Relative activity of unsaturated fatty acid metabolic pathways in humans

The four families of unsaturated fatty acids (w9, w7, w6, w3) appear to be elongated and desaturated by enzymes shared among all families. The order of relative pathway activity is hypothesized to be w3 greater than w6 greater than w9 greater than w7. In order to examine this question, we measured by high resolution capillary column gas-liquid chromatography, the relative concentrations of the various fatty acids in plasma from 20 healthy reference subjects, 33 randomly selected subjects from the Framingham Heart Study, and six patients with intestinal malabsorption and suspected severe essential fatty acid deficiency (SEFAD). The ratios of the concentrations of daughter (derivative) fatty acids (DFA) to parent (precursor) fatty acids (PFA) within each family was found to reflect the hypothesized pathway activity. DFA/PFA ratios were 10 to 20 times greater for w3 than for w6 fatty acids (P less than .01), and 5 to 10 times greater for w6 than w9 fatty acids (P less than .01). Patients with SEFAD had lower levels of w3 and w6 fatty acids than the other two groups (P less than .01), higher DFA/PFA in each family (P less than .01), and increased production of both PFA9 and DFA9, consistent with a previously shown shift towards production of w9 fatty acids and with regulation of the pathways by their end products. We also examined the rate of restoration of levels of DFA in the w3 and w6 families in a SEFAD patient intravenously fed soybean oil (55% linoleic acid and 8% linolenic acid). Levels of DFA3s were restored faster than levels of DFA6s, indicating higher w3 pathway activity.(ABSTRACT TRUNCATED AT 250 WORDS)