title: Measurement of acylcarnitine substrate to product ratios specific to biotin-dependent carboxylases offers a combination of indicators of biotin status in humans.
abstract: 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.
authors: Department of Biochemistry and Molecular Biology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: Anna
authors: A
authors: Bogusiewicz
authors: Thomas D
authors: TD
authors: Horvath
authors: Shawna L
authors: SL
authors: Stratton
authors: Donald M
authors: DM
authors: Mock
authors: Gunnar
authors: G
authors: Boysen
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D015415:Biomarkers / Q000652:urine; D001710:Biotin / Q000172:deficiency* / Q000652:urine; D019735:Carbon-Carbon Ligases / Q000378:metabolism; D019731:Carbon-Nitrogen Ligases / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives* / Q000032:analysis / Q000652:urine; D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D003677:Deficiency Diseases / Q000175:diagnosis / Q000652:urine*; D005977:Glutarates / Q000032:analysis / Q000652:urine; D006801:Humans; D043586:Methylmalonyl-CoA Decarboxylase / Q000378:metabolism; D015203:Reproducibility of Results; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards
chemical_list: C098116:3-hydroxyisovalerylcarnitine; D015415:Biomarkers; D005977:Glutarates; C116917:acylcarnitine; C048290:3-methylglutarylcarnitine; D001710:Biotin; D019731:Carbon-Nitrogen Ligases; C019791:biotin carboxylase; D019735:Carbon-Carbon Ligases; D000103:Acetyl-CoA Carboxylase; C022458:propionyl CoA carboxylase (ATP-hydrolyzing); C021573:methylcrotonoyl-CoA carboxylase; D043586:Methylmalonyl-CoA Decarboxylase; D002331:Carnitine