Functional and metabolic implications of biotin deficiency for the rat heart.
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.
Velázquez-Arellano
Antonio
A
Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico.
Hernández-Esquivel
María de la Luz
Mde L
Sánchez
Rafael Moreno
RM
Ortega-Cuellar
Daniel
D
Rodríguez-Fuentes
Nayeli
N
Cano
Saúl
S
León-Del-Río
Alfonso
A
Carvajal
Karla
K
D000818:Animals; D001710:Biotin / Q000172:deficiency*; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D043586:Methylmalonyl-CoA Decarboxylase / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D011766:Pyruvate Carboxylase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D001710:Biotin; D011766:Pyruvate Carboxylase; D043586:Methylmalonyl-CoA Decarboxylase