Endogenous catabolism is the major source of toxic metabolites in isovaleric acidemia.
A patient with isovaleryl-coenzyme A dehydrogenase deficiency was given a synthetic oral feed containing L-(2H3-methyl)-leucine of high isotopic purity as the only dietary precursor to the defective enzyme. Metabolites derived from this source were readily distinguished from their unlabeled endogenous counterparts by mass spectrometry. During 6 consecutive days of labeled leucine ingestion, the average daily excretion of labeled metabolites was only about 10% of the total derived from leucine. It is suggested that therapy should be directed toward the control of endogenous protein turnover rather than the restriction of dietary protein intake.
D000592:Amino Acid Metabolism, Inborn Errors / Q000178:diet therapy / Q000378:metabolism*; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D004044:Dietary Proteins / Q000008:administration & dosage / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D050769:Isovaleryl-CoA Dehydrogenase; D007930:Leucine / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D010088:Oxidoreductases / Q000172:deficiency*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D014631:Valerates / Q000378:metabolism
D004044:Dietary Proteins; D014631:Valerates; C005916:N-isovalerylglycine; C027333:3-methylbutyrylcarnitine; C004961:beta-hydroxyisovaleric acid; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050769:Isovaleryl-CoA Dehydrogenase; D007930:Leucine; D002331:Carnitine; D005998:Glycine