Pathway of α-linolenic acid through the mitochondrial outer membrane in the rat liver and influence on the rate of oxidation. Comparison with linoleic and oleic acids

Abstract

The movement of alpha-linolenic acid (C18:3, n-3) through the mitochondrial outer membrane to oxidation sites was studied in rat liver and compared with the movement of linoleic acid (C18:2, n-6) and oleic acid (C18:1, n-9). All differ in the degree of unsaturation, but have the same chain length and the same position of the first double bond when counted from the carboxyl end. The following results were obtained. (1) The overall beta-oxidation in total mitochondria was in the order C18:3, n-3 greater than C18:2, n-6 greater than C18:1, n-9, independent of the amount of albumin in the medium. (2) The rate of formation of acylcarnitine from acyl-CoA was higher with oleoyl-CoA than with linoleoyl-CoA, and remained very low with alpha-linolenoyl-CoA for all concentrations studied. (3) When the formation of acylcarnitines originated from fatty acids (as potassium salts) in a medium containing CoA and ATP, the conversion of alpha-linolenate was greater than that of linoleate, which in turn was greater than that of oleate. (4) Use of a more purified mitochondrial fraction, practically devoid of peroxisomes, did not modify the results obtained with alpha-linolenate. (5) alpha-Linolenoyl-CoA did not inhibit oxidation of labelled alpha-linolenate, whereas the other acyl-CoAs did. (6) Transfer to carnitine of all three fatty acids (as potassium salts) by carnitine palmitoyltransferase-I (CPT-I) was similarly inhibited by increasing concentrations of malonyl-CoA. (7) On using a fraction containing mitochondrial outer membranes, the formation of acylcarnitines from potassium salts of fatty acids was qualitatively and quantitatively similar to that found with whole mitochondria. (8) Our observations show that alpha-linolenoyl-CoA synthesized other than in the mitochondria cannot be used to any great extent by the mitochondria due to its configuration. However when added as the unactivated form, alpha-linolenate appears to be very quickly oxidized, but should first be activated by acyl-CoA synthetase in the mitochondrion itself. Then it is rapidly channelled to CPT-I. These enzymic sites are probably close together in the mitochondrial outer membrane. The different behaviour of the alpha-linolenic group compared with the other acyl groups in the studied pathway can be explained by a different spatial arrangement due to the number and position of the double bonds.

Distinct metabolism of linoleic and linolenic acids in liver and adipose tissues of finishing Normande cull cows

“…Once in the hepatocytes, catabolism of FA is mostly directed towards synthesis of ketone bodies for energy utilisation by tissues (Reid and Husbands, 1985) as observed in our study in which products of LA and ALA oxidation were dominated by ASPs (.97% of total oxidation products). The higher rate of oxidation of ALA compared with that of LA is in agreement with previous data on rats (Clouet et al, 1989;Emmison et al, 1995) that showed that the rate of hepatic mitochondrial oxidation of 18:3n-3 was higher than that of 18:2n-6 mainly due to higher mitochondrial activity of carnitine palmitoyltransferase (Ide et al, 1996). As ALA is an essential FA, the extent of its partitioning towards b-oxidation is somewhat counterintuitive.…”

Conversion of α-linolenic acid to longer-chain polyunsaturated fatty acids in human adults

“…This may reflect lower muscle mass in women, and the potential overall effect would be to increase availability of αLNA for conversion to longer chain PUFA in women compared to men. The extent of partitioning of αLNA towards β-oxidation, when assessed under identical conditions, was almost twice that of palmitic, stearic and oleic acids [29], which may reflect the higher affinity of carnitine palmitoyl trasnsferase-1 for αLNA [32]. Since αLNA is essential in the human diet, this finding is somewhat counterintuitive and there is currently no explanation for the preferential use of αLNA as an energy source.…”

“…While there are advantages in terms of safety, there are unresolved issues regarding standardisation of quantification of data (particularly how conversion between fatty acids should be estimated), kinetic modelling, variation between subjects including age and gender, the method of administration of the labelled fatty acid, the duration of the study, the extent to which the background diet is controlled and the use of measurements of labelled fatty acids in blood (including which lipid pool should be measured) as a marker of fatty acid metabolism within tissues [53]. Together these factors have resulted in considerable heterogeneity in the findings of studies of αLNA metabolism in humans using stable isotope tracers [21,23,25,27,32,[54][55][56][57]. This presents a considerable challenge to any attempt to reach a consensus view on αLNA metabolism in man.…”

Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults

“…17,18 Although fat intake 19,20 and genotype 21,22 interact to regulate fat deposition, there are both in vitro 1,23 and in vivo 24,25 data which suggest that dietary fatty acid composition modulates to some extent the partitioning of fat between oxidation and storage.…”