Correlation between medium C-chain fatty acids and polyunsaturated fatty acids

The medium C-chain fatty acids increased in the muscle, lungs, pancreas and adipose tissue (and not in the liver) of the rats injected with CCl4 or nourished with "balanced" diet for the lipids. When CCl4 and balanced diet are furnished together, these acids decrease strongly: the discussion of the results is difficult.     

Partition of fatty acids

The partition ratios of radioactive fatty acids between n-heptane and a physiological buffer at 37 degrees C were measured. The fatty acids included the saturated acids with an even number of carbons from 10 to 18 and the unsaturated acids oleic, linoleic, and linolenic. In addition, the partition ratios of decanoate, myristate, and palmitate were determined over a wide pH range. Any single plot of partition ratio vs. aqueous concentration of an acid gave a nearly straight line, a finding consistent with very little association in the aqueous phase. In the case of the acids with 16 and 18 carbon atoms, however, comparison of the constants calculated from these plots with the assumption of no aqueous phase association revealed several inconsistencies. These inconsistencies cannot be resolved completely by assuming the existence of fatty acid association in the aqueous solution. We believe that at least some of the deviations are due to the presence of trace quantities of radioactive impurities in the labeled fatty acids. For example, purification of a sample of supposedly pure [1-(14)C]myristate by a series of solvent extractions increased the partition ratio by a factor of 1.5. Although all of the observations cannot be explained by this interpretation, we believe that our studies suggest that there is no appreciable association of fatty acids under the usual physiological conditions.     

Synthesis of unsaturated fatty acids

This article reviews synthetic routes leading to polyunsaturated fatty acids having “skipped” double bonds. Emphasis is placed on the “acetylenic approach”.The suitability of building blocks, their condensation reactions as well as the controlled reduction of triple bonds to cis double bonds are discussed. In addition, the application of the various methods to the preparation of polyunsaturated fatty acids labelled with ³H and/or ¹⁴C at distinct positions of the molecules is reviewed.     

Intestinal metabolism of fatty acids

1. The effect of concentration on the oxidation and incorporation into lipids of lauric acid and linoleic acid by rings of rat small intestine has been studied in vitro. 2. In the absence of glucose, the oxidation of lauric acid in the range 0.01-5.0mm showed a maximum at 0.1mm. In the presence of glucose the maximum was at 0.5mm. The oxidation of linoleic acid in the presence of glucose increased throughout the concentration range 0.01-5.0mm. 3. The incorporation of lauric acid into lipids was maximal at 0.5-0.6mm in the presence of glucose, but at 10mm in the absence of glucose. At 0.8mm-lauric acid, in the presence of glucose, over 75% of the incorporated lauric acid was in triglycerides, but at 10mm they only contained 30%. The incorporation of glucose carbon into glycerides paralleled the incorporation of lauric acid. 4. In the range 0.01-2.5mm-linoleic acid the quantity incorporated into lipids increased. In the range 0.01-0.4mm linoleic acid was incorporated predominantly into triglycerides, but between 0.4 and 1.0mm most was in diglycerides, and between 2.5 and 5.0mm most was in monoglycerides. 5. The relationship of fatty acid concentration to the mechanism of absorption is discussed, together with the correlation between the distribution of the absorbed fatty acids within the tissue lipids and the lipase activity of intestinal mucosa.     

Long chain fatty acids inhibit and medium chain fatty acids activate mammalian cardiac hexokinase

We investigated the effect of non-esterified fatty acids (FAs) on bovine heart hexokinase (type I: ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1). Long chain FAs (C14 to C20) inhibited the enzyme in a way that correlated positively with both the chain length and the degree of unsaturation. Medium chain FA with 12 or less carbons activated hexokinase in a chain length dependent manner with the greater activation shown by laurate. The activation constant of laurate was 91.5 microM with a maximal activation of 60.3%. Oleate caused a maximal decrease in specific activity of 25% with an inhibition constant of 79 microM. Using the fluorescent probe cis-parinarate, we found a saturable binding site with K(d) of 3.5 microM. Oleate competed the fluorescent probe from the protein with a K(d) of 1.4 microM. Medium chain FAs did not compete the probe from HK. The binding of fatty acid to the protein appears to be entropically driven as indicated by an Arrhenius analysis (DeltaS=+231.6 J mol(-1) deg(-1)). The presence of oleate significantly increased the K(ATP)(m) from 0.47 mM to 0.89 mM while the K(glucose)(m) in the presence of the FA (0.026+/-0.003 mM) was not significantly different from the control (0.014+/-0.004 mM). A decrease in V(max) values in the presence of oleate indicated that a mixed allosteric inhibition was operating.