implications. Post-ischemic increase in ADP/ATP ratio was similar in both groups, but during reperfusion there was higher rhythm perturbation in BtDEF hearts. By being relatively insensitive to biotin deficiency, cardiac tissue seems to be able to replenish TCA cycle intermediates and to maintain ATP synthesis. © 2008 Elsevier Inc. All rights reserved.
Filiaciones:
Velázquez-Arellano A.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Unidad Genet Nutr, Mexico City 04510, DF, Mexico
Sánchez R.M.:
Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, Mexico
Ortega-Cuellar D.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Unidad Genet Nutr, Mexico City 04510, DF, Mexico
Rodríguez-Fuentes N.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Unidad Genet Nutr, Mexico City 04510, DF, Mexico
Cano S.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Unidad Genet Nutr, Mexico City 04510, DF, Mexico
León-Del-Río A.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Biol Mol & Biotecnol, Mexico City 04510, DF, Mexico
Carvajal K.:
Laboratorio de Bioquímica Genética, Torre de Investigación, Instituto Nacional de Pediatría, Av. Del IMAN # 1, Col. Insurgentes Cuicuilco, 04530 Mexico DF, Mexico
Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, Mexico
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