ON THE MECHANISM OF L-ALLOISOLEUCINE FORMATION - STUDIES ON A HEALTHY SUBJECT AND IN FIBROBLASTS FROM NORMALS AND PATIENTS WITH MAPLE SYRUP URINE DISEASE

被引:22
作者
SCHADEWALDT, P
HAMMEN, HW
DALLEFESTE, C
WENDEL, U
机构
[1] UNIV DUSSELDORF,DIABET FORSCHUNGSINST,W-4000 DUSSELDORF 1,GERMANY
[2] UNIV DUSSELDORF,KINDERKLIN,W-4000 DUSSELDORF 1,GERMANY
关键词
D O I
10.1007/BF01799676
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
l-Alloisoleucine formation from l-isoleucine was studied in vitro and in vivo. When a healthy subject was loaded with l-isoleucine, plasma levels of l-isoleucine and 3-methyl-2-oxopentanoate (KMV), as well as l-alloisoleucine, increased. Peak values were reached successively and were in the order l-isoleucine > > KMV > >l-alloisoleucine. Metabolic clearance of l-isoleucine and KMV was rapid; clearance of l-alloisoleucine was considerably delayed. When human skin fibroblast cultures were challenged with l-isoleucine, KMV accumulated at a gradually decreased rate, whereas l-alloisoleucine accumulated at a gradually accelerated rate. KMV and l-alloisoleucine formation were related and depended on the l-isoleucine concentration applied. In cell lines derived from MSUD patients (classical form), metabolite formation was only about 2-fold higher than in control strains. The relatively small difference between normal and MSUD fibroblasts in vitro as opposed to the striking differences between healthy subjects and MSUD patients in vivo are discussed with respect to the significance of physiological mechanisms participating in the formation and degradation of l-alloisoleucine in man. © 1990 Society for the Study of Inborn Errors of Metabolism and Kluwer Academic Publishers.
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页码:137 / 150
页数:14
相关论文
共 29 条
[11]  
MEISTER A, 1951, J BIOL CHEM, V190, P269
[12]   NITROGEN SPARING INDUCED BY LEUCINE COMPARED WITH THAT INDUCED BY ITS KETO ANALOG, ALPHA-KETOISOCAPROATE, IN FASTING OBESE MAN [J].
MITCH, WE ;
WALSER, M ;
SAPIR, DG .
JOURNAL OF CLINICAL INVESTIGATION, 1981, 67 (02) :553-562
[13]  
SCHADEWALDT P, 1989, BIOL CHEM H-S, V370, P951
[14]   FUNCTIONAL DIFFERENCES IN THE CATABOLISM OF BRANCHED-CHAIN L-AMINO-ACIDS IN CULTURED NORMAL AND MAPLE SYRUP URINE DISEASE FIBROBLASTS [J].
SCHADEWALDT, P ;
WENDEL, U .
BIOCHEMICAL MEDICINE AND METABOLIC BIOLOGY, 1989, 41 (02) :105-116
[15]   TRANSAMINATION AND OXIDATIVE DECARBOXYLATION OF L-ISOLEUCINE, L-ALLOISOLEUCINE AND RELATED 2-OXO ACIDS IN PERFUSED RAT HIND-LIMB MUSCLE [J].
SCHADEWALDT, P ;
RADECK, W ;
HAMMEN, HW ;
STAIB, W .
BIOCHIMICA ET BIOPHYSICA ACTA, 1989, 992 (01) :115-123
[16]   ANALYSIS OF MAPLE SYRUP URINE DISEASE IN CELL-CULTURE - USE OF SUBSTRATES [J].
SCHADEWALDT, P ;
BECK, K ;
WENDEL, U .
CLINICA CHIMICA ACTA, 1989, 184 (01) :47-56
[17]   A CONVENIENT ENZYMATIC METHOD FOR THE DETERMINATION OF 4-METHYL-2-OXOPENTANOATE IN PLASMA - COMPARISON WITH HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ANALYSIS [J].
SCHADEWALDT, P ;
HUMMEL, W ;
TRAUTVETTER, U ;
WENDEL, U .
CLINICA CHIMICA ACTA, 1989, 183 (02) :171-182
[18]  
SCRIVER CR, 1965, PEDIATRICS, V36, P592
[19]   MAPLE SYRUP URINE DISEASE - BRANCHED-CHAIN AMINO-ACID CONCENTRATIONS AND METABOLISM IN CULTURED HUMAN LYMPHOBLASTS [J].
SKAPER, SD ;
MOLDEN, DP ;
SEEGMILLER, JE .
BIOCHEMICAL GENETICS, 1976, 14 (7-8) :527-539
[20]  
SNYDERMAN SE, 1964, PEDIATRICS, V34, P454