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Nutrient-Gene Expression

Biotin Uptake into Human Peripheral Blood Mononuclear Cells Increases Early in the Cell Cycle, Increasing Carboxylase Activities^{1 ,2}

J. Steven Stanley, Donald M. Mock^*, Jacob B. Griffin and Janos Zempleni^,**3

Arkansas Children’s Hospital Research Institute, Little Rock, AR; ^* Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR; Departments of Nutritional Science and Dietetics, and ^** Biochemistry, University of Nebraska at Lincoln, Lincoln, NE

³To whom correspondence and reprint requests should be addressed. E-mail: jzempleni2{at}unl.edu.

Cells respond to proliferation with increased accumulation of biotin, suggesting that proliferation enhances biotin demand. Here we determined whether peripheral blood mononuclear cells (PBMC) increase biotin uptake at specific phases of the cell cycle, and whether biotin is utilized to increase biotinylation of carboxylases. Biotin uptake was quantified in human PBMC that were arrested chemically at specific phases of the cell cycle, i.e., biotin uptake increased in the G1 phase of the cycle [658 ± 574 amol biotin/(10⁶ cells x 30 min)] and remained increased during phases S, G2, and M compared with quiescent controls [200 ± 62 amol biotin/(10⁶ cells x 30 min)]. The abundance of the sodium-dependent multivitamin transporter (SMVT, which transports biotin) was similar at all phases of the cell cycle, suggesting that transporters other than SMVT or splicing variants of SMVT may account for the increased biotin uptake observed in proliferating cells. Activities of biotin-dependent 3-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase were up to two times greater in proliferating PBMC compared with controls. The abundance of mRNA encoding 3-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase paralleled carboxylase activities, suggesting that PBMC respond to proliferation with increased expression of genes encoding carboxylases. Similarly, expression of the gene encoding holocarboxylase synthetase (which catalyzes binding of biotin to carboxylases) increased in response to proliferation, suggesting that cellular capacity to biotinylate carboxylases was increased. In summary, these findings suggest that PBMC respond to proliferation with increased biotin uptake early in the cell cycle, and that biotin is utilized to increase activities of two of the four biotin-requiring carboxylases.

KEY WORDS: • biotin • carboxylase • cell cycle • peripheral blood mononuclear cells • transport • humans

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				J. Zempleni, M. Gralla, G. Camporeale, and Y. I. Hassan Sodium-Dependent Multivitamin Transporter Gene Is Regulated at the Chromatin Level by Histone Biotinylation in Human Jurkat Lymphoblastoma Cells J. Nutr., January 1, 2009; 139(1): 163 - 166. [Abstract] [Full Text] [PDF]

				S. Wiedmann, J. D. Eudy, and J. Zempleni Biotin Supplementation Increases Expression of Genes Encoding Interferon-{gamma}, Interleukin-1{beta}, and 3-Methylcrotonyl-CoA Carboxylase, and Decreases Expression of the Gene Encoding Interleukin-4 in Human Peripheral Blood Mononuclear Cells J. Nutr., March 1, 2003; 133(3): 716 - 719. [Abstract] [Full Text] [PDF]