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Biotin requirements are lower in human Jurkat lymphoid cells but homeostatic mechanisms are similar to those of HepG2 liver cells.

ABSTRACT: The following proteins are candidates for maintaining biotin homeostasis in humans: the biotin transporters sodium-dependent multivitamin transporter (SMVT) and monocarboxylate transporter 1, the biotinyl-protein ligase holocarboxylase synthetase (HCS), and the lysine-epsilon-biotin hydrolase biotinidase. Liver cells are supplied through the portal vein with high levels of water-soluble vitamins compared with those of peripheral tissues. We hypothesized that the mechanisms of biotin homeostasis are qualitatively and quantitatively different in cells derived from human liver (HepG2 cells) and lymphoid tissues (Jurkat cells). Cells were cultured in biotin-defined media, representing deficient (D), normal (N), and supplemented (S) individuals. Biotinylation of carboxylases depended on biotin availability in both cell types, but HepG2 cells required 3 times more biotin than Jurkat cells to maintain normal levels of holocarboxylases. The expression of biotin transporters was less in both types in medium S compared with cells in media D and N; in contrast, the expression of HCS was higher in cells in medium S compared with the other cells. The abundance of 3-methylcrotonyl-CoA carboxylase mRNA was lower in cells in medium D than cells in media N and S. The enrichment of biotinylated histones was higher at the SMVT promoter 1 in HepG2 and Jurkat cells in medium S compared with the corresponding cells in media D and N, presumably repressing the SMVT gene. The mechanisms of biotin homeostasis are qualitatively similar but quantitatively different in HepG2 and Jurkat cells; HCS, histone biotinylation, and biotin transporters play a role in homeostasis in both.

SUBMITTER: Mall GK

PROVIDER: S-EPMC2869498 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Biotin requirements are lower in human Jurkat lymphoid cells but homeostatic mechanisms are similar to those of HepG2 liver cells.

Mall Gaganpreet Kaur GK Chew Yap Ching YC Zempleni Janos J

The Journal of nutrition 20100331 6

The following proteins are candidates for maintaining biotin homeostasis in humans: the biotin transporters sodium-dependent multivitamin transporter (SMVT) and monocarboxylate transporter 1, the biotinyl-protein ligase holocarboxylase synthetase (HCS), and the lysine-epsilon-biotin hydrolase biotinidase. Liver cells are supplied through the portal vein with high levels of water-soluble vitamins compared with those of peripheral tissues. We hypothesized that the mechanisms of biotin homeostasis ...[more]

PMID: 20357078

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Project description:BackgroundA large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy.ObjectiveIn this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency.MethodsWe used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography-tandem mass spectrometry.ResultsRelative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased by >8-fold.ConclusionsOur findings provide strong evidence that coexisting carnitine deficiency masks some indicators of biotin deficiency and support the potential importance of the ratios of acylcarnitines arising from the acyl-CoA substrates and products for biotin-dependent carboxylases in detecting the biotin deficiency that is masked by coexisting carnitine deficiency.

Dataset Information

Biotin requirements are lower in human Jurkat lymphoid cells but homeostatic mechanisms are similar to those of HepG2 liver cells.

Publications

Biotin requirements are lower in human Jurkat lymphoid cells but homeostatic mechanisms are similar to those of HepG2 liver cells.

Similar Datasets

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