Document Detail


Measurement of acylcarnitine substrate to product ratios specific to biotin-dependent carboxylases offers a combination of indicators of biotin status in humans.
MedLine Citation:
PMID:  22833654     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Anna Bogusiewicz; Thomas D Horvath; Shawna L Stratton; Donald M Mock; Gunnar Boysen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-25
Journal Detail:
Title:  The Journal of nutrition     Volume:  142     ISSN:  1541-6100     ISO Abbreviation:  J. Nutr.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-22     Completed Date:  2012-10-30     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  0404243     Medline TA:  J Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1621-5     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetyl-CoA Carboxylase / 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:
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:
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
Comments/Corrections

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