Lymphocyte propionyl-CoA carboxylase and its activation by biotin are sensitive indicators of marginal biotin deficiency in humans

Stratton, Shawna L.; Bogusiewicz, Anna; Mock, Matthew M; Mock, Nell I.; Wells, Amanda M; Mock, Donald M.

doi:10.1093/ajcn/84.2.384

Cited by 27 publications

(30 citation statements)

References 21 publications

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“…Analyses were performed on urine samples obtained from participants in a study previously reported (4)(5)(6). The Institutional Review Board for the University of Arkansas for Medical Sciences approved this study.…”

Section: Participants and Methodsmentioning

confidence: 99%

Measurement of Acylcarnitine Substrate to Product Ratios Specific to Biotin-Dependent Carboxylases Offers a Combination of Indicators of Biotin Status in Humans

Bogusiewicz

Horvath

Stratton

et al. 2012

The Journal of Nutrition

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This work describes a novel liquid chromatography tandem MS (LC-MS/MS) method for the determination of ratios of acylcarnitines arising from acyl-CoA substrates and products that reflect metabolic disturbances caused by marginal biotin deficiency. The urinary ratios reflecting reduced activities of biotin-dependent enzymes include the following: 1) the ratio of 3-hydroxyisovalerylcarnitine : 3-methylglutarylcarnitine (3HIAc : MGc) for methylcrotonyl-CoA carboxylase; 2) the ratio of propionylcarnitine:methylmalonylcarnitine (Pc : MMc) for propionyl-CoA carboxylase (PCC); and 3) the ratio of acetylcarnitine : malonylcarnitine (Ac : Mc) for acetyl-CoA carboxylase. To demonstrate the suitability of the LC-MS/MS method for biomonitoring, we measured the 3 ratios for 7 healthy adults at various time points (d 0, 14, and 28) during the induction of marginal biotin through the consumption of egg white. The mean change in the Pc : MMc ratio relative to d 0 was 5.3-fold by d 14 (P = 0.0049) and 8.5-fold by d 28 (P = 0.0042). The mean change in the 3HIAc : MGc ratio was 2.8-fold by d 14 (P = 0.0022) and 3.8-fold by d 28 (P = 0.0001). The mean change in the Ac : Mc ratio was 2.9-fold by d 14 (P = 0.03) and 4.7-fold by d 28 (P = 0.02). The results suggest that simultaneous assessment of ratios of multiple biotin-dependent pathways offers insight into the complex metabolic disturbances caused by marginal biotin deficiency. We hypothesize that one or a combination of the ratios might be more sensitive or robust with respect to other nutrient deficiencies or confounding metabolic processes.

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Section: Participants and Methodsmentioning

confidence: 99%

Measurement of Acylcarnitine Substrate to Product Ratios Specific to Biotin-Dependent Carboxylases Offers a Combination of Indicators of Biotin Status in Humans

Bogusiewicz

Horvath

Stratton

et al. 2012

The Journal of Nutrition

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“…Urinary excretion of 3HIA and 3HIA-carnitine was also shown to significantly increase in response to an oral challenge of leucine, an amino acid whose degradation requires MCC (Mock et al, 2002a;Mock et al, 2011). A decrease in PCC activity in lymphocytes and, more recently, an increase in the ratios of acylcarnitines in urine, arising from acyl-CoA substrates and their products, which reflect disturbances in biotin-dependent carboxylase activities, were also observed in response to induced biotin insufficiency (Stratton et al, 2006;Bogusiewicz et al, 2012).…”

Section: Biomarkersmentioning

confidence: 99%

Scientific Opinion on Dietary Reference Values for biotin

Products¹

2014

EFS2

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Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for biotin. Biotin is a water-soluble vitamin which serves as a co-factor for several carboxylases that play critical roles in the synthesis of fatty acids, the catabolism of branched-chain amino acids and gluconeogenesis. Dietary biotin deficiency is rare. Data on biomarkers of biotin intake or status are insufficient to be used in determining the requirement for biotin. Data available on biotin intakes and health consequences are very limited and cannot be used for deriving DRVs for biotin. As there is insufficient evidence available to derive an Average Requirement and a Population Reference Intake, an Adequate Intake (AI) is proposed. The setting of AIs is based on observed biotin intakes with a mixed diet and the apparent absence of signs of deficiency in the EU, suggesting that current intake levels are adequate. The AI for adults is set at 40 µg/day. The AI for adults also applies to pregnant women. For lactating women, an additional 5 µg biotin/day over and above the AI for adults is proposed, to compensate for biotin losses through breast milk. For infants over six months, an AI of 6 µg/day is proposed by extrapolating from the biotin intake of exclusively breastfed infants aged zero to six months, using allometric scaling and reference body weight for each age group, in order to account for the role of biotin in energy metabolism. The AIs for children aged 1-3 and 4-10 years are set at 20 and 25 µg/day, respectively, and for adolescents at 35 µg/day, based on observed intakes in the EU. In 1993, the Scientific Committee for Food proposed an Acceptable Range of Intakes of biotin for adults of 15-100 µg/day, based on observed intakes of biotin in European countries, which were considered adequate to meet requirements and prevent deficiency. © European FoodBiotin is a water-soluble vitamin which serves as a co-factor for several carboxylases that play critical roles in the synthesis of fatty acids, the catabolism of branched-chain amino acids and gluconeogenesis. Dietary biotin deficiency is rare.Free biotin is absorbed nearly completely, while there is a lack of data on the absorption of proteinbound biotin from foods. In the cell, biotin is covalently attached to biotin-dependent carboxylases, from which it can be released by other enzymes, or, alternatively, is catabolised through different pathways. Biotin and its metabolites are excreted in the urine.The Panel notes that biomarkers sensitive to biotin depletion have been identified. These include urinary biotin excretion and biomarkers of biotin function, such as urinary excretion of 3-hydroxyisovaleric acid (3HIA) and 3HIA-carnitine, activity of propionyl-CoA carboxylase and abundance of biotinylated β-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase in lymphocytes. However, data from the general population are limited so that the variability characteristics of these biomarkers an...

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“…While the abundance of biotinylated proteins depends on biotin supply in adults (Chew et al 2008;Stratton et al 2006) and human cell cultures (Camporeale et al 2007a;Chew et al 2008;Gralla et al 2008;Pestinger et al 2011), human biotin requirements are still unknown (National 1998). Depletion of histone biotinylation causes deregulation of genes (Camporeale et al 2007b;Gralla et al 2008;Pestinger et al 2011).…”

Section: Biotinylation Of Histonesmentioning

confidence: 99%

Nutrition, Histone Epigenetic Marks, and Disease

Zempleni

Liu

Xue

2013

Environmental Epigenomics in Health and Disease

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The dietary intake of essential nutrients and bioactive food compounds is a process that occurs on a daily basis for the entire life span. Therefore, your diet has a great potential to cause changes in the epigenome. Known histone modifications include acetylation, methylation, biotinylation, poly(ADP-ribosylation), ubiquitination, and sumoylation. Some of these modifications depend directly on dietary nutrients. For other modifications, bioactive dietary compounds may alter the activities of enzymes that establish or remove histone marks, thereby altering the epigenome. This chapter provides an overview of diet-dependent epigenomic marks in histones and their links with human health.

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Lymphocyte propionyl-CoA carboxylase and its activation by biotin are sensitive indicators of marginal biotin deficiency in humans

Abstract: PCC activity is the most sensitive indicator of biotin status tested to date. In future pregnancy studies, the use of lymphocyte PCC activity data should prove valuable in the assessment of biotin status.

Cited by 27 publications

References 21 publications

Measurement of Acylcarnitine Substrate to Product Ratios Specific to Biotin-Dependent Carboxylases Offers a Combination of Indicators of Biotin Status in Humans

Measurement of Acylcarnitine Substrate to Product Ratios Specific to Biotin-Dependent Carboxylases Offers a Combination of Indicators of Biotin Status in Humans

Scientific Opinion on Dietary Reference Values for biotin

Nutrition, Histone Epigenetic Marks, and Disease

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