Studies on the biosynthesis and turnover of carnitine

Wolf, George; Berger, C.R.A.

doi:10.1016/0003-9861(61)90362-9

Cited by 71 publications

(17 citation statements)

References 14 publications

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“…It plays an essential role in fatty acid oxidation becauise fatty acids muist be esterified with carnitine in order to be transported from the cytoplasm into mitochondria, where the oxidation occuirs (1). The body's stupply of' carnitine is derived in part by ingestion of' preformed dietary carnitine, and in part b)y endogenous synthesis from the essential amino acids lysine and methionine (2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Deficiency of Carnitine in Cachectic Cirrhotic Patients

Rudman¹,

Sewell²,

Ansley³

1977

J. Clin. Invest.

172

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A 3 S T RA C T Carnitine is synthesized from lysine and metlhionine. In the rat, inade(quiate intake of either of these essential amino acids cauises carnitinie depletioIn 14 of' 36 hospitalized cirrhotics hald subnormal valtues for seruim carnitine. The creatinine/height index, midarm munscle circumference, and triceps skin-fold thickness indicated protein-calorie starvation in the 14 hypocarnitinemic liver patients. In six of the hypocarnitinemic cirrhotics (average seruim level 50% of normal), spontaneouis dietary intakes of' carnitine, lysine, and methionine were measuired and foulnd to be only 5-15% as great as in six normocarnitinemiic, healthy controls. When these six cirrhotic anuI six normnal stil)jects were given the same lysine-rich, methioninle-ricl, and carnitine-free nultritionaitl intake, the normaiitls mnain tained n oi-'matl serumiii camr iti ne levels and exeretedl 100 tLmol/day, wvhereas the cirrlhoties' sertum level fell to 25% of noimatl, and(l uirinary excretion dec ined to 15 Lmol/day. Seven lhypocarniitiniemic cirrhotics dlie(l. P'ostmlortemn concentratioons of' carnitine in liver, musele, heart, kidney, and brain averagedl only one-fouirtlh to onethir(d those in corresponding tisstues of eight normally noutrished nonhepatic patients who died after an actute illness of a 1-3-day duiration.These data show that carn-itine depletion is common in pattients hospitalized for advanced cirrhosis, and that it resuilts from three factors: stubstandard intake of dietary carnitine; substandard intake of lysine and methionine, the prectursors ftor endlogenouis carnitine synthesis; acnd loss of' cappacity to syntlhesize carnitine from lysine and methiioniine.

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Section: Introductionmentioning

confidence: 99%

Deficiency of Carnitine in Cachectic Cirrhotic Patients

Rudman¹,

Sewell²,

Ansley³

1977

J. Clin. Invest.

172

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“…Accordingly, carnitine might also be important in the case of muscle exercise, particularly under anaerobic conditions (Cerretelli and Marconi, 1988). Bremer, 1961Bremer, , 1962Wolf and Berger, 1961;Tanphaichitr et al, 1973;Hoppel, 1973a,b, 1974;Horne and Broquist, 1973). Bremer, 1961Bremer, , 1962Wolf and Berger, 1961;Tanphaichitr et al, 1973;Hoppel, 1973a,b, 1974;Horne and Broquist, 1973).…”

Section: Appendix Bmentioning

confidence: 99%

Scientific Opinion on the safety and efficacy of L-carnitine as a feed additive for all animal species based on a dossier submitted by EUROPE-ASIA Import Export GmbH

2012

EFSA Journal

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L-Carnitine has a key role in the metabolism of fatty acids as a "substrate" for the reversible acetylation of coenzyme A and as a carrier for the transport of long chain fatty acids from cytosol across the inner mitochondrial membrane. L-Carnitine administered via feed or water for drinking is considered safe for the target species. The additive appears to have a wide margin of safety (> 10) at the levels typically used (10-50 mg/kg feed). Very little information is available on the toxicology of L-carnitine. Nevertheless, based on residue data obtained from multi-fold doses of the typical use levels, the FEEDAP Panel concluded that typical supplementation of feed with L-carnitine would not substantially increase human exposure to carnitine from food of animal origin. Therefore, the FEEDAP Panel considers that the use of L-carnitine as an additive in animal nutrition is safe for the consumer. No data were provided to address user safety. In the absence of data, L-carnitine should be considered as potentially irritant to skin and eye, and as a potential skin sensitiser and inhalatory toxicant. The use of L-carnitine in animal nutrition is not expected to pose a risk to the environment. L-Carnitine was regarded as an effective source of L-carnitine in all animal species. SUMMARYFollowing a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of L-carnitine as an additive to feed and water for drinking for all animal species.L-Carnitine has a key role in the metabolism of fatty acids as a "substrate" for the reversible acetylation of coenzyme A and as a carrier for the transport of long chain fatty acids from cytosol across the inner mitochondrial membrane. Adult animals can synthesise carnitine from its precursor lysine; however, the endogenous synthesis might be insufficient in juvenile animals. Nutritional requirement data for the different animal species and categories have not been established.Oral administration routes of L-carnitine via feed or water for drinking are considered bioequivalent. L-Carnitine is safe for the target species. The additive appears to have a wide margin of safety (> 10) at the levels typically used (10-50 mg L-carnitine/kg feed).Very little information is available on the toxicology of L-carnitine. Nevertheless, based on residue data obtained from multi-fold doses of the typical use levels, the FEEDAP Panel concluded that typical supplementation of feed with L-carnitine would not substantially increase human exposure to carnitine from food of animal origin. As the absorption rate declines with increasing L-carnitine intake the endogenous carnitine pool may not significantly increase. Therefore, the FEEDAP Panel considers that the use of L-carnitine as an additive in animal nutrition is safe for the consumer.No data were provided to address user safety. In the absence of data, L -carnitine should be considered as potentially irritant to skin and eye, and...

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“…b) Les précurseurs de la carnitine. -Il a d'abord été établi que les trois groupes méthyles de la carnitine proviennent de la méthionine (Bremer, 1961 ; Berger, 1961 ; Hoppel, 1973a ; , Tanphaichitr et Broquist, 1973b , puis chez le rat (Tanphaichitr, Zaklama et Tanphaichitr et Broquist, 1973a, b ; Hoppel, 1973a), on a montré que la L-lysine était incorporée dans la carnitine : ce sont les carbones 3, 4, 5 et 6 de la lysine qui fournissent la chaîne carbonée de la carnitine, l'E-N de la lysine procurant l'azote de cette molécule (Tanphaichitr, Horne et Hoppel, 1973b ; Broquist, 1980 ;Rebouche, 1980 ; Rebouche, 1980 ;Rebouche et Engel, 1980c Kim, 1975).…”

Section: Introductionunclassified

Biosynthèse de la carnitine chez les mammifères

Bach¹

1982

Reprod. Nutr. Dévelop.

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Summary. Carnitine biosynthesis in mammals.The oxidation of long-chain fatty acids is carnitine-dependent ; these fatty acids penetrate the mitochondrion to be oxidized only when they are bound to carnitine in the form of acyl-carnitines. To meet the need for carnitine, animals depend on both exogenous supplies and endogenous synthesis. The aim of the present paper is to review our knowledge of endogenous carnitine synthesis.The precursors of carnitine are lysine and methionine but its true point of origin is trimethyllysine. This molecule is either obtained from the diet or is synthesized in the body from L-lysine (bound to protein) which is methylated 3 consecutive times by an Sadenosyl-methionine. Trimethyllysine is transformed into hydroxy-trimethyllysine, then into trimethylaminobutyraldehyde and finally into trimethylaminobutrate (or y-butyrobetaine).The y-butyrobetaine is hydroxylated into carnitine. This reaction chain only functions well when three vitamins ― ascorbic acid, pyridoxin and niacin ― are present.Studies on rat have shown that skeletal muscle, heart, intestines, testis, and especially kidneys, insure the transformation of trimethyllysine into y-butyrobetaine but that only the testis, and especially liver, can hydroxylate y-butyrobetaine into carnitine. However, in rat the relative importance of the kidneys and liver in total carnitine synthesis has not yet been determined. The situation is the same in man, although it has been proven that human brain and kidneys, as liver, have y-butyrobetaine hydroxylase. It is known that the rate of carnitine synthesis depends on three factors ― the amount of trimethyllysine available, the rate of y-butyrobetaine transfer to tissue(s) hydroxylating it and y-butyrobetaine hydroxylase activity. Moreover, it appears that carnitine synthesis is not slowed down by prolonged fasting, that it does not completely cover body needs during the first postnatal days, and that it does not decrease in two patients with systematic carnitine deficiency.Introduction.

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Studies on the biosynthesis and turnover of carnitine

Cited by 71 publications

References 14 publications

Deficiency of Carnitine in Cachectic Cirrhotic Patients

Deficiency of Carnitine in Cachectic Cirrhotic Patients

Scientific Opinion on the safety and efficacy of L-carnitine as a feed additive for all animal species based on a dossier submitted by EUROPE-ASIA Import Export GmbH

Biosynthèse de la carnitine chez les mammifères

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