scholarly journals Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport.

1984 ◽  
Vol 73 (3) ◽  
pp. 857-867 ◽  
Author(s):  
C J Rebouche ◽  
A G Engel
Keyword(s):  
Compartmental Analysis ◽  
Carnitine Deficiency ◽  
Carnitine Metabolism ◽  
Carnitine Transport

scholarly journals Carnitine Inborn Errors of Metabolism

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3251 ◽  
Author(s):  
Mohammed Almannai ◽  
Majid Alfadhel ◽  
Ayman W. El-Hattab
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Treatment Options ◽  
Carnitine Deficiency ◽  
Carnitine Palmitoyltransferase ◽  
Inborn Errors ◽  
Carnitine Transporter ◽  
Carnitine Metabolism ◽  
Carnitine Transport ◽  
Cpt I ◽  
Carnitine Palmitoyltransferase Ii

Carnitine plays essential roles in intermediary metabolism. In non-vegetarians, most of carnitine sources (~75%) are obtained from diet whereas endogenous synthesis accounts for around 25%. Renal carnitine reabsorption along with dietary intake and endogenous production maintain carnitine homeostasis. The precursors for carnitine biosynthesis are lysine and methionine. The biosynthetic pathway involves four enzymes: 6-N-trimethyllysine dioxygenase (TMLD), 3-hydroxy-6-N-trimethyllysine aldolase (HTMLA), 4-N-trimethylaminobutyraldehyde dehydrogenase (TMABADH), and γ-butyrobetaine dioxygenase (BBD). OCTN2 (organic cation/carnitine transporter novel type 2) transports carnitine into the cells. One of the major functions of carnitine is shuttling long-chain fatty acids across the mitochondrial membrane from the cytosol into the mitochondrial matrix for β-oxidation. This transport is achieved by mitochondrial carnitine–acylcarnitine cycle, which consists of three enzymes: carnitine palmitoyltransferase I (CPT I), carnitine-acylcarnitine translocase (CACT), and carnitine palmitoyltransferase II (CPT II). Carnitine inborn errors of metabolism could result from defects in carnitine biosynthesis, carnitine transport, or mitochondrial carnitine–acylcarnitine cycle. The presentation of these disorders is variable but common findings include hypoketotic hypoglycemia, cardio(myopathy), and liver disease. In this review, the metabolism and homeostasis of carnitine are discussed. Then we present details of different inborn errors of carnitine metabolism, including clinical presentation, diagnosis, and treatment options. At the end, we discuss some of the causes of secondary carnitine deficiency.

scholarly journals OCTN Cation Transporters in Health and Disease

2013 ◽  
Vol 18 (8) ◽  
pp. 851-867 ◽  
Author(s):  
Lorena Pochini ◽  
Mariafrancesca Scalise ◽  
Michele Galluccio ◽  
Cesare Indiveri
Keyword(s):  
Large Scale ◽  
Intact Cell ◽  
Organic Cation Transporter ◽  
Carnitine Deficiency ◽  
Transmembrane Segments ◽  
Pharmacological Targets ◽  
Carnitine Transport ◽  
Health And Disease ◽  
Inflammatory Bowel ◽  
Molecular Bases

The three members of the organic cation transporter novel subfamily are known to be involved in interactions with xenobiotic compounds. These proteins are characterized by 12 transmembrane segments connected by nine short loops and two large hydrophilic loops. It has been recently pointed out that acetylcholine is a physiological substrate of OCTN1. Its transport could be involved in nonneuronal cholinergic functions. OCTN2 maintains the carnitine homeostasis, resulting from intestinal absorption, distribution to tissues, and renal excretion/reabsorption. OCTN3, identified only in mouse, mediates also carnitine transport. OCTN1 and OCTN2 are associated with several pathologies, such as inflammatory bowel disease, primary carnitine deficiency, diabetes, neurological disorders, and cancer, thus representing useful pharmacological targets. The function and interaction with drugs of OCTNs have been studied in intact cell systems and in proteoliposomes. The latter experimental model enables reduced interference from other transporters or enzyme pathways. Using proteoliposomes, the molecular bases of toxicity of some drugs have recently been revealed. Therefore, proteoliposomes represent a promising experimental tool suitable for large-scale molecular screening of interactions of OCTNs with chemicals regarding human health.

Bupivacaine Inhibits Acylcarnitine Exchange in Cardiac Mitochondria

2000 ◽  
Vol 92 (2) ◽  
pp. 523-523 ◽  
Author(s):  
Guy L. Weinberg ◽  
June W. Palmer ◽  
Timothy R. VadeBoncouer ◽  
Mikko B. Zuechner ◽  
Guy Edelman ◽  
...  
Keyword(s):  
Local Anesthetics ◽  
Adenosine Diphosphate ◽  
Carnitine Deficiency ◽  
Cardiac Mitochondria ◽  
Beta Oxidation ◽  
Pyruvate Oxidation ◽  
Interfibrillar Mitochondria ◽  
Carnitine Metabolism ◽  
Acylcarnitine Translocase ◽  
Fatty Acid Beta Oxidation

Background The authors previously reported that secondary carnitine deficiency may sensitize the heart to bupivacaine-induced arrhythmias. In this study, the authors tested whether bupivacaine inhibits carnitine metabolism in cardiac mitochondria. Methods Rat cardiac interfibrillar mitochondria were prepared using a differential centrifugation technique. Rates of adenosine diphosphate-stimulated (state III) and adenosine diphosphate-limited (state IV) oxygen consumption were measured using a Clark electrode, using lipid or nonlipid substrates with varying concentrations of a local anesthetic. Results State III respiration supported by the nonlipid substrate pyruvate (plus malate) is minimally affected by bupivacaine concentrations up to 2 mM. Lower concentrations of bupivacaine inhibited respiration when the available substrates were palmitoylcarnitine or acetylcarnitine; bupivacaine concentration causing 50% reduction in respiration (IC50 +/- SD) was 0.78+/-0.17 mM and 0.37+/-0.03 mM for palmitoylcarnitine and acetylcarnitine, respectively. Respiration was equally inhibited by bupivacaine when the substrates were palmitoylcarnitine alone, or palmitoyl-CoA plus carnitine. Bupivacaine (IC50 = 0.26+/-0.06 mM) and etidocaine (IC50 = 0.30+/-0.12 mM) inhibit carnitine-stimulated pyruvate oxidation similarly, whereas the lidocaine IC50 is greater by a factor of roughly 5, (IC50 = 1.4+/-0.26 mM), and ropivacaine is intermediate, IC50 = 0.5+/-0.28 mM. Conclusions Bupivacaine inhibits mitochondrial state III respiration when acylcarnitines are the available substrate. The substrate specificity of this effect rules out bupivacaine inhibition of carnitine palmitoyl transferases I and II, carnitine acetyltransferase, and fatty acid beta-oxidation. The authors hypothesize that differential inhibition of carnitine-stimulated pyruvate oxidation by various local anesthetics supports the clinical relevance of inhibition of carnitine-acylcarnitine translocase by local anesthetics with a cardiotoxic profile.

scholarly journals Potential Role of L-Carnitine in Autism Spectrum Disorder

2021 ◽  
Vol 10 (6) ◽  
pp. 1202
Author(s):  
Alina Kępka ◽  
Agnieszka Ochocińska ◽  
Sylwia Chojnowska ◽  
Małgorzata Borzym-Kluczyk ◽  
Ewa Skorupa ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Autism Spectrum ◽  
Carnitine Deficiency ◽  
Spectrum Disorder ◽  
Respiratory Chain Complexes ◽  
Carnitine Metabolism

L-carnitine plays an important role in the functioning of the central nervous system, and especially in the mitochondrial metabolism of fatty acids. Altered carnitine metabolism, abnormal fatty acid metabolism in patients with autism spectrum disorder (ASD) has been documented. ASD is a complex heterogeneous neurodevelopmental condition that is usually diagnosed in early childhood. Patients with ASD require careful classification as this heterogeneous clinical category may include patients with an intellectual disability or high functioning, epilepsy, language impairments, or associated Mendelian genetic conditions. L-carnitine participates in the long-chain oxidation of fatty acids in the brain, stimulates acetylcholine synthesis (donor of the acyl groups), stimulates expression of growth-associated protein-43, prevents cell apoptosis and neuron damage and stimulates neurotransmission. Determination of L-carnitine in serum/plasma and analysis of acylcarnitines in a dried blood spot may be useful in ASD diagnosis and treatment. Changes in the acylcarnitine profiles may indicate potential mitochondrial dysfunctions and abnormal fatty acid metabolism in ASD children. L-carnitine deficiency or deregulation of L-carnitine metabolism in ASD is accompanied by disturbances of other metabolic pathways, e.g., Krebs cycle, the activity of respiratory chain complexes, indicative of mitochondrial dysfunction. Supplementation of L-carnitine may be beneficial to alleviate behavioral and cognitive symptoms in ASD patients.

scholarly journals Deficient Muscle Carnitine Transport in Primary Carnitine Deficiency

1997 ◽  
Vol 42 (5) ◽  
pp. 583-587 ◽  
Author(s):  
Roser Pons ◽  
Rosalba Carrozzo ◽  
Ingrid Tein ◽  
Winsome F Walker ◽  
Linda J Addonizio ◽  
...  
Keyword(s):  
Carnitine Deficiency ◽  
Carnitine Transport ◽  
Primary Carnitine Deficiency

Carnitine deficiency presenting as familial cardiomyopathy: A treatable defect in carnitine transport

1982 ◽  
Vol 101 (5) ◽  
pp. 700-705 ◽  
Author(s):  
Lewis J. Waber ◽  
David Valle ◽  
Catherine Neill ◽  
Salvatore DiMauro ◽  
Austin Shug
Keyword(s):  
Carnitine Deficiency ◽  
Carnitine Transport ◽  
Familial Cardiomyopathy
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