Metabolic Fate of Dietary Carnitine in Human Adults: Identification and Quantification of Urinary and Fecal Metabolites

Rebouche, Charles J.; Chenard, Catherine A.

doi:10.1093/jn/121.4.539

Cited by 129 publications

(90 citation statements)

References 15 publications

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“…The amount of protein in supernatant was measured according to [16] using bovine serum albumin as standard. Malondialdehyde (MDA) was measured according to [Maron,1979].…”

Section: Assay Of Inflammatory Cytokines Levels Of Il-6 Tnf- Malondmentioning

confidence: 99%

Protective Role of Carnitine Synergized With Vitamin E Against Isoproterenol Induced Cardiac Infarction in Rats.

Huwait¹,

Al-Ghamdi²

2017

Afr J Tradit Complement Altern Med

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“…The amount of protein in supernatant was measured according to [16] using bovine serum albumin as standard. Malondialdehyde (MDA) was measured according to [Maron,1979].…”

Section: Assay Of Inflammatory Cytokines Levels Of Il-6 Tnf- Malondmentioning

confidence: 99%

Protective Role of Carnitine Synergized With Vitamin E Against Isoproterenol Induced Cardiac Infarction in Rats.

Huwait¹,

Al-Ghamdi²

2017

Afr J Tradit Complement Altern Med

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“…Although carnitine can be acquired through endogenous biosynthesis, our daily demand is largely met through dietary intake from carnitine-containing food (26). It is known that a significant proportion of dietary carnitine can be further metabolized by microbiota before absorption (20,27). This microbial-mediated metabolic pathway not only diverts carnitine away from the host, causing conditional carnitine deficiency in certain human populations, but promotes TMAO formation and subsequent increased risk of atherosclerosis (20,21).…”

mentioning

confidence: 99%

Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota

Zhu¹,

Jameson²,

Crosatti

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

275

312

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Dietary intake of L-carnitine can promote cardiovascular diseases in humans through microbial production of trimethylamine (TMA) and its subsequent oxidation to trimethylamine N-oxide by hepatic flavin-containing monooxygenases. Although our microbiota are responsible for TMA formation from carnitine, the underpinning molecular and biochemical mechanisms remain unclear. In this study, using bioinformatics approaches, we first identified a two-component Rieske-type oxygenase/reductase (CntAB) and associated gene cluster proposed to be involved in carnitine metabolism in representative genomes of the human microbiota. CntA belongs to a group of previously uncharacterized Rieske-type proteins and has an unusual "bridging" glutamate but not the aspartate residue, which is believed to facilitate intersubunit electron transfer between the Rieske center and the catalytic mononuclear iron center. Using Acinetobacter baumannii as the model, we then demonstrate that cntAB is essential in carnitine degradation to TMA. Heterologous overexpression of cntAB enables Escherichia coli to produce TMA, confirming that these genes are sufficient in TMA formation. Site-directed mutagenesis experiments have confirmed that this unusual "bridging glutamate" residue in CntA is essential in catalysis and neither mutant (E205D, E205A) is able to produce TMA. Taken together, the data in our study reveal the molecular and biochemical mechanisms underpinning carnitine metabolism to TMA in human microbiota and assign the role of this novel group of Rieske-type proteins in microbial carnitine metabolism. methylated amine metabolism | comparative genomics | gut microbiota

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“…In several observational studies, it was noted that individuals on high carnitine diets (Ͼ6 grams) had approximately 5-15% absorption, while those on a low load diet of carnitine (Ͻ1 g), such as a vegan diet, had greater than 75% of the carnitine absorbed [52,90,91]. This apparent limit in absorptive capacity may limit the clinical effects on an overdose of oral L-carnitine.…”

Section: Is L-carnitine Safe?mentioning

confidence: 99%

Case files of the Children’s Hospital of Michigan Regional Poison Control Center: The use of carnitine for the management of acute valproic acid toxicity

Katiyar

Aaron

2007

J. Med. Toxicol.

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A 28-year-old African-American male was found unresponsive outside of his girlfriend's house around 7 o'clock in the morning. He spent the night at the girlfriend's house and was last witnessed to be awake about 12 hours earlier. The girlfriend and her family were unable to awaken the patient and called emergency medical services (EMS). There was no history of headache, dizziness, fever, chills, nausea, vomiting, seizures, trauma, depressive thoughts, or suicidal ideation. When EMS arrived, they administered 6 mg of naloxone intramuscularly without effect, and the patient was transported to the emergency department (ED).After arriving in the ED, the cardiac monitor displayed a narrow-complex rhythm with a rate of 85-90 per minute. His initial vital signs were: heart rate 91/min; blood pressure 148/80 mmHg; respiratory rate 24/min; temperature 35.1°C (95.1°F) rectally; and pulse oximetry 100% on non-rebreather face mask oxygen. A fingerstick glucose determination was 106 mg/dL.Physical examination revealed a well developed, well nourished individual who was obtunded and unresponsive. His pupils were 2 mm, unreactive to light, and without nystagmus. He had diffuse bilateral wheezing, regular heart rate without any murmurs, and decreased bowel sounds. The patient had warm skin with good distal pulses in all extremities and no cyanosis, erythema, or edema. There was no clonus or hyperreflexia, and the gag reflex was intact.His past medical history was only pertinent for an old gunshot wound to the head. He developed a seizure disorder and was taking divalproex, 500 mg BID. Reportedly, he was allergic to carbamazepine and phenytoin. The patient smoked cigarettes, but the family stated that he had no history of alcohol or illicit drug use.A 12-lead electrocardiogram showed a sinus rhythm with a rate of 92 bpm, a PR interval of 134 msec, a QRS duration of 90 msec, and a QTc of 601 msec. A head CT and chest radiograph were unremarkable. Laboratory tests were obtained.

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Metabolic Fate of Dietary Carnitine in Human Adults: Identification and Quantification of Urinary and Fecal Metabolites

Cited by 129 publications

References 15 publications

Protective Role of Carnitine Synergized With Vitamin E Against Isoproterenol Induced Cardiac Infarction in Rats.

Protective Role of Carnitine Synergized With Vitamin E Against Isoproterenol Induced Cardiac Infarction in Rats.

Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota

Case files of the Children’s Hospital of Michigan Regional Poison Control Center: The use of carnitine for the management of acute valproic acid toxicity

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