Rat liver outer mitochondrial carnitine palmitoyltransferase activity towards long‐chain polyunsaturated fatty acids and their CoA esters

Gavino, Grace; Gavino, Victor C.

doi:10.1007/bf02537135

Cited by 105 publications

(82 citation statements)

References 22 publications

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“…In one study of rat liver mitochondria, of the long-chain fatty acids tested, a-LNA had the highest rate of transfer by CPT-1, and DHA and 18:0 had the lowest rates (49). Showing that a-LNA taken up in heart was largely b-oxidized is consistent with these observations and with studies reporting a high b-oxidation rate of a-LNA in the whole animal (50).…”

Section: Discussionsupporting

confidence: 64%

Rat heart cannot synthesize docosahexaenoic acid from circulating α-linolenic acid because it lacks elongase-2

Igarashi

Chang

et al. 2008

Journal of Lipid Research

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The extent to which the heart can convert alinolenic acid (a-LNA, 18:3n-3) to longer chain n-3 PUFAs is not known. Conversion rates can be measured in vivo using radiolabeled a-LNA and a kinetic fatty acid model. [1-14 C]a-LNA was infused intravenously for 5 min in unanesthetized rats that had been fed an n-3 PUFA-adequate [4.6% a-LNA, no docosahexaenoic acid (DHA, 22:6n-3)] or n-3 PUFA-deficient diet (0.2% a-LNA, nor DHA) for 15 weeks after weaning. Arterial plasma was sampled, as was the heart after high-energy microwaving. Rates of conversion of a-LNA to longer chain n-3 PUFAs were low, and DHA was not synthesized at all in the heart. Most a-LNA within the heart had been b-oxidized. In deprived compared with adequate rats, DHA concentrations in plasma and heart were both reduced by .90%, whereas heart and plasma levels of docosapentaenoic acid (DPAn-6, 22:5n-6) were elevated. Dietary deprivation did not affect cardiac mRNA levels of elongase-5 or desaturases D6 and D5, but elongase-2 mRNA could not be detected. In summary, the rat heart does not synthesize DHA from a-LNA, owing to the absence of elongase-2, but must obtain its DHA entirely from plasma. Dietary n-3 PUFA deprivation markedly reduces heart DHA and increases heart DPAn-6, which may make the heart vulnerable to different insults.-Igarashi, M., K. Ma, L. Chang, J. M. Bell, and S. I. Rapoport. Rat heart cannot synthesize docosahexaenoic acid from circulating a-linolenic acid because it lacks elongase-2. J. Lipid Res. 2008Res. . 49: 1735Res. -1745 Supplementary key words diet • heart • deprivation • elongation • synthesis • n-3 polyunsaturated fatty acids Long-chain n-3 PUFAs, particularly eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA,, are reported to be protective against cardiovascular disease (1-8). Thus, a low dietary n-3 PUFA intake and a low plasma DHA concentration are risk factors for cardiac disease (8-10), whereas a high dietary n-3 PUFA content is considered protective (11-13).In some mammalian tissues, EPA and DHA can be converted from shorter chain a-linolenic acid (a-LNA, 18:3n-3), which is enriched in plant oils, by serial steps of desaturation, elongation, and b-oxidation (14-20). Using our kinetic method and model, we showed in unanesthetized rats that rates of conversion of a-LNA to DHA were higher in liver than in brain, and that n-3 dietary deprivation could further increase the liver but not brain rates, in relation to elevated expression of requisite desaturases and elongases (21-23). These enzymes include D5 and D6 desaturases and elongases-2 and -5. They are expressed in the liver and many other rodent tissues, although elongase-2 has not been identified in rat heart (15-17, 24, 25). Thus, the heart may be incapable of synthesizing DHA from a-LNA, consistent with one study on isolated rat cardiomyocytes (26).Because of the importance of n-3 PUFAs to cardiovascular function (see above), and because their kinetics have not been thoroughly examined in vivo, we thought it of interest in this study...

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Section: Discussionsupporting

confidence: 64%

Rat heart cannot synthesize docosahexaenoic acid from circulating α-linolenic acid because it lacks elongase-2

Igarashi

Chang

et al. 2008

Journal of Lipid Research

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“…Figure 7 shows that the CPTI activity towards 18:3n-3 was higher than towards 18:2n-6 and 18:1 n-9 and that the activity increased with the ratio of fatty acid/albumin and more rapidly for 18:3n-3. Gavino and Gavino (1991) have confirmed these results by measuring the CPT initial velocity and additionally showed that the initial velocity was very low for 20:4n-6 and 22:6n-3 but relatively high for 20:5n-3, studied as acyl-CoA. They suggested that acyl-CoA synthesis may also be important in the control of the entry of fatty acids into the mitochondria, in addition to specificity of CPTI to fatty acyl-CoA.…”

Section: Dietary Sources Of Essential Fatty Acidssupporting

confidence: 56%

The metabolism and availability of essential fatty acids in animal and human tissues

Bézard

Blond²,

Bernard³

et al. 1994

Reprod. Nutr. Dev.

191

109

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Summary ― Essential fatty acids (EFA), which are not synthesized in animal and human tissues, belong to the n-6 and n-3 families of polyunsaturated fatty acids (PUFA), derived from linoleic acid (LA,) and a-linolenic acid (LNA,. Optimal requirements are 3-6% of ingested energy for LA and 0.5-1% for LNA in adults. Requirements in LNA are higher in development. Dietary sources of LA and LNA are principally plants, while arachidonic acid (AA,) is found in products from terrestrian animals, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)

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“…A similar selectivity may account for why esterifi ed DHA derived from circulating ␣ -LNA is synthesized and secreted at a higher rate than is esterifi ed EPA (see below) ( 29 ). Selectivity may be related to comparative rates of ␤ -oxidation within the liver of newly formed EPA, DPA, and DHA ( 43,44 ). The brain incorporates unesterifi ed DHA from plasma at a rate of 0.23 mol/day in rats on the same diet ( 45 ).…”

Section: Concentrations Of Esterifi Edmentioning

confidence: 97%

Whole-body synthesis secretion of docosahexaenoic acid from circulating eicosapentaenoic acid in unanesthetized rats

Gao

Kiesewetter

Chang

et al. 2009

Journal of Lipid Research

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( 5-7 ), bipolar disorder ( 8 ), and other human brain disorders. DHA also is considered important for optimum cardiac function ( 9 ), but it cannot be synthesized from its n-3 PUFA precursors in the heart due to a lack of elongase-2 ( 10 ).Some but not all clinical studies have indicated that dietary fi sh and marine oils that contain DHA and eicosapentaenoic acid (EPA), as well as dietary DHA or EPA given alone, can reduce brain or heart disease ( 7,(11)(12)(13)(14)(15)(16). Some of the EPA effects on these organs could be direct, as dietary EPA can lower plasma triacylglycerol ( 17,18 ), is a more potent platelet inhibitor than DHA ( 19,20 ), and its products have strong anti-infl ammatory effects ( 21 ). Other EPA effects may be indirect, through its conversion to DHA in the liver ( 22 ). Studies using compartmental analysis in humans ( 23 ) and in rats ( 24 ) fed ␣ -linolenic acid ( ␣ -LNA; 18:3n-3) or EPA labeled with a stable isotope reported that both ␣ -LNA and EPA were converted to DHA.To date, the rate of liver conversion of EPA to secreted DHA has not been quantifi ed directly in the intact organism. Knowing this rate in humans might help to estimate daily dietary requirements of . To measure this rate in rats for the fi rst time, in this article we employed a published method that was used to determine whole-body DHA synthesis secretion from circulating ␣ -LNA ( 29 ) in unanesthetized adult rats on an n-3 PUFAcontaining diet. [U-13 C]EPA was infused intravenously for 2 h, which allowed the establishment of a steady-state DHA synthesis secretion after about 1 h. Operational equations were used to calculate whole-body synthesis secretion rates of esterifi ed docosapentaenoic acid (DPA) and DHA and Abstract Dietary docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) are considered important for maintaining normal heart and brain function, but little EPA is found in brain, and EPA cannot be elongated to DHA in rat heart due to the absence of elongase-2. Ingested EPA may have to be converted in the liver to DHA for it to be fully effective in brain and heart, but the rate of conversion is not agreed on. This rate was determined in male adult rats fed a standard n-3 PUFA, containing diet by infusing unesterifi ed albumin-bound [U- C]EPA intravenously for 2 h and measuring esterifi ed [13 C]labeled PUFAs in arterial plasma lipoproteins, as well as the specifi c activity of unesterifi ed plasma EPA. Whole-body (presumably hepatic) synthesis secretion rates from circulating unesterifi ed EPA, calculated from peak fi rst derivatives of plasma esterifi ed concentration × volume curves, equaled 2.61 mol/day for docosapentaenoic acid (22:5n-3) and 5.46 mol/day for DHA. The DHA synthesis rate was 24-fold greater than the reported brain DHA consumption rate in rats. Thus, dietary EPA could help to maintain brain and heart DHA homeostasis because it is converted at a relatively high rate in the liver to circulating DHA. -Gao, F., D. Kiesewetter, L. Chang, K. Ma, S. I. Rapoport, and M. Igara...

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Rat liver outer mitochondrial carnitine palmitoyltransferase activity towards long‐chain polyunsaturated fatty acids and their CoA esters

Cited by 105 publications

References 22 publications

Rat heart cannot synthesize docosahexaenoic acid from circulating α-linolenic acid because it lacks elongase-2

Rat heart cannot synthesize docosahexaenoic acid from circulating α-linolenic acid because it lacks elongase-2

The metabolism and availability of essential fatty acids in animal and human tissues

Whole-body synthesis secretion of docosahexaenoic acid from circulating eicosapentaenoic acid in unanesthetized rats

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