l-Carnitine is essential to β-oxidation of quarried fatty acid from mitochondrial membrane by PLA2

Yano, Hiromi; Oyanagi, Eri; Kato, Yasuko; Samejima, Yoshiyuki; Sasaki, Junzo; Utsumi, Kozo

doi:10.1007/s11010-010-0472-z

Cited by 26 publications

(25 citation statements)

References 27 publications

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“…It is an essential cofactor in the transfer of fatty acyl groups into the mitochondrial matrix, where they undergo beta-oxidation [6,12]. Carnitine also plays a role in the transfer of acetyl and other short acyl groups from peroxisomes to mitochondria for further oxidation [13].…”

Section: Discussionmentioning

confidence: 99%

“…A large body of evidence suggests that carnitine and its derivatives acetyl-L-carnitine and propionyl-L-carnitine enhance glucose utilization by stimulating the activity of pyruvate dehydrogenase complex [9], which is a key enzymatic complex in glucose oxidation, because intramitochondrial acetyl-CoA can be converted with carnitine into acetyl-L-carnitine (ALC) via the carnitine acetyltransferase that is then transported out of the mitochondria [10]. L-Carnitine is an amine key substrate in a family of carnitine acyltransferases, transferred reversibly between active units of acyl carnitine and co-enzyme A to preserve homoeostasis for a wide range of traffic that are crucial for acyl intermediary metabolism and cellular regulation [11].Various analogues of L-carnitine have been synthesized to study their mode of action and the structural features of their binding sites [12,13]. The phosphorus analogues of naturally occurring amino acids, which are produced by certain organisms, are of great interest in bioorganic and medicinal chemistry.…”

mentioning

confidence: 99%

“…Various analogues of L-carnitine have been synthesized to study their mode of action and the structural features of their binding sites [12,13]. The phosphorus analogues of naturally occurring amino acids, which are produced by certain organisms, are of great interest in bioorganic and medicinal chemistry.…”

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Pharmacological Evaluation of a β‐Hydroxyphosphonate Analogue of l‐Carnitine in Obese Zucker fa/fa Rats

Reyes‐Esparza

Mendoza-Rivera

Cruz-Cordero³

et al. 2012

Basic Clin Pharma Tox

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In this study, we evaluated the effect of an analogue of L-carnitine on parameters involved with Metabolic Syndrome in obese Zucker rats. Twenty-four rats were treated for 5 weeks with L-carnitine (300 mg/kg) and its analogue at two concentrations (100 and 250 mg/kg) to assess their impact on glucose, triglycerides and cholesterol in liver and blood samples, as well as the amount of liver glycogen. Liver slices were also analysed. The analogue reduced the levels of glucose, triglycerides and cholesterol in liver and the level of triglycerides in serum. At 100 mg/kg, the analogue proved more effective than L-carnitine in improving the biochemical alterations present in liver. The amount of liver glycogen content was higher in obese animals treated with both L-carnitine and the analogue. No changes on insulin and leptin were observed in animals treated. L-carnitine and its analogue reduced the microvesicular fatty infiltration in liver. This study demonstrated that the analogue tested is more potent and efficient than L-carnitine and improves the pharmacological profile of L-carnitine.Metabolic syndrome, syndrome 'X' or insulin resistance syndrome has been the focus of attention during the past 80 years [1]. Its importance lies in its multiple, interrelated risk factors for metabolic origin, which can lead to the development of diseases such as atherosclerosis, type 2 diabetes mellitus, dyslipidaemia, high blood pressure, elevated plasma glucose, prothrombotic state and pro-inflammatory state [2]. Other factors associated with metabolic syndrome are abdominal obesity, insulin resistance and cardiovascular diseases (CVD) [3]. The main causes for the increase in the disease are obesity and diabetes mellitus among populations with a sedentary life pattern [4,5].L-carnitine is synthesized by mammals as a result of the synthesis of amino acids such as lysine or methionine and is also obtained from the diet [6,7]. Carnitine is an essential factor in transporting the long-chain fatty acids (acyl CoA) from the cytoplasm into the mitochondria where the beta-oxidation takes place [8]. A large body of evidence suggests that carnitine and its derivatives acetyl-L-carnitine and propionyl-L-carnitine enhance glucose utilization by stimulating the activity of pyruvate dehydrogenase complex [9], which is a key enzymatic complex in glucose oxidation, because intramitochondrial acetyl-CoA can be converted with carnitine into acetyl-L-carnitine (ALC) via the carnitine acetyltransferase that is then transported out of the mitochondria [10]. L-Carnitine is an amine key substrate in a family of carnitine acyltransferases, transferred reversibly between active units of acyl carnitine and co-enzyme A to preserve homoeostasis for a wide range of traffic that are crucial for acyl intermediary metabolism and cellular regulation [11].Various analogues of L-carnitine have been synthesized to study their mode of action and the structural features of their binding sites [12,13]. The phosphorus analogues of naturally occurring amino ac...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Pharmacological Evaluation of a β‐Hydroxyphosphonate Analogue of l‐Carnitine in Obese Zucker fa/fa Rats

Reyes‐Esparza

Mendoza-Rivera

Cruz-Cordero³

et al. 2012

Basic Clin Pharma Tox

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“…L-carnitine increases the rate of fatty acid transport to the mitochondria and, in fact, has been shown to be essential to b-oxidation of quarried fatty acids from the mitochondrial membrane. (26,27) It has been shown that administration of exendin-4 leads to the reduction of oxidative stress in steatotic models. (23) It protects the hepatocytes from ischemic injury by inhibiting cell death and stimulation of lipolysis.…”

Section: Reduction Of Iri and Steatosis With Nelpmentioning

confidence: 99%

Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers

Banan¹,

Watson²,

Xu³

et al. 2016

Liver Transpl

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Donor organ shortages have led to an increased interest in finding new approaches to recover organs from extended criteria donors (ECD). Normothermic extracorporeal liver perfusion (NELP) has been proposed as a superior preservation method to reduce ischemia/reperfusion injury (IRI), precondition suboptimal grafts, and treat ECD livers so that they can be successfully used for transplantation. The aim of this study was to investigate the beneficial effects of a modified NELP circuit on discarded human livers. Seven human livers that were rejected for transplantation were placed on a modified NELP circuit for 8 hours. Perfusate samples and needle core biopsies were obtained at hourly intervals. A defatting solution that contained exendin-4 (50 nM) and L-carnitine (10 mM) was added to the perfusate for 2 steatotic livers. NELP provided normal temperature, electrolytes, and pH and glucose levels in the perfusate along with physiological vascular flows and pressures. Functional, biochemical, and microscopic evaluation revealed no additional injuries to the grafts during NELP with an improved oxygen extraction ratio (>0.5) and stabilized markers of hepatic injury. All livers synthesized adequate amounts of bile and coagulation factors. We also demonstrated a mild reduction (10%) of macroglobular steatosis with the use of the defatting solution. Histology demonstrated normal parenchymal architecture and a minimal to complete lack of IRI at the end of NELP. In conclusion, a modified NELP circuit preserved hepatocyte architecture, recovered synthetic functions, and hepatobiliary parameters of ECD livers without additional injuries to the grafts. This approach has the potential to increase the donor pool for clinical transplantation. The major limiting factor of using extended criteria donor (ECD) grafts is their greater susceptibility to injury during cold preservation and lower tolerance for ischemia/reperfusion injury (IRI) upon reperfusion. Therefore, ECD grafts have been associated with a higher risk of posttransplant complications such as primary graft nonfunction and chronic cholangiopathy.(1-4) Machine perfusion has been investigated both as a preservation method to reduce IRI in ECD livers and as a method to assess the viability and function of suboptimal grafts prior to transplantation.(5-7)Currently, there are 3 variants of liver machine perfusion that are distinguished by the perfusate temperature: hypothermic, subnormothermic, and normothermic.

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“…Carnitine is essential for the β-oxidation of fatty acids in mitochondria to generate adenosine triphosphate (ATP) in living cells (12,13). Under normal conditions, 70-80% of human carnitine is obtained through dietary means, although the liver, kidney and brain are capable of biosynthesizing carnitine from lysine and methionine.…”

Section: Introductionmentioning

confidence: 99%

Carnitine-induced senescence in glioblastoma cells

Yamada

Matsuda

Nishimura

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. Carnitine is essential for lipid metabolism in cells and is known to possess antioxidant properties. Previous reports have suggested that antioxidants are able to induce senescence in glioblastoma cells, consequently, in the present study, we investigated the effect of carnitine on glioblastoma cells. Under conditions of hyponutrition (undernutrition), the proliferation of glioblastoma cells was attenuated and the level of intracellular carnitine was increased. Glioblastoma cell proliferation was also attenuated in cultures that were supplemented with exogenous carnitine, where the induction of senescence was detected by senescence-associated β-gal (SA-β-gal) staining. However, there was no evidence of the induction of apoptosis. These effects were not detected when cells were cultured with carnitine plus an inhibitor of p38 mitogen-activated protein kinase (MAPK). It, therefore, appears that carnitine has antioxidant actions in normal cells but induces senescence, which may be regarded as an opposite phenomenon, in glioblastoma cells. Senescence has been reported in cells exposed to temozolomide, which is a standard drug used for the treatment of glioblastoma. Carnitine could, therefore, represent an attractive alternative therapy for glioblastoma.

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l-Carnitine is essential to β-oxidation of quarried fatty acid from mitochondrial membrane by PLA2

Cited by 26 publications

References 27 publications

Pharmacological Evaluation of a β‐Hydroxyphosphonate Analogue of l‐Carnitine in Obese Zucker fa/fa Rats

Pharmacological Evaluation of a β‐Hydroxyphosphonate Analogue of l‐Carnitine in Obese Zucker fa/fa Rats

Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers

Carnitine-induced senescence in glioblastoma cells

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