Physiology of L-carnitine in plants in light of the knowledge in animals and microorganisms.

L-carnitine is present in all living kingdoms where it acts in diverse physiological processes. It is involved in lipid metabolism in animals and yeasts, notably as an essential cofactor of fatty acid intracellular trafficking. Its physiological significance is poorly understood in plants, but L-carnitine may be linked to fatty acid metabolism among other roles. Indeed, carnitine transferases activities and acylcarnitines are measured in plant tissues. Current knowledge of fatty acid trafficking in plants rules out acylcarnitines as intermediates of the peroxisomal and mitochondrial fatty acid metabolism, unlike in animals and yeasts. Instead, acylcarnitines could be involved in plastidial exportation of de novo fatty acid, or importation of fatty acids into the ER, for synthesis of specific glycerolipids. L-carnitine also contributes to cellular maintenance though antioxidant and osmolyte properties in animals and microbes. Recent data indicate similar features in plants, together with modulation of signaling pathways. The biosynthesis of L-carnitine in the plant cell shares similar precursors as in the animal and yeast cells. The elucidation of the biosynthesis pathway of L-carnitine, and the identification of the enzymes involved, is today essential to progress further in the comprehension of its biological significance in plants.

Role of L-carnitine in female infertility.

BACKGROUND: L-carnitine (LC), and its acetylated form, acetyl L-carnitine (ALC), have immense functional capabilities to regulate the oxidative and metabolic status of the female reproductive system. The vulnerability of this system to free radicals demand for advanced strategies to combat them. For this purpose, the 'quasi vitamins' LC and ALC can be used either individually, or in combination with each other or with other antioxidants. MAIN BODY: This review (a) summarizes the effects of carnitines on female fertility along with the findings from various in vivo and in vitro studies involving human, animal and assisted reproductive technology, and (b) proposes their mechanism of actions in improving female fertility through their integrated actions on reducing cellular stress, maintaining hormonal balance and enhancing energy production. They reportedly aid ß-oxidation in oocytes, maintain its cell membrane stability by acetylation of phospholipids and amphiphilic actions, prevent free radical-induced DNA damage and also stabilize acetyl Co-A/Co-A ratio for adequate acetyl storage as energy supply to maintain the robustness of reproductive cells. CONCLUSION: While both LC and ALC have their applications in improving female fertility, ALC is preferred for its better antioxidant properties and LC for amelioration of energy supply to the cells. These beneficial effects show great promise in its application as a treatment option for women facing infertility disorders.

Does skeletal muscle carnitine availability influence fuel selection during exercise?

Fat and carbohydrate are the major fuel sources utilised for oxidative, mitochondrial ATP resynthesis during human skeletal muscle contraction. The relative contribution of these two substrates to ATP resynthesis and total energy expenditure during exercise can vary substantially, and is predominantly determined by fuel availability and exercise intensity and duration. For example, the increased ATP demand that occurs with an increase in exercise intensity is met by increases in both fat and carbohydrate oxidation up to an intensity of approximately 60-70 % of maximal oxygen consumption. When exercise intensity increases beyond this workload, skeletal muscle carbohydrate utilisation is accelerated, which results in a reduction and inhibition of the relative and absolute contribution of fat oxidation to total energy expenditure. However, the precise mechanisms regulating muscle fuel selection and underpinning the decline in fat oxidation remain unclear. This brief review will primarily address the theory that a carbohydrate flux-mediated reduction in the availability of muscle carnitine to the mitochondrial enzyme carnitine palmitoyltransferase 1, a rate-limiting step in mitochondrial fat translocation, is a key mechanism for the decline in fat oxidation during high-intensity exercise. This is discussed in relation to recent work in this area investigating fuel metabolism at various exercise intensities and taking advantage of the discovery that skeletal muscle carnitine content can be nutritionally increased in vivo in human subjects.

L-Carnitine and Acetyl-L-carnitine Roles and Neuroprotection in Developing Brain.

L-Carnitine functions to transport long chain fatty acyl-CoAs into the mitochondria for degradation by ß-oxidation. Treatment with L-carnitine can ameliorate metabolic imbalances in many inborn errors of metabolism. In recent years there has been considerable interest in the therapeutic potential of L-carnitine and its acetylated derivative acetyl-L-carnitine (ALCAR) for neuroprotection in a number of disorders including hypoxia-ischemia, traumatic brain injury, Alzheimer's disease and in conditions leading to central or peripheral nervous system injury. There is compelling evidence from preclinical studies that L-carnitine and ALCAR can improve energy status, decrease oxidative stress and prevent subsequent cell death in models of adult, neonatal and pediatric brain injury. ALCAR can provide an acetyl moiety that can be oxidized for energy, used as a precursor for acetylcholine, or incorporated into glutamate, glutamine and GABA, or into lipids for myelination and cell growth. Administration of ALCAR after brain injury in rat pups improved long-term functional outcomes, including memory. Additional studies are needed to better explore the potential of L-carnitine and ALCAR for protection of developing brain as there is an urgent need for therapies that can improve outcome after neonatal and pediatric brain injury.

L-carnitine contributes to enhancement of neurogenesis from mesenchymal stem cells through Wnt/ß-catenin and PKA pathway.

The identification of factors capable of enhancing neurogenesis has great potential for cellular therapies in neurodegenerative diseases. Multiple studies have shown the neuroprotective effects of L-carnitine (LC). This study determined whether neuronal differentiation of rat adipose tissue-derived mesenchymal stem cells (ADSCs) can be activated by LC. In this study, protein kinase A (PKA) and Wnt/ß-catenin pathways were detected to show if this activation was due to these pathways. The expression of LC-induced neurogenesis markers in ADSCs was characterized using real-time PCR. ELISA was conducted to assess the expression of cyclic adenosine monophosphate (cAMP) and PKA. The expression of ß-catenin, reduced dickkopf1 (DKK1), low-density lipoprotein receptor-related protein 5 (LRP5), Wnt1, and Wnt3a genes as Wnt/ß-catenin signaling members were used to detect the Wnt/ß-catenin pathway. It was observed that LC could promote neurogenesis in ADSCs as well as expression of some neurogenic markers. Moreover, LC causes to increase the cAMP levels and PKA activity. Treatment of ADSCs with H-89 (dihydrochloride hydrate) as PKA inhibitor significantly inhibited the promotion of neurogenic markers, indicating that the PKA signaling pathway could be involved in neurogenesis induction. Analyses of real-time PCR data showed that the mRNA expressions of ß-catenin, DKK1, LRP5c-myc, Wnt1, and Wnt3a were increased in the presence of LC. Therefore, the present study showed that LC promotes ADSCs neurogenesis and the LC-induced neurogenic markers could be due to both the PKA and Wnt/ß-catenin signaling pathway. Impact statement Neural tissue has long been believed as incapable of regeneration and the identification of cell types and factors capable of neuronal differentiation has generated intense interest. Mesenchymal stem cells (MSCs) are considered as potential targets for stem cell-based therapy. L-carnitin (LC) as an antioxidant may have neuroprotective effects in oxidative damage and possibly in neurodegenerative disorders. We have tried to evaluate the effect of LC as an antioxidant on the neurogenic differentiation of ADSCs in order to further elucidate the simultaneous effects on the capability of the neural regeneration. In this study, PKA and Wnt/ß-catenin signaling pathways were detected to see if LC could also activate these pathways. The results of this study showed that 200 µM LC promoted ADSCs neurogenic differentiation, and that it was correlated with the PKA and Wnt/ß-catenin signaling pathways.

L-Carnitine Protects Renal Tubular Cells Against Calcium Oxalate Monohydrate Crystals Adhesion Through Preventing Cells From Dedifferentiation.

BACKGROUND/AIMS: The interactions between calcium oxalate monohydrate (COM) crystals and renal tubular epithelial cells are important for renal stone formation but still unclear. This study aimed to investigate changes of epithelial cell phenotype after COM attachment and whether L-carnitine could protect cells against subsequent COM crystals adhesion. METHODS: Cultured MDCK cells were employed and E-cadherin and Vimentin were used as markers to estimate the differentiate state. AlexaFluor-488-tagged COM crystals were used in crystals adhesion experiment to distinguish from the previous COM attachment, and adhesive crystals were counted under fluorescence microscope, which were also dissolved and the calcium concentration was assessed by flame atomic absorption spectrophotometry. RESULTS: Dedifferentiated MDCK cells induced by transforming growth factor ß1 (TGF-ß1) shown higher affinity to COM crystals. After exposure to COM for 48 hours, cell dedifferentiation were observed and more subsequent COM crystals could bind onto, mediated by Akt/GSK-3ß/Snail signaling. L-carnitine attenuated this signaling, resulted in inhibition of cell dedifferentiation and reduction of subsequent COM crystals adhesion. CONCLUSIONS: COM attachment promotes subsequent COM crystals adhesion, by inducing cell dedifferentiation via Akt/GSK-3ß/Snail signaling. L-carnitine partially abolishes cell dedifferentiation and resists COM crystals adhesion. L-carnitine, may be used as a potential therapeutic strategy against recurrence of urolithiasis.

[Carnitine - mitochondria and beyond]. / Karnityna - mitochondria i nie tylko.

Carnitine [(3R)-3-hydroxy-4-(trimethylazaniumyl)butanoate] in mammals is mainly delivered with diet. It enters the cell due to the activity of organic cation/carnitine transporter OCTN2 (SLC22A5), it can be as well transported by CT2 (SLC22A16) and a transporter of neutral and basic amino acids ATB0, + (SLC6A14). The hydroxyl group of carnitine is able to form esters with organic acids (xenobiotics, fatty acids) due to the activity of acylcarnitine transferases. Carnitine is necessary for transfer of fatty acids to mitochondria: in functioning of the so-called carnitine shuttle an essential role is fulfilled by palmitoylcarnitine transferase 1, carnitine carrier (SLC25A20) in the inner mitochondrial membrane and palmitoylcarnitine transferase 2. Oxidation of fatty acids takes also place in peroxisomes. The produced medium-chain acyl derivatives are exported as acylcarnitines, most probably by OCTN3 (Slc22a21). It has been postulated that acylcarnitines can cross the outer mitochondrial membrane through the voltage-dependent anion channel (VDAC) and/or through the palmitoycarnitine transferase 1 oligomer. Mutations of genes coding carnitine plasma membrane transporters result in the primary carnitine deficiency, with symptoms affecting normal functioning of muscles (including heart) and brain. Mechanisms regulating functioning of these transporters have been presented with emphasis on their role as potential therapeutic targets.

Acylcarnitines--old actors auditioning for new roles in metabolic physiology.

Perturbations in metabolic pathways can cause substantial increases in plasma and tissue concentrations of long-chain acylcarnitines (LCACs). For example, the levels of LCACs and other acylcarnitines rise in the blood and muscle during exercise, as changes in tissue pools of acyl-coenzyme A reflect accelerated fuel flux that is incompletely coupled to mitochondrial energy demand and capacity of the tricarboxylic acid cycle. This natural ebb and flow of acylcarnitine generation and accumulation contrasts with that of inherited fatty acid oxidation disorders (FAODs), cardiac ischaemia or type 2 diabetes mellitus. These conditions are characterized by very high (FAODs, ischaemia) or modestly increased (type 2 diabetes mellitus) tissue and blood levels of LCACs. Although specific plasma concentrations of LCACs and chain-lengths are widely used as diagnostic markers of FAODs, research into the potential effects of excessive LCAC accumulation or the roles of acylcarnitines as physiological modulators of cell metabolism is lacking. Nevertheless, a growing body of evidence has highlighted possible effects of LCACs on disparate aspects of pathophysiology, such as cardiac ischaemia outcomes, insulin sensitivity and inflammation. This Review, therefore, aims to provide a theoretical framework for the potential consequences of tissue build-up of LCACs among individuals with metabolic disorders.

L-carnitine affects osteoblast differentiation in NIH3T3 fibroblasts by the IGF-1/PI3K/Akt signalling pathway.

Fibroblasts in soft tissues are one of the progenitors of ectopic calcification. Our previous experiment found that the serum concentrations of small metabolite L-carnitine (LC) decreased in an ectopic calcification animal model, indicating LC is a potential calcification or mineralization inhibitor. In this study, we investigated the effect of LC on NIH3T3 fibroblast osteoblast differentiation, and explored its possible molecular mechanisms. Two concentrations of LC (10 µM and 100 µM) were added in Pi-induced NIH3T3 fibroblasts, cell proliferation was compared by MTT assays, osteoblast differentiation was evaluated by ALP activity, mineralized nodules formation, calcium deposition, and expressions of the osteogenic marker genes. Our results indicated that 10 µM LC increased the proliferation of NIH3T3 cells, but 100 µM LC slightly inhibited cell proliferation. 100 µM LC inhibits NIH3T3 differentiation as evidenced by decreases in ALP activity, mineralized nodule formation, calcium deposition, and down-regulation of the osteogenic marker genes ALP, Runx2 and OCN, meanwhile 10 µM of LC exerts an opposite effect that promotes NIH3T3 osteogenesis. Mechanistically, 100 µM LC significantly inhibits IGF-1/PI3K/Akt signalling, while 10 µM LC slightly activates this pathway. Our study suggests that a decease in LC level might contribute to the development of ectopic calcification in fibroblasts by affecting IGF-1/PI3K/Akt, and addition of LC may benefit patients with ectopic calcification.

Lowered serum total L-carnitine levels are associated with obesity at term pregnancy.

OBJECTIVE: This study aims to compare the serum total l-carnitine concentrations of obese and non-obese pregnant women and to identify the role of L-carnitine in both maternal and fetal weight gain during pregnancy. METHOD: This study reviews 118 healthy women with singleton term pregnancy (≥37 weeks). The characteristics of the recruited subjects were analyzed according to their pre-pregnancy body mass index (BMI). RESULTS: The women with pre-pregnancy BMI < 18.5 kg/m(2) had significantly higher serum L-carnitine levels whereas the women with BMI > 29.9 kg/m(2) at term pregnancy had significantly lower serum l-carnitine levels (p = 0.001 for both). The neonates born to women with BMI > 29.9 kg/m(2) at term pregnancy had significantly longer height and wider head circumference (p = 0.001 for both). Serum total L-carnitine levels correlated significantly and negatively with pre-pregnancy body weight, pre-pregnancy BMI, pregnancy body weight, pregnancy BMI and serum triglyceride levels (r = -0.397, p = 0.001; r = -0.357, p = 0.001; r = -0.460, p = 0.001; r = -0.463, p = 0.001 and r = -0.216, p = 0.019, respectively). There was a significant and positive correlation between L-carnitine and HDL values (r = 0.243, p = 0.008). CONCLUSIONS: The crucial role of L-carnitine in pregnancy metabolism suggests that nutritional supplementation of this amino acid can be offered to women who are either overweight or obese at the beginning of the pregnancy.

Translating the basic knowledge of mitochondrial functions to metabolic therapy: role of L-carnitine.

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. The increased knowledge on mitochondria and their role in cellular metabolism is providing new evidence that these disorders may benefit from mitochondrial-targeted therapies. We review the current knowledge of the contribution of mitochondrial dysfunction to chronic diseases, the outcomes of experimental studies on mitochondrial-targeted therapies, and explore the potential of metabolic modulators in the treatment of selected chronic conditions. As an example of such modulators, we evaluate the efficacy of the administration of L-carnitine and its analogues acetyl and propionyl L-carnitine in several chronic diseases. L-carnitine is intrinsically involved in mitochondrial metabolism and function as it plays a key role in fatty acid oxidation and energy metabolism. In addition to the transportation of free fatty acids across the inner mitochondrial membrane, L-carnitine modulates their oxidation rate and is involved in the regulation of vital cellular functions such as apoptosis. Thus, L-carnitine and its derivatives show promise in the treatment of chronic conditions and diseases associated with mitochondrial dysfunction but further translational studies are needed to fully explore their potential.

Metabolomic analysis reveals that carnitines are key regulatory metabolites in phase transition of the locusts.

Phenotypic plasticity occurs prevalently and plays a vital role in adaptive evolution. However, the underlying molecular mechanisms responsible for the expression of alternate phenotypes remain unknown. Here, a density-dependent phase polyphenism of Locusta migratoria was used as the study model to identify key signaling molecules regulating the expression of phenotypic plasticity. Metabolomic analysis, using high-performance liquid chromatography and gas chromatography-mass spectrometry, showed that solitarious and gregarious locusts have distinct metabolic profiles in hemolymph. A total of 319 metabolites, many of which are involved in lipid metabolism, differed significantly in concentration between the phases. In addition, the time course of changes in the metabolic profiles of locust hemolymph that accompany phase transition was analyzed. Carnitine and its acyl derivatives, which are involved in the lipid ß-oxidation process, were identified as key differential metabolites that display robust correlation with the time courses of phase transition. RNAi silencing of two key enzymes from the carnitine system, carnitine acetyltransferase and palmitoyltransferase, resulted in a behavioral transition from the gregarious to solitarious phase and the corresponding changes of metabolic profiles. In contrast, the injection of exogenous acetylcarnitine promoted the acquisition of gregarious behavior in solitarious locusts. These results suggest that carnitines mediate locust phase transition possibly through modulating lipid metabolism and influencing the nervous system of the locusts.

Cardiac involvement in inflammatory bowel disease: role of acylcarnitine esters.

OBJECTIVES: Cardiovascular complications have been frequently described in Inflammatory Bowel Disease (IBD). Both Crohn disease and Ulcerative Colitis are characterized by malabsorption of some micronutrients, such as carnitine, which is a very important element for myocardial metabolism, being demonstrated that its deficiency correlates with heart involvement in coeliac disease. Aims of this study are to evaluate cardiac function in IBD patients asymptomatic for cardiovascular diseases and to correlate the cardiac data with the profile of carnitine esters plasma levels. MATERIALS AND METHODS: The study was carried out on 20 IBD patients by comparison with 18 sex- and age-matched clinically healthy controls. Personal and familial history, physical examination, standard electrocardiogram and echocardiogram were performed in all subjects. Complete panel of nutritional status parameters and serum levels of free carnitine and its esters were evaluated both in IBD patients and control subjects. RESULTS: Isovaleryl-carnitine, Tiglyl-carnitine, Octenoylcarnitine and Decanoyl-carnitine, were found to be significantly lower in IBD patients. Significant correlations were found between some carnitine esters and echocardiographic parameters although total and free carnitine were meanly more elevated in IBD. No statistically significant differences in echocardiographic parameters were found between IBD patients and control subjects. CONCLUSIONS: Deficiency of some isoforms of carnitine, especially those esterified with short chain fatty acids, may play an important role in cardiac involvement in course of IBD and could lead, over time, to dilated cardiomiopathy.

L-Carnitine and intestinal inflammation.

The intestinal barrier is one of the most dynamic surfaces of the body. It is here where a single layer of epithelial cells mediates the intricate encounters that occur between the host's immune system and a multitude of potential threats present in the intestinal lumen. Several key factors play an important role in the final outcome of this interaction, including the state of oxidative stress, the level of activation of the immune cells, and the integrity of the epithelial barrier. This chapter describes the main evidence demonstrating the impact that l-carnitine has on each of these factors. These findings, combined with the demonstrated safety profile of l-carnitine, underscore the potential therapeutic value of l-carnitine supplementation in humans suffering from intestinal inflammation and highlight the functional data supporting an association between Crohn's disease and mutations in the l-carnitine transporter genes.

Carnitine is necessary to maintain the phenotype and function of brown adipose tissue.

The juvenile visceral steatosis (JVS) mouse is a mutant strain with an inherited systemic carnitine deficiency. Mice of this strain show clinical signs attributable to impaired heat production and disturbed energy production. Brown adipose tissue (BAT) is the primary site of non-shivering thermogenesis in the presence of uncoupling protein-1 (UCP-1) in rodents and humans, especially in infants. To investigate the possible cause of impaired heat production in BAT, we studied the morphological features, carnitine concentration, and UCP-1 production of BAT in JVS mice. The effect of carnitine administration on these parameters was also examined. JVS mice aged 5 or 10 days (60 each) and age-matched control mice were used in this study, along with 10-day-old JVS mice treated subcutaneously with L-carnitine once a day between postpartum days 5 and 10. JVS mice showed lower body temperatures and lower concentrations of carnitine in BAT. Morphologically, BAT cells in JVS mice contained large lipid vacuoles and small mitochondria, similar to those present in white adipose tissue cells. In addition, UCP-1 mRNA and protein expression levels were significantly reduced in JVS as compared with control mice. Carnitine treatment resulted in significant increases in body temperature and carnitine concentrations in BAT, together with the recovery of normal morphological features. UCP-1 mRNA and protein expression levels were also significantly increased. These findings strongly suggest that carnitine is essential for maintaining the function and morphology of BAT.

Long-chain acylcarnitine deficiency in patients with chronic fatigue syndrome. Potential involvement of altered carnitine palmitoyltransferase-I activity.

OBJECTIVE: The underlying aetiology of chronic fatigue syndrome is currently unknown; however, in the light of carnitine's critical role in mitochondrial energy production, it has been suggested that chronic fatigue syndrome may be associated with altered carnitine homeostasis. This study was conducted to comparatively examine full endogenous carnitine profiles in patients with chronic fatigue syndrome and healthy controls. DESIGN: A cross-sectional, observational study. SETTING AND SUBJECTS: Forty-four patients with chronic fatigue syndrome and 49 age- and gender-matched healthy controls were recruited from the community and studied at the School of Pharmacy & Medical Sciences, University of South Australia. MAIN OUTCOME MEASURES: All participants completed a fatigue severity scale questionnaire and had a single fasting blood sample collected which was analysed for l-carnitine and 35 individual acylcarnitine concentrations in plasma by LC-MS/MS. RESULTS: Patients with chronic fatigue syndrome exhibited significantly altered concentrations of C8:1, C12DC, C14, C16:1, C18, C18:1, C18:2 and C18:1-OH acylcarnitines; of particular note, oleyl-L-carnitine (C18:1) and linoleyl-L-carnitine (C18:2) were, on average, 30-40% lower in patients than controls (P < 0.0001). Significant correlations between acylcarnitine concentrations and clinical symptomology were also demonstrated. CONCLUSIONS: It is proposed that this disturbance in carnitine homeostasis is reflective of a reduction in carnitine palmitoyltransferase-I (CPT-I) activity, possibly a result of the accumulation of omega-6 fatty acids previously observed in this patient population. It is hypothesized that the administration of omega-3 fatty acids in combination with l-carnitine would increase CPT-I activity and improve chronic fatigue syndrome symptomology.

Low availability of carnitine precursors as a possible reason for the diminished plasma carnitine concentrations in pregnant women.

BACKGROUND: It has been shown that plasma carnitine concentrations decrease markedly during gestation. A recent study performed with a low number of subjects suggested that this effect could be due to a low iron status which leads to an impairment of carnitine synthesis. The present study aimed to confirm this finding in a greater number of subjects. It was moreover intended to find out whether low carnitine concentrations during pregnancy could be due to a reduced availability of precursors of carnitine synthesis, namely trimethyllysine (TML) and gamma-butyrobetaine (BB). METHODS: Blood samples of 79 healthy pregnant women collected at delivery were used for this study. RESULTS: There was only a weak, non-significant (P > 0.05), correlation between plasma concentration of ferritin and those of free and total carnitine. There was no correlation between other parameters of iron status (plasma iron concentration, hemoglobin, MCV, MCH) and plasma concentration of free and total carnitine. There were, however, significant (P < 0.05) positive correlations between concentrations of TML and BB and those of free and total carnitine in plasma. CONCLUSIONS: The results of this study suggest that an insufficient iron status is not the reason for low plasma carnitine concentrations observed in pregnant women. It is rather indicated that low plasma carnitine concentrations are caused by a low availability of precursors for carnitine synthesis during gestation.

Acylcarnitines: role in brain.

l-carnitine is present in mammalian cells as free carnitine and acylcarnitines. The acylcarnitine profile has been shown to be useful in identifying inborn errors of metabolism and to be altered under different metabolic conditions. While carnitine's most widely known function is its involvement in beta-oxidation of fatty acids, it may also have other roles in metabolism. The importance of acylcarnitines in tissues with high rates of beta-oxidation such as heart and muscle is intuitive. However, acylcarnitine and carnitine supplementation have resulted in beneficial effects in the treatment of various neurological diseases, even though fat is not the major fuel for brain. Recent data indicate new, multifactorial roles for acylcarnitines in neuroprotection. Brain acylcarnitines can function in synthesizing lipids, altering and stabilizing membrane composition, modulating genes and proteins, improving mitochondrial function, increasing antioxidant activity, and enhancing cholinergic neurotransmission. Currently a relatively small subset of acylcarnitines is usually investigated. More research is needed on the use of acylcarnitines in the treatment of neurological diseases using a list of acylcarnitines encompassing a wide range of these molecules. In summary, carnitine is not merely a cofactor in beta-oxidation, but rather it has many known and yet to be discovered functions in physiology.