title: 3-Hydroxypropionic acid and methylcitric acid are not reliable indicators of marginal biotin deficiency in humans.
abstract: In two studies comprising 10 and 11 subjects, respectively, marginal biotin deficiency was induced experimentally by an egg-white diet in healthy men and women. The following urinary organic acids were assessed for their usefulness in detecting marginal biotin status: 1) 3-hydroxypropionic acid and methylcitric acid, organic acids that reflect decreased activity of the biotin-dependent enzyme propionyl-CoA carboxylase and 2) methylcrotonylglycine and isovalerylglycine, organic acids that reflect decreased activity of methylcrotonyl-CoA carboxylase. Mean 3-hydroxypropionic acid excretion rates remained normal during biotin depletion in both studies. By the end of the depletion period, 3-hydroxypropionic acid excretion identified only 5 of 21 marginally deficient subjects. Mean methylcitric acid excretion increased (P < 0.0001) in the first study but not in the second. Mean methylcrotonylglycine excretion increased in each study (P < 0.004 and P < 0.05, respectively); methylcrotonylglycine excretion identified 13 of 21 marginally deficient subjects. Mean isovalerylglycine excretion increased only in the first study (P = 0.006) and identified only 6 of 21 deficient subjects. We conclude that none of these organic acids is as sensitive an indicator of marginal biotin deficiency as 3-hydroxyisovaleric acid, which reflects decreased methylcrotonyl-CoA carboxylase.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. MockDonaldM@uams.edu
authors.forename: Donald M
authors.initials: DM
authors.lastname: Mock
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Henrich-Shell
authors.forename: Nadine
authors.initials: N
authors.lastname: Carnell
authors.forename: Phyllis
authors.initials: P
authors.lastname: Stumbo
authors.forename: Nell I
authors.initials: NI
authors.lastname: Mock
mesh_terms: D001710:Biotin / Q000008:administration & dosage / Q000172:deficiency* / Q000652:urine; D019735:Carbon-Carbon Ligases / Q000378:metabolism / Q000652:urine; D002951:Citrates / Q000378:metabolism; D004032:Diet; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D019344:Lactic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D012016:Reference Values
chemical_list: D002951:Citrates; D019344:Lactic Acid; D001710:Biotin; C031601:hydracrylic acid; D019735:Carbon-Carbon Ligases; C021573:methylcrotonoyl-CoA carboxylase