Quantitative measurement of total and free 3-hydroxy fatty acids in serum or plasma samples: short-chain 3-hydroxy fatty acids are not esterified.
Diagnostic protocols for disorders of mitochondrial fatty acid oxidation (FAO) generally include the measurement of plasma acylcarnitines. Many biochemical intermediates of FAO resulting from a metabolic block require carnitine conjugation for transport out of the mitochondria, and so occur as fatty acid carnitine conjugates in the blood. Both short- and long-chain acylcarnitines are generally determined, and this procedure has a critical role to play in the diagnosis of disorders of the very long-chain, medium-chain and short-chain acyl-CoA dehydrogenase defects. Less is known about the utility of acylcarnitines for the measurement of the various chain length intermediates of the 3-hydroxyacyl-CoA dehydrogenase steps of beta-oxidation. This study utilizes stable-isotope dilution gas chromatography-mass spectrometry to determine the serum or plasma concentrations of free 3-hydroxy fatty acids (3-OHFAs) of chain lengths C6 to C16. The 3-OHFA concentrations are determined in samples from normal individuals, hyperketotic individuals and patients with long-chain L-3-hydroxyacyl-CoA dehydrogenase and short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiencies, both before and after hydrolysis. The results of the study indicate the relative amounts of conjugated intermediates of all chain lengths. Long-chain 3-OHFAs (C14 and C16) are found in elevated concentrations after hydrolysis, whereas short-chain and medium-chain 3-OHFAs (C6 to C12) show no difference in concentrations between the two samples in all subjects tested, suggesting that only long-chain 3-hydroxy species form conjugates. This finding has important implications for the use of the acylcarnitine assay for the diagnosis of defects involving short-chain and medium-chain 3-hydroxy fatty acids.
Jones
P M
PM
Department of Pathology, University of Texas, Southwestern Medical Center, Dallas, USA. pjones@childmed.dallas.tx.us
Burlina
A B
AB
Bennett
M J
MJ
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000097:blood / Q000172:deficiency*; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000097:blood / Q000172:deficiency*; D004951:Esterification; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D006801:Humans; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase
D005230:Fatty Acids, Nonesterified; D015094:3-Hydroxyacyl CoA Dehydrogenases; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain