title: Biotin deficiency in rats: disturbances of leucine metabolism are detectable early.
abstract: 3-Methylcrotonyl-CoA originates from catabolism of leucine and is normally metabolized to acetyl-CoA. However, in biotin deficiency, reduced hepatic activity of the biotin-dependent enzyme methylcrotonyl-CoA carboxylase causes the enzyme's substrate 3-methylcrotonyl-CoA to be shunted via an alternate pathway to 3-hydroxyisovaleric acid (3-HIA), which is excreted at increased rates in the urine. In a previous study, unequivocal separation in 3-HIA excretion rates between biotin-deficient and control animals was not apparent until d 35 of feeding a diet that induced biotin deficiency. The present study tested the hypothesis that abnormal 3-HIA excretion could be detected earlier in the course of biotin deficiency if 3-HIA were more accurately measured using a method that incorporated an improved extraction regimen, deuterated 3-HIA as internal standard, and unlabeled 3-HIA as external standard. Biotin deficiency was induced in rats by feeding a diet containing avidin; control rats received the same diet and biotin injections. With the more accurate method, unequivocal detection of deficiency was possible in all deficient rats by d 16. This study provides evidence that, in rats, reduction of analytical error allows earlier detection of biotin deficiency and that disturbances of leucine metabolism occur earlier than previously appreciated.
authors.affiliation: Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242.
authors.forename: N I
authors.initials: NI
authors.lastname: Mock
authors.forename: D M
authors.initials: DM
authors.lastname: Mock
mesh_terms: D000818:Animals; D001710:Biotin / Q000097:blood / Q000172:deficiency*; D008401:Gas Chromatography-Mass Spectrometry; D007930:Leucine / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014631:Valerates / Q000652:urine
chemical_list: D014631:Valerates; C004961:beta-hydroxyisovaleric acid; D001710:Biotin; D007930:Leucine