In vivo enzyme activity in inborn errors of metabolism

Journal Article · Wed Aug 01 04:00:00 EDT 1990 · Metabolism, Clinical and Experimental; (USA)

DOI:https://doi.org/10.1016/0026-0495(90)90122-S· OSTI ID:6530071

Thompson, G N; Walter, J H; Leonard, J V; Halliday, D ^[1]

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1. Clinical Research Centre, Harrow (England)

Low-dose continuous infusions of (2H5)phenylalanine, (1-13C)propionate, and (1-13C)leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.

• OSTI ID: 6530071
• Journal Information: Metabolism, Clinical and Experimental; (USA), Journal Name: Metabolism, Clinical and Experimental; (USA) Vol. 39:8; ISSN METAA; ISSN 0026-0495
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
BIOLOGICAL PATHWAYS
CARBON 13
CARBON ISOTOPES
CARBOXYLIC ACIDS
DATA COVARIANCES
DEUTERIUM
DISEASES
ENZYME ACTIVITY
EVEN-ODD NUCLEI
HYDROGEN ISOTOPES
HYDROXY ACIDS
IN VIVO
ISOTOPE APPLICATIONS
ISOTOPE DILUTION
ISOTOPES
LEUCINE
LIGHT NUCLEI
MAMMALS
MAN
METABOLISM
MONOCARBOXYLIC ACIDS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHENYLALANINE
PRIMATES
PROPIONIC ACID
STABLE ISOTOPES
TRACER TECHNIQUES
TYROSINE
UROGENITAL SYSTEM DISEASES
VERTEBRATES