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Biochemical and Molecular Actions of Nutrients
Research Communication

3-Hydroxypropionic Acid and Methylcitric Acid Are Not Reliable Indicators of Marginal Biotin Deficiency in Humans¹

Donald M. Mock^*,,2, Cindy L. Henrich-Shell^*, Nadine Carnell^**, Phyllis Stumbo and Nell I. Mock^*

^* Departments of Biochemistry & Molecular Biology and Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205; ^** General Clinical Research Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205; and Clinical Research Center, University of Iowa College of Medicine, Iowa City, IA

²To whom correspondence should be addressed. E-mail: MockDonaldM{at}uams.edu.

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.

KEY WORDS: • organic acid • biotin deficiency • human • 3-hydroxypropionic acid • methylcitric acid

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