Palmitoylcarnitine, a surface‐active metabolite

Goñi, Félix M.; Requero, M. Asun; Alonso, Alicia

doi:10.1016/0014-5793(96)00603-5

Cited by 56 publications

(33 citation statements)

References 43 publications

(49 reference statements)

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“…Furthermore, treatment of pregnant rats with carnitine resulted in a significant increase in total phospholipids and dipalmitoylphosphatidylcholine levels in fetal rat lungs (19,21). Palmitoylcarnitine is a form of carnitine that has been reported to have properties as a surface active molecule or surfactant, and functions as an intermediate in mitochondrial fatty acid oxidation (22). Palmitoylcarnitine may decrease the surface tension of the alveoli, and deficiency in palmitoylcarnitine may lead to the development of RDS.…”

Section: Discussionmentioning

confidence: 99%

Effects of L-carnitine supplementation on respiratory distress syndrome development and prognosis in premature infants: A single blind randomized controlled trial

Öztürk

Kardaş²,

Kardaş

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the efficacy of L-carnitine therapy on the occurrence and prognosis of respiratory distress syndrome (RDS). A single blind, randomized controlled trial study was conducted on 130 infants with gestational ages of 28-36 weeks. Infants were assigned to experimental groups (groups 1 and 2) and control groups (groups 3 and 4). Groups 1 and 3 consisted of infants with RDS, and groups 2 and 4 groups were composed of infants without RDS. The experimental groups were treated with carnitine. No statistically significant differences in serum carnitine levels were detected between the study and the control groups on day 1 of treatment (P=0.06). However, on day 7 of treatment, serum carnitine levels in the experimental groups were significantly increased (P= 0.02), as compared with the control groups. The surfactant requirement value, which is how many rounds of surfactant therapy were required, was 1.56±0.97 in group 1, and 2.12±0.99 in group 3 (P<0.001). The mean duration of mechanical ventilation required was 3.04±3.60 days in group 1, and 4.73±5.63 days in group 3 (P<0.001). The present results indicate that carnitine supplementation in premature infants with RDS may help to increase carnitine levels, thus decreasing the duration of mechanical ventilation and surfactant requirement.

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Section: Discussionmentioning

confidence: 99%

Effects of L-carnitine supplementation on respiratory distress syndrome development and prognosis in premature infants: A single blind randomized controlled trial

Öztürk

Kardaş²,

Kardaş

et al. 2015

Experimental and Therapeutic Medicine

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“…The large amounts of acyl-CoA and acylcarnitine that accumulate in the mitochondrial matrix during ischemia accelerate mPTP opening and are directly released into the cytosol along with cytochrome c after mPTP opening (9,39,40). Prolonged Ca 2ϩ -induced opening of the mPTP that is facilitated by Ca 2ϩ activation of iPLA 2 ␥ causes irreversible dissipation of the mitochondrial membrane potential and loss of membrane integrity leading to extensive mitochondrial damage (41).…”

Section: Discussionmentioning

confidence: 99%

Cardiac Myocyte-specific Knock-out of Calcium-independent Phospholipase A2γ (iPLA2γ) Decreases Oxidized Fatty Acids during Ischemia/Reperfusion and Reduces Infarct Size

Moon

Mancuso

Sims

et al. 2016

Journal of Biological Chemistry

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Calcium-independent phospholipase A 2 ␥ (iPLA 2 ␥) is a mitochondrial enzyme that produces lipid second messengers that facilitate opening of the mitochondrial permeability transition pore (mPTP) and contribute to the production of oxidized fatty acids in myocardium. To specifically identify the roles of iPLA 2 ␥ in cardiac myocytes, we generated cardiac myocyte-specific iPLA 2 ␥ knock-out (CMiPLA 2 ␥KO) mice by removing the exon encoding the active site serine (Ser-477). Hearts of CMiPLA 2 ␥KO mice exhibited normal hemodynamic function, glycerophospholipid molecular species composition, and normal rates of mitochondrial respiration and ATP production. In contrast, CMiPLA 2 ␥KO mice demonstrated attenuated Ca 2؉ -induced mPTP opening that could be rapidly restored by the addition of palmitate and substantially reduced production of oxidized polyunsaturated fatty acids (PUFAs). Furthermore, myocardial ischemia/reperfusion (I/R) in CMiPLA 2 ␥KO mice (30 min of ischemia followed by 30 min of reperfusion in vivo) dramatically decreased oxidized fatty acid production in the ischemic border zones. Moreover, CMiPLA 2 ␥KO mice subjected to 30 min of ischemia followed by 24 h of reperfusion in vivo developed substantially less cardiac necrosis in the area-atrisk in comparison with their WT littermates. Furthermore, we found that membrane depolarization in murine heart mitochondria was sensitized to Ca 2؉ by the presence of oxidized PUFAs. Because mitochondrial membrane depolarization and calcium are known to activate iPLA 2 ␥, these results are consistent with salvage of myocardium after I/R by iPLA 2 ␥ loss of function through decreasing mPTP opening, diminishing production of proinflammatory oxidized fatty acids, and attenuating the deleterious effects of abrupt increases in calcium ion on membrane potential during reperfusion.The salvage of jeopardized regions of myocardium during ischemia/reperfusion (I/R) 3 has been a long-standing goal of heart research. Because mortality and morbidity are related to infarct size, a variety of hemodynamic, metabolic, and pharmacological approaches have been used to reduce the severity of myocardial infarction during ischemia (1-3). Recent studies have accumulated evidence that the irreversible opening of the mitochondrial permeability transition pore (mPTP) upon oxidative stress is a principal mechanism of apoptotic/necrotic cardiac cell death accounting for the majority of I/R injury (4 -6). Although therapies for acute ischemia (e.g. reperfusion) have been extensively studied, at present there is no therapy for attenuating mPTP opening during reperfusion of ischemic zones in myocardium.Although the precise chemical composition of the mPTP is incompletely understood (6), a variety of initiators and modulators of mPTP opening has been identified (7,8). For example, during reperfusion, the reoxygenation of ischemic tissue results in mitochondrial Ca 2ϩ overload and renormalization of intracellular and matrix pH, which are accompanied by the prodigious generation of reactive oxygen s...

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“…Long-chain acyl-CoA esters were, in comparison with fatty acids and lysophospholipids, the most potent disrupter of membrane bilayers [4]. In contrast, it has been shown that only acylcarnitines, and not acyl-CoAs, are able to disrupt membrane barriers to solutes and produce complete membrane solubilization [6,7,9,10].…”

Section: Physical Properties Of Long-chain Acyl-coa Esters and Their mentioning

confidence: 99%

Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling

Færgeman¹,

Knudsen²

1997

Biochemical Journal

624

477

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The intracellular concentration of free unbound acyl-CoA esters is tightly controlled by feedback inhibition of the acyl-CoA synthetase and is buffered by specific acyl-CoA binding proteins. Excessive increases in the concentration are expected to be prevented by conversion into acylcarnitines or by hydrolysis by acyl-CoA hydrolases. Under normal physiological conditions the free cytosolic concentration of acyl-CoA esters will be in the low nanomolar range, and it is unlikely to exceed 200 nM under the most extreme conditions. The fact that acetyl-CoA carboxylase is active during fatty acid synthesis (Ki for acyl-CoA is 5 nM) indicates strongly that the free cytosolic acyl-CoA concentration is below 5 nM under these conditions. Only a limited number of the reported experiments on the effects of acyl-CoA on cellular functions and enzymes have been carried out at low physiological concentrations in the presence of the appropriate acyl-CoA-buffering binding proteins. Re-evaluation of many of the reported effects is therefore urgently required. However, the observations that the ryanodine-senstitive Ca2+-release channel is regulated by long-chain acyl-CoA esters in the presence of a molar excess of acyl-CoA binding protein and that acetyl-CoA carboxylase, the AMP kinase kinase and the Escherichia coli transcription factor FadR are affected by low nanomolar concentrations of acyl-CoA indicate that long-chain acyl-CoA esters can act as regulatory molecules in vivo. This view is further supported by the observation that fatty acids do not repress expression of acetyl-CoA carboxylase or Δ9-desaturase in yeast deficient in acyl-CoA synthetase.

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Palmitoylcarnitine, a surface‐active metabolite

Cited by 56 publications

References 43 publications

Effects of L-carnitine supplementation on respiratory distress syndrome development and prognosis in premature infants: A single blind randomized controlled trial

Effects of L-carnitine supplementation on respiratory distress syndrome development and prognosis in premature infants: A single blind randomized controlled trial

Cardiac Myocyte-specific Knock-out of Calcium-independent Phospholipase A2γ (iPLA2γ) Decreases Oxidized Fatty Acids during Ischemia/Reperfusion and Reduces Infarct Size

Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling

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