Marginal biotin deficiency is teratogenic.
Recent studies of biotin status during pregnancy provide evidence that a marginal degree of biotin develops in a substantial proportion of women during normal pregnancy. Several lines of evidence suggest that, although the degree of biotin deficiency is not severe enough to produce the classic cutaneous and behavioral manifestations of biotin deficiency, the deficiency is severe enough to produce metabolic derangements in women and that characteristic fetal malformations occur at a high rate in some mammals. Moreover, our analysis of data from a published multivitamin supplementation study provide significant albeit indirect evidence that the marginal degree of biotin deficiency that occurs spontaneously in normal human gestation is teratogenic. Investigation of potential mechanisms provides evidence that biotin transport by the human placenta is weak. Further, proliferating cells accumulate biotin at a rate five times faster than quiescent cells; this observation suggests that there is an increased biotin requirement associated with cell proliferation. Perhaps this requirement arises from the need to synthesize additional biotin-dependent holocarboxylases or provide additional biotin as a substrate for biotinylation of cellular histones. Reduced activity of the biotin-dependent enzymes acetyl-CoA carboxylase and propionyl-CoA carboxylase can cause alterations of lipid metabolism and might theoretically lead to alterations of polyunsaturated fatty acid and prostaglandin metabolism that derange normal skeletal development.
Zempleni
J
J
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, 72202, USA.
Mock
D M
DM
D000818:Animals; D001710:Biotin / Q000172:deficiency*; D000013:Congenital Abnormalities / Q000209:etiology* / Q000517:prevention & control; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D008322:Mammals; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D014815:Vitamins
D014815:Vitamins; D001710:Biotin