Lactic acidosis in long-chain fatty acid beta-oxidation disorders.
Among the many disorders of fatty acid beta-oxidation known today, the disorders of long-chain fatty acid oxidation are the most severe and life-threatening. One remarkable abnormality, not observed in, for instance, medium-chain acyl-CoA dehydrogenase deficiency, is the moderate to severe lactic acidaemia in long-chain fatty acid beta-oxidation-deficient patients, suggesting that oxidation of pyruvate is also compromised. In order to understand the underlying basis of the lactic acidaemia in these patients, we have studied the formation of L-lactate and pyruvate in cultured skin fibroblasts incubated with D-glucose. All long-chain fatty acid beta-oxidation-deficient cell lines studied were found to show a moderate elevation of lactate when compared with control and medium-chain acyl-CoA dehydrogenase-deficient fibroblasts. Interestingly, differences were found between cells deficient in long-chain 3-hydroxyacyl-CoA dehydrogenase and very-long-chain acyl-CoA dehydrogenase, suggesting that saturated acyl-CoA esters and their 3-hydroxyacyl-CoA derivatives affect pyruvate metabolism differently.
Department of Clinical Chemistry, Academic Medical Centre, Amsterdam, The Netherlands.
F V
FV
Ventura
J P
JP
Ruiter
L
L
IJlst
I T
IT
de Almeida
R J
RJ
Wanders
D000140:Acidosis, Lactic / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007773:Lactates / Q000378:metabolism; D010084:Oxidation-Reduction; D018901:Peroxisomal Disorders / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011773:Pyruvates / Q000378:metabolism
D005227:Fatty Acids; D007773:Lactates; D011773:Pyruvates; D005947:Glucose