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

Oleh:

Bogusiewicz, Anna ; Horvath, Thomas D. ; Stratton, Shawna L. ; Mock, Donald M. ; Boysen, Gunnar

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: JN: The Journal of Nutrition vol. 142 no. 09 (Sep. 2012), page 1621-1625.
Topik: BIOCHEMICAL; Molecular; Genetic Mechanisms

Ketersediaan

Perpustakaan FK Nomor Panggil: J42.K.2012.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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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