Oral L-alloisoleucine loading studies in healthy subjects and in patients with maple syrup urine disease.
Total body and renal elimination of L-alloisoleucine was assessed after oral loads (0.57 mmol/kg body wt) in four healthy subjects and in five patients with maple syrup urine disease (MSUD) of different degrees of severity. As judged from the fictive initial concentration, L-alloisoleucine is distributed evenly in the total body water space. In the controls, estimated half-time of total elimination was 9.2 +/- 2.2 h (n = 4). In the MSUD patients, it ranged from 26 h (mild variant) to about 8 d (classical type). Because of its low renal clearance rate, L-alloisoleucine was cleared through ketomethylvalerate to greater than 99% in normals and to at least 73% in the MSUD patients. Assuming small variation in the losses of ketomethylvalerate through L-isoleucine formation and through renal excretion, this test allows ranking of MSUD patients with regard to their residual in vivo branched-chain oxo-acid dehydrogenase activity.
Schadewaldt
P
P
Institut für Physiologische Chemie II, Universität Düsseldorf, Germany.
Dalle-Feste
C
C
Langenbeck
U
U
Wendel
U
U
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000284:Administration, Oral; D000293:Adolescent; D002648:Child; D005260:Female; D006207:Half-Life; D006801:Humans; D007532:Isoleucine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007651:Keto Acids / Q000378:metabolism; D007658:Ketone Oxidoreductases / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008375:Maple Syrup Urine Disease / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D014018:Tissue Distribution
D007651:Keto Acids; D009097:Multienzyme Complexes; D007532:Isoleucine; C016211:alpha-keto-beta-methylvaleric acid; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)