| Measurement of acylcarnitine substrate to product ratios specific to biotin-dependent carboxylases offers a combination of indicators of biotin status in humans. | |
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MedLine Citation:
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PMID: 22833654 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Anna Bogusiewicz; Thomas D Horvath; Shawna L Stratton; Donald M Mock; Gunnar Boysen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-07-25 |
Journal Detail:
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Title: The Journal of nutrition Volume: 142 ISSN: 1541-6100 ISO Abbreviation: J. Nutr. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-08-22 Completed Date: 2012-10-30 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0404243 Medline TA: J Nutr Country: United States |
Other Details:
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Languages: eng Pagination: 1621-5 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetyl-CoA Carboxylase
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metabolism Biological Markers / urine Biotin / deficiency*, urine Carbon-Carbon Ligases / metabolism Carbon-Nitrogen Ligases / metabolism Carnitine / analogs & derivatives*, analysis, urine Chromatography, Liquid / methods*, standards Deficiency Diseases / diagnosis, urine* Glutarates / analysis, urine Humans Methylmalonyl-CoA Decarboxylase / metabolism Reproducibility of Results Substrate Specificity Tandem Mass Spectrometry / methods*, standards |
| Grant Support | |
ID/Acronym/Agency:
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R01DK079892/DK/NIDDK NIH HHS; R01DK079892-26S1/DK/NIDDK NIH HHS; R37DDK36823//PHS HHS; R37DDK36823-26S1//PHS HHS; UL1 RR029884/RR/NCRR NIH HHS; UL1RR029884/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/3-hydroxyisovalerylcarnitine; 0/Biological Markers; 0/Glutarates; 0/acylcarnitine; 102673-95-0/3-methylglutarylcarnitine; 541-15-1/Carnitine; 58-85-5/Biotin; EC 4.1.1.41/Methylmalonyl-CoA Decarboxylase; EC 6.3.-/Carbon-Nitrogen Ligases; EC 6.3.4.14/biotin carboxylase; EC 6.4.-/Carbon-Carbon Ligases; EC 6.4.1.2/Acetyl-CoA Carboxylase; EC 6.4.1.3/propionyl CoA carboxylase (ATP-hydrolyzing); EC 6.4.1.4/methylcrotonoyl-CoA carboxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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