Contribution of odd-chain fatty acid oxidation to propionate production in disorders of propionate metabolism.
Whole-body propionate and protein kinetics and energy substrate metabolism were studied in five metronidazole-treated patients with propionic or methylmalonic acidemias by the use of a primed, 4-h constant infusion of [1-13C]propionate and L-[O-2H5]phenylalanine combined with indirect calorimetry. Measurements were performed during fasting and carbohydrate feeding, successively, to assess the contribution of odd-chain fatty acid oxidation to total propionate production. Fat oxidation decreased from 490 +/- 179 to 57 +/- 49 mumol.kg-1.h-1 (P < 0.05) as a result of feeding. Propionate appearance rate was 38.6 +/- 8 mumol.kg-1.h-1 during fasting and decreased to 22.6 +/- 5 mumol.kg-1.h-1 (P < 0.05) on the carbohydrate diet. Precursor amino acid catabolism did not change significantly (22 +/- 5 vs 21.2 +/- 5 mumol.kg-1.h-1), suggesting that the 41% reduction in propionate production observed in response to feeding was related to the suppression of fatty acid oxidation. Therefore, significant therapeutic gains may be expected from the use of diets aimed at reducing lipid oxidation.
Sbaï
D
D
Département de Physiologie, Hôpital des Enfants Malades, Paris, France.
Narcy
C
C
Thompson
G N
GN
Mariotti
A
A
Poggi
F
F
Saudubray
J M
JM
Bresson
J L
JL
D000293:Adolescent; D002153:Calorimetry, Indirect; D002648:Child; D002675:Child, Preschool; D005215:Fasting / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction; D010649:Phenylalanine / Q000378:metabolism; D011422:Propionates / Q000378:metabolism*
D005227:Fatty Acids; D011422:Propionates; D010649:Phenylalanine