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Acetyl carnitine AND propionyl carnitine

Judit Bene, Kinga Hadzsiev, Bela Melegh
Type 2 diabetes is a highly prevalent chronic metabolic disorder characterized by hyperglycemia and associated with several complications such as retinopathy, hyperlipidemia and polyneuropathy. The dysregulated fatty acid metabolism along with tissue lipid accumulation is generally assumed to be associated in the development of insulin resistance and T2D. Moreover, several studies suggest a central role for oxidative stress in the pathogenesis of the disease. Since L-carnitine (LC) has an indispensable role in lipid metabolism via its involvement in the β-oxidation of long-chain fatty acids and it has antioxidant properties as well, carnitine supplementation may prove to be an effective tool in the management of the clinical course of T2D...
March 7, 2018: Nutrition & Diabetes
Renata Collard, Tomas Majtan, Insun Park, Jan P Kraus
Propionic acidemia is caused by a deficiency of the enzyme propionyl coenzyme A carboxylase (PCC) located in the mitochondrial matrix. Cell-penetrating peptides, including transactivator of transcription (TAT), offer a potential to deliver a cargo into the mitochondrion. Here, we investigated the delivery of an α6 β6 PCC enzyme into mitochondria using the HIV TAT peptide at several levels: into isolated mitochondria, in patient fibroblast cells, and in a mouse model. Results from Western blots and enzyme activity assays confirmed the import of TAT-PCC into mitochondria, as well as into patient fibroblasts, where the colocalization of imported TAT-PCC and mitochondria was also confirmed by confocal fluorescence microscopy...
March 15, 2018: Molecular and Cellular Biology
Elin Strand, Eirik W Rebnord, Malin R Flygel, Vegard Lysne, Gard F T Svingen, Grethe S Tell, Kjetil H Løland, Rolf K Berge, Asbjørn Svardal, Ottar Nygård, Eva R Pedersen
Context: Carnitine and its metabolites are centrally involved in fatty acid metabolism. Although elevated circulating concentrations have been observed in obesity and insulin resistance, prospective studies examining whether these metabolites are associated with incident type 2 diabetes mellitus (T2D) are sparse. Objective: We performed a comprehensive evaluation of metabolites along the carnitine pathway relative to incident T2D. Design: A total of 2519 patients (73...
March 1, 2018: Journal of Clinical Endocrinology and Metabolism
Natasha E Schoeler, Gail Bell, Alan Yuen, Adam D Kapelner, Simon J R Heales, J Helen Cross, Sanjay Sisodiya
OBJECTIVE: In the absence of specific metabolic disorders, accurate predictors of response to ketogenic dietary therapies (KDTs) for treating epilepsy are largely unknown. We hypothesized that specific biochemical parameters would be associated with the effectiveness of KDT in humans with epilepsy. The parameters tested were β-hydroxybutyrate, acetoacetate, nonesterified fatty acids, free and acylcarnitine profile, glucose, and glucose-ketone index (GKI). METHODS: Biochemical results from routine blood tests conducted at baseline prior to initiation of KDT and at 3-month follow-up were obtained from 13 adults and 215 children with KDT response data from participating centers...
May 2017: Epilepsia
Ning Chen, Mi Yang, Muke Zhou, Jing Xiao, Jian Guo, Li He
BACKGROUND: Safe interventions to enhance cognitive function in cognitively healthy people would be very valuable for several reasons, including a better quality of life and professional success. While L-carnitine has been reported to enhance cognitive function in some conditions, its efficacy is disputed. The evidence of its efficacy for cognitively healthy people has not previously been systematically reviewed. OBJECTIVES: To assess the efficacy and safety of L-carnitine for the enhancement of cognitive function in people without cognitive impairment...
March 26, 2017: Cochrane Database of Systematic Reviews
María M Adeva-Andany, Laura López-Maside, Cristóbal Donapetry-García, Carlos Fernández-Fernández, Cristina Sixto-Leal
Branched-chain amino acids (leucine, isoleucine and valine) are structurally related to branched-chain fatty acids. Leucine is 2-amino-4-methyl-pentanoic acid, isoleucine is 2-amino-3-methyl-pentanoic acid, and valine is 2-amino-3-methyl-butanoic acid. Similar to fatty acid oxidation, leucine and isoleucine produce acetyl-coA. Additionally, leucine generates acetoacetate and isoleucine yields propionyl-coA. Valine oxidation produces propionyl-coA, which is converted into methylmalonyl-coA and succinyl-coA. Branched-chain aminotransferase catalyzes the first reaction in the catabolic pathway of branched-chain amino acids, a reversible transamination that converts branched-chain amino acids into branched-chain ketoacids...
June 2017: Amino Acids
Elin Strand, Eva R Pedersen, Gard F T Svingen, Thomas Olsen, Bodil Bjørndal, Therese Karlsson, Jutta Dierkes, Pål R Njølstad, Gunnar Mellgren, Grethe S Tell, Rolf K Berge, Asbjørn Svardal, Ottar Nygård
BACKGROUND: Excess levels of serum acylcarnitines, which are intermediate products in metabolism, have been observed in metabolic diseases such as type 2 diabetes mellitus. However, it is not known whether acylcarnitines may prospectively predict risk of cardiovascular death or acute myocardial infarction in patients with stable angina pectoris. METHODS AND RESULTS: This study included 4164 patients (median age, 62 years; 72% men). Baseline serum acetyl-, octanoyl-, palmitoyl-, propionyl-, and (iso)valerylcarnitine were measured using liquid chromatography/tandem mass spectrometry...
February 3, 2017: Journal of the American Heart Association
Qixiao Jiang, Chunbo Wang, Chan Xue, Lingfang Xue, Meiting Wang, Changhao Li, Ziwen Deng, Qian Wang
Perfluorooctanoic acid (PFOA), a persistent organic pollutant, is associated with developmental toxicity. This study investigated the mechanism of PFOA-induced developmental cardiotoxicity in chicken embryo, focusing on the interactions between developmental exposure to PFOA and the levels of l-carnitine (LC), acetyl-l-carnitine (ALC) and propionyl-l-carnitine (PLC) in the heart. To evaluate the developmental cardiotoxicity, fertile chicken eggs were exposed to 0.1, 0.5, 1, 2 or 5mg/kg PFOA via air cell injection...
December 2016: Environmental Toxicology and Pharmacology
Wendy Wambacq, Galena Rybachuk, Isabelle Jeusette, Kristel Rochus, Brigitte Wuyts, Veerle Fievez, Patrick Nguyen, Myriam Hesta
BACKGROUND: Research in cats has shown that increased fermentation-derived propionic acid and its metabolites can be used as alternative substrates for gluconeogenesis, thus sparing amino acids for other purposes. This amino acid sparing effect could be of particular interest in patients with kidney or liver disease, where this could reduce the kidneys'/liver's burden of N-waste removal. Since dogs are known to have a different metabolism than the obligatory carnivorous cat, the main objective of this study was to assess the possibility of altering amino acid metabolism through intestinal fermentation in healthy dogs...
June 28, 2016: BMC Veterinary Research
Mona Ascha, Zeneng Wang, Mustafa S Ascha, Raed Dweik, Nizar N Zein, David Grove, J Mark Brown, Stephanie Marshall, Rocio Lopez, Ibrahim A Hanouneh
AIM: To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis (AH). METHODS: We prospectively recruited patients with cirrhosis from AH (n = 23) and those with cirrhosis with acute decompensation (AD) from etiologies other than alcohol (n = 25). We used mass spectrometry to identify 29 metabolic compounds in plasma samples from fasted subjects. A receiver operating characteristics analysis was performed to assess the utility of biomarkers in distinguishing acute AH from alcoholic cirrhosis...
April 8, 2016: World Journal of Hepatology
Anna V Mathew, E Mitchell Seymour, Jaeman Byun, Subramaniam Pennathur, Scott L Hummel
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a distinct entity with unique pathophysiology. In the Dietary Approaches to Stop Hypertension in Diastolic Heart Failure (DASH-DHF) study, the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) was associated with improved blood pressure and cardiovascular function in 13 hypertensive patients with HFpEF. With the use of targeted metabolomics, we explored metabolite changes and their relationship with energy-dependent measures of cardiac function in DASH-DHF...
December 2015: Journal of Cardiac Failure
Mussie Ghezu Hadera, Tanya McDonald, Olav B Smeland, Tore W Meisingset, Haytham Eloqayli, Saied Jaradat, Karin Borges, Ursula Sonnewald
Epilepsy is a severe neurological disorder characterized by altered electrical activity in the brain. Important pathophysiological mechanisms include disturbed metabolism and homeostasis of major excitatory and inhibitory neurotransmitters, glutamate and GABA. Current drug treatments are largely aimed at decreasing neuronal excitability and thereby preventing the occurrence of seizures. However, many patients are refractory to treatment and side effects are frequent. Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy in adults...
February 2016: Neurochemical Research
April D Lake, Petr Novak, Petia Shipkova, Nelly Aranibar, Donald G Robertson, Michael D Reily, Lois D Lehman-McKeeman, Richard R Vaillancourt, Nathan J Cherrington
Nonalcoholic fatty liver disease (NAFLD) is a globally widespread disease of increasing clinical significance. The pathological progression of the disease from simple steatosis to nonalcoholic steatohepatitis (NASH) has been well defined, however, the contribution of altered branched chain amino acid metabolomic profiles to the progression of NAFLD is not known. The three BCAAs: leucine, isoleucine and valine are known to mediate activation of several important hepatic metabolic signaling pathways ranging from insulin signaling to glucose regulation...
March 2015: Amino Acids
Huan-ting Li, Zhen-huan Zhao, Hai-yan Ding, Le-xin Wang, Yu Cao
OBJECTIVE: to investigate the impact of craniotomy on oxidative stress and its effect on levels of plasma L-carnitine (LC). METHODS: plasma levels of reactive oxygen species, superoxide dismutase (SOD), glutathion peroxidase (GSH-Px), catalase (CAT), total antioxidative capacity (T-AOC), and thiobarbituric acid reactive substances (TBARS) were measured in 34 patients (26 males and 8 females, mean age 47.7 ± 6.7 years) before and after craniotomy. Plasma levels of LC, acetyl-L-carnitine (ALC), and propionyl-L-carnitine (PLC) were also measured before and after the craniotomy...
November 2014: Canadian Journal of Physiology and Pharmacology
Robert Ringseis, Janine Keller, Klaus Eder
PURPOSE: Loss of skeletal muscle mass, also known as muscle wasting or muscle atrophy, is a common symptom of several chronic diseases, such as cancer and infectious diseases. Due to the strong negative impact of muscle loss on patient's prognosis and quality of life, the development of efficacious treatment approaches to combat muscle wasting are of great importance. In order to evaluate the suitability of L-carnitine (LC) as an anti-wasting agent for clinical purposes the present review comprehensively summarizes the results from animal and clinical studies showing the effects of supplementation with LC or LC derivatives (acetyl-LC, propionyl-LC) on critical mechanisms involved in skeletal muscle loss under pathologic conditions, such as increased proteolysis, impaired protein synthesis, myonuclear apoptosis, inflammation, oxidative stress, and mitochondrial dysfunction...
August 2013: European Journal of Nutrition
Santica M Marcovina, Cesare Sirtori, Andrea Peracino, Mihai Gheorghiade, Peggy Borum, Giuseppe Remuzzi, Hossein Ardehali
Mitochondria play important roles in human physiological processes, and therefore, their dysfunction can lead to a constellation of metabolic and nonmetabolic abnormalities such as a defect in mitochondrial gene expression, imbalance in fuel and energy homeostasis, impairment in oxidative phosphorylation, enhancement of insulin resistance, and abnormalities in fatty acid metabolism. As a consequence, mitochondrial dysfunction contributes to the pathophysiology of insulin resistance, obesity, diabetes, vascular disease, and chronic heart failure...
February 2013: Translational Research: the Journal of Laboratory and Clinical Medicine
Anna Bogusiewicz, Thomas D Horvath, Shawna L Stratton, Donald M Mock, Gunnar Boysen
This work describes a novel liquid chromatography tandem MS (LC-MS/MS) method for the determination of ratios of acylcarnitines arising from acyl-CoA substrates and products that reflect metabolic disturbances caused by marginal biotin deficiency. The urinary ratios reflecting reduced activities of biotin-dependent enzymes include the following: 1) the ratio of 3-hydroxyisovalerylcarnitine : 3-methylglutarylcarnitine (3HIAc : MGc) for methylcrotonyl-CoA carboxylase; 2) the ratio of propionylcarnitine:methylmalonylcarnitine (Pc : MMc) for propionyl-CoA carboxylase (PCC); and 3) the ratio of acetylcarnitine : malonylcarnitine (Ac : Mc) for acetyl-CoA carboxylase...
September 2012: Journal of Nutrition
Mariano Malaguarnera
PURPOSE OF REVIEW: Carnitine and its derivatives are natural substances involved in both carbohydrate and lipid metabolism. This review summarizes the recent progress in the field in relation to the molecular mechanisms. RECENT FINDINGS: The pool of different carnitine derivatives is formed by acetyl-L-carnitine (ALC), propionyl-L-carnitine (PLC), and isovaleryl-carnitine. ALC may have a preferential effect on the brain tissue. ALC represents a compound of great interest for its wide clinical application in various neurological disorders: it may be of benefit in treating Alzheimer's dementia, depression in the elderly, HIV infection, chronic fatigue syndrome, peripheral neuropathies, ischemia and reperfusion of the brain, and cognitive impairment associated with various conditions...
March 2012: Current Opinion in Gastroenterology
Carmen Mingorance, Rosalía Rodríguez-Rodríguez, María Luisa Justo, María Alvarez de Sotomayor, María Dolores Herrera
Acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) are two naturally occurring carnitine derivates formed by carnitine acetyltransferase. The beneficial cardiovascular effects of ALC and PLC have been extensively evaluated in animals and humans during the last 20 years. For instance, many clinical trials have suggested ALC and PLC as potential strategies in the management of peripheral arterial disease, heart and cerebral ischemia, and congestive heart failure. As a result, several experts have already aimed to revise the clinical evidence supporting the therapeutic use of ALC and PLC...
2011: Vascular Health and Risk Management
Lena Burri, Bodil Bjørndal, Hege Wergedahl, Kjetil Berge, Pavol Bohov, Asbjørn Svardal, Rolf K Berge
The administration of tetradecylthioacetic acid (TTA), a hypolipidemic and anti-inflammatory modified bioactive fatty acid, has in several experiments based on high fat diets been shown to improve lipid transport and utilization. It was suggested that increased mitochondrial and peroxisomal fatty acid oxidation in the liver of Wistar rats results in reduced plasma triacylglycerol (TAG) levels. Here we assessed the potential of TTA to prevent tumor necrosis factor (TNF) α-induced lipid modifications in human TNFα (hTNFα) transgenic mice...
August 2011: Lipids
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