Intermediates of unsaturated fatty acid oxidation are incorporated in triglycerides but not in phospholipids in tissues from patients with mitochondrial beta-oxidation defects.
The fatty acid composition was determined of liver, skeletal muscle and heart obtained post mortem from patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD), multiple acyl-CoA dehydrogenase deficiency (MADD) and very long-chain acyl-CoA dehydrogenase deficiency (VLCADD). Increased amounts of 4-decenoic acid 10:1(n-6), 5-dodecenoic acid 12:1(n-7), 5-tetradecenoic acid 14:1(n-9), 5,8-tetradecadienoic acid 14:2(n-6) and 7,10-hexadecadienoic acid 16:2(n-6)--intermediates of unsaturated fatty acid oxidation--were found. Fractionation into different lipid classes showed that these fatty acids were exclusively present in the triglyceride fraction. They could not be detected in the free fatty acid fraction or in the phospholipid fraction. Our results suggest that intermediates of unsaturated fatty acid oxidation that accumulate as a consequence of MCADD, MADD and VLCADD are transported to the endoplasmic reticulum for esterification into neutral glycerolipids. The pattern of accumulation is characteristic for each disease, which makes fatty acid analysis of total lipid of post-mortem tissues a useful tool in the detection of mitochondrial fatty acid oxidation defects in patients who died unexpected, for example with sudden infant death syndrome.
Onkenhout
W
W
Department of Pediatrics, Leiden University Medical Center, The Netherlands.
Venizelos
V
V
Scholte
H R
HR
De Klerk
J B
JB
Poorthuis
B J
BJ
D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004951:Esterification; D017809:Fatal Outcome; D005231:Fatty Acids, Unsaturated / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D028361:Mitochondrial Diseases / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
D005231:Fatty Acids, Unsaturated; D010743:Phospholipids; D014280:Triglycerides; D044942:Acyl-CoA Dehydrogenase, Long-Chain