Biotin starvation with adequate glucose provision causes paradoxical changes in fuel metabolism gene expression similar in rat (Rattus norvegicus), nematode (Caenorhabditis elegans) and yeast (Saccharomyces cerevisiae).
OBJECTIVE
Biotin affects the genetic expression of several glucose metabolism enzymes, besides being a cofactor of carboxylases. To explore how extensively biotin affects the expression of carbon metabolism genes, we studied the effects of biotin starvation and replenishment in 3 distantly related eukaryotes: yeast Saccharomyces cerevisiae, nematode Caenorhabditis elegans and rat Rattus norvegicus.


METHODS
Biotin starvation was produced in Wistar rats, in C. elegans N2 and S. cerevisiae W303A fed with abundant glucose. High-density oligonucleotide microarrays were used to find gene expression changes. Glucose consumption, lactate and ethanol were measured by conventional tests.


RESULTS
In spite of abundant glucose provision, the expression of fatty oxidation and gluconeogenic genes was augmented, and the transcripts for glucose utilization and lipogenesis were diminished in biotin starvation. These results were associated with diminished glucose consumption and glycolysis products (lactate and ethanol in yeast), which was consistent across 3 very different eukaryotes.


CONCLUSIONS
The results point toward a strongly selected role of biotin in the control of carbon metabolism, and in adaptations to variable availability of carbon, conceivably mediated by signal transduction including soluble guanylate cyclase, cGMP and a cGMP-dependent protein kinase (PKG) and/or biotin-dependent processes.
Ortega-Cuellar
D
D
Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas UNAM, México, México.
Hernandez-Mendoza
A
A
Moreno-Arriola
E
E
Carvajal-Aguilera
K
K
Perez-Vazquez
V
V
Gonzalez-Alvarez
R
R
Velazquez-Arellano
A
A
D000818:Animals; D001710:Biotin / Q000172:deficiency*; D017173:Caenorhabditis elegans / Q000235:genetics*; D002952:Citric Acid Cycle; D005947:Glucose / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D014158:Transcription, Genetic
D001710:Biotin; D005947:Glucose