Carnitine Metabolism and Its Regulation in Microorganisms and Mammals

Rebouche, Charles J.; Seim, Hermann

doi:10.1146/annurev.nutr.18.1.39

Cited by 309 publications

(260 citation statements)

References 90 publications

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“…2 However, as more and more primary structures of transporters become available, it appears impossible to infer information on the mechanism of energy coupling from sequence comparisons. For example, the galactoside-pentose-hexuronide family (Transport Protein Database TC 2.A.…”

Section: Discussionmentioning

confidence: 99%

“…For example, the galactoside-pentose-hexuronide family (Transport Protein Database TC 2.A. 2) 3 is a mixed family containing proteins capable of catalyzing symport and/or antiport processes (43).…”

Section: Discussionmentioning

confidence: 99%

“…L-Carnitine (R-(Ϫ)-3-hydroxy-4-trimethylaminobutyrate) is essential for transport of activated fatty acids across the inner mitochondrial membrane via the carnitine/acylcarnitine exchange protein (1,2). Bacteria use L-carnitine in different ways (3).…”

mentioning

confidence: 99%

“…They form a small family of transporters, the betaine/carnitine/ choline transporter (BCCT) 1 family (Transport Protein Database TC 2.A.15). 2 Proteins of this family share the common functional feature of transporting molecules with a quaternary ammonium group (R-N ϩ (CH 3 ) 3 ). Some of these transporters have been shown to utilize electrochemical ion gradients (H ϩ , Na ϩ ) for substrate accumulation.…”

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confidence: 99%

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CaiT of Escherichia coli, a New Transporter Catalyzing l-Carnitine/γ-Butyrobetaine Exchange

Jung

Buchholz

Clausen³

et al. 2002

Journal of Biological Chemistry

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L-Carnitine is essential for ␤-oxidation of fatty acids in mitochondria. Bacterial metabolic pathways are used for the production of this medically important compound. Here, we report the first detailed functional characterization of the caiT gene product, a putative transport protein whose function is required for L-carnitine conversion in Escherichia coli. The caiT gene was overexpressed in E. coli, and the gene product was purified by affinity chromatography and reconstituted into proteoliposomes. Functional analyses with intact cells and proteoliposomes demonstrated that CaiT is able to catalyze the exchange of L-carnitine for ␥-butyrobetaine, the excreted end product of L-carnitine conversion in E. coli, and related betaines. Electrochemical ion gradients did not significantly stimulate L-carnitine uptake. Analysis of L-carnitine counterflow yielded an apparent external K m of 105 M and a turnover number of 5.5 s ؊1 . Contrary to related proteins, CaiT activity was not modulated by osmotic stress. L-Carnitine binding to CaiT increased the protein fluorescence and caused a red shift in the emission maximum, an observation explained by ligand-induced conformational alterations. The fluorescence effect was specific for betaine structures, for which the distance between trimethylammonium and carboxyl groups proved to be crucial for affinity. Taken together, the results suggest that CaiT functions as an exchanger (antiporter) for L-carnitine and ␥-butyrobetaine according to the substrate/product antiport principle.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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CaiT of Escherichia coli, a New Transporter Catalyzing l-Carnitine/γ-Butyrobetaine Exchange

Jung

Buchholz

Clausen³

et al. 2002

Journal of Biological Chemistry

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“…Carnitine is obtained mostly from the diet. It can also be synthesized endogenously by skeletal muscle, heart, liver, kidney and brain from the essential amino acids lysine and methionine (Rebouche and Seim, 1998).…”

Section: Introductionmentioning

confidence: 99%

Impact of L-Carnitine on Bisphenol A-Induced Kidney Damage in Rats

Edres¹,

Taha²,

Mandour³

et al. 2018

AJVS

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Key words:Bisphenol A, L-carnitine, Malondialdehyde, Hydronephrosis, GlutathioneThe present study aimed to explore the protective effects of L-carnitine on the oxidative stress induced by Bisphenol A (BPA) in rat kidneys. Forty male adult rats were allocated into four groups (10 rats each); placebo, BPA (50 mg/kg bwt per os), Lcarnitine (500 mg/kg bwt i.p), and the BPA/L-carnitine-treated group. After 70 days, blood and kidneys were collected for measurement of renal function, oxidative/antioxidative status, histopathological analyses, and gene expression of nrf2. BPA significantly increased serum urea and carnitine levels suggesting renal damage evidenced by hydropic degenerative changes and hydronephrosis. The level of malondialdehyde (MDA) in kidney was elevated along with decline in renal total antioxidant capacity (TAC) and reduced glutathione (GSH) concentrations following challenged with BPA. Notably, the expression of nrf2 mRNA transcript in kidney tissues was down-regulated after BPA-induced toxicity. L-carnitine treatment ameliorates the damaged effects of BPA on kidneys as indicated by low levels of serum urea and carnitine, and renal MDA. Further, L-carnitine enhances the antioxidants (TAC, and GSH), with up-regulation of nrf2 expression in kidney tissues. Our results suggest the renoprotective activity of L-carnitine in BPA-induced kidney injuries through induction of antioxidant system and modulation of oxidative stress.

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Cancer and anticancer therapy-induced modifications on metabolism mediated by carnitine system

et al. 2000

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An efficient regulation of fuel metabolism in response to internal and environmental stimuli is a vital task that requires an intact carnitine system. The carnitine system, comprehensive of carnitine, its derivatives, and proteins involved in its transformation and transport, is indispensable for glucose and lipid metabolism in cells. Two major functions have been identified for the carnitine system: (1) to facilitate entry of long-chain fatty acids into mitochondria for their utilization in energy-generating processes; (2) to facilitate removal from mitochondria of short-chain and medium-chain fatty acids that accumulate as a result of normal and abnormal metabolism. In cancer patients, abnormalities of tumor tissue as well as nontumor tissue metabolism have been observed. Such abnormalities are supposed to contribute to deterioration of clinical status of patients, or might induce cancerogenesis by themselves. The carnitine system appears abnormally expressed both in tumor tissue, in such a way as to greatly reduce fatty acid beta-oxidation, and in nontumor tissue. In this view, the study of the carnitine system represents a tool to understand the molecular basis underlying the metabolism in normal and cancer cells. Some important anticancer drugs contribute to dysfunction of the carnitine system in nontumor tissues, which is reversed by carnitine treatment, without affecting anticancer therapeutic efficacy. In conclusion, a more complex approach to mechanisms that underlie tumor growth, which takes into account the altered metabolic pathways in cancer disease, could represent a challenge for the future of cancer research.

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Carnitine Metabolism and Its Regulation in Microorganisms and Mammals

Cited by 309 publications

References 90 publications

CaiT of Escherichia coli, a New Transporter Catalyzing l-Carnitine/γ-Butyrobetaine Exchange

CaiT of Escherichia coli, a New Transporter Catalyzing l-Carnitine/γ-Butyrobetaine Exchange

Impact of L-Carnitine on Bisphenol A-Induced Kidney Damage in Rats

Cancer and anticancer therapy-induced modifications on metabolism mediated by carnitine system

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