Hydroxylation of γ-Butyrobetaine to Carnitine in Rat Liver<sup>*</sup>

Lindstedt, Göran

doi:10.1021/bi00857a007

Cited by 113 publications

(43 citation statements)

References 65 publications

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“…The high concentration of carnitine in the rat epididymis appears to be achieved by transport from blood plasma and not local synthesis, as there is evidence that the rat epididymis does not possess the hydroxylase enzyme necessary for the conversion ofbutyrobetaine to carnitine, the final step in the biosynthetic pathway of carnitine (Casillas & Erickson, 1975a). Only the liver (with a slight capacity in the testis) appears to be capable of the final conversion step, and carnitine is then rapidly transported to other tissues (Lindstedt, 1967;Haigler & Broquist, 1974;Böhmer, 1974). Other studies have shown that the accumulation mechanism is under androgenic control (Marquis & Fritz, 1965;Brooks et al, 1973;Böhmer & Hansson, 1975;Böhmer & Johansen, 1978) and that it is influenced by circulating androgens rather than by androgens bound to the intraluminal androgen-binding protein (Böhmer et al, 1977).…”

Section: Discussionmentioning

confidence: 99%

The concentration of carnitine in the luminal fluid of the testis and epididymis of the rat and some other mammals

Hinton¹,

Snoswell²,

Setchell³

1979

Reproduction

102

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Section: Discussionmentioning

confidence: 99%

The concentration of carnitine in the luminal fluid of the testis and epididymis of the rat and some other mammals

Hinton¹,

Snoswell²,

Setchell³

1979

Reproduction

102

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“…20,21) Although g-BBD activity has been detected in kidneys from humans, cats, cows, hamsters, rabbits and Rhesus monkeys at equal or higher levels than that in the liver, the activity was not detectable or detected at very low levels in kidneys from Cebus monkeys, sheep, dogs, guinea pigs, mice and rats, in which g-BBD activity predominates in the liver. [22][23][24] In 1962, Lindstedts 25) first showed that g-BBD is stimulated considerably by 2-oxoglutarate and that the enzyme requires molecular oxygen, reduced iron (Fe 2ϩ ) and vitamin C (VC, L-ascorbic acid) for enzyme activity.…”

mentioning

confidence: 99%

“…Therefore, many studies reported the enhancement of g-BBD and TMLD activity upon the addition of VC in a dose-dependent manner using tissue extracts or partially purified enzymes. [18][19][20][21][22][26][27][28] In the absence of VC, however, g-BBD activity was detected by adding glutathione peroxidase and glutathione (GSH) to the reaction mixture, 29) although this test was not performed for TMLD.…”

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confidence: 99%

Vitamin C Is Not Essential for Carnitine Biosynthesis in Vivo: Verification in Vitamin C-Depleted Senescence Marker Protein-30/Gluconolactonase Knockout Mice

Furusawa

Sato

Tanaka

et al. 2008

Biological & Pharmaceutical Bulletin

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Carnitine is an essential cofactor in the transport of long-chain fatty acids into the mitochondrial matrix and plays an important role in energy production via b b-oxidation. Vitamin C (VC) has long been considered a requirement for the activities of two enzymes in the carnitine biosynthetic pathway, i.e., 6-N-trimethyllysine dioxygenase and g g-butyrobetaine dioxygenase. Our present study using senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which cannot synthesize VC in vivo, led to the conclusion that this notion is not true. After weaning at 40 d of age, SMP30/GNL KO mice were fed a diet lacking VC and carnitine, then given water containing 1.5 g/l VC (VC(؉) mice) or no VC (VC(؊) mice) for 75 d. Subsequently, total VC and carnitine levels were measured in the cerebrum, cerebellum, liver, kidney, soleus muscle, extensor digitorum longus muscle, heart, plasma and serum. The total VC levels in all tissues and plasma from VC(؊) SMP30/GNL KO mice were negligible, i.e., Ͻ2% of the levels in SMP30/GNL KO VC(؉) mice; however, the total carnitine levels of both groups were similar in all tissues and serum. In addition, carnitine was produced by incubated liver homogenates from the VC-depleted SMP30/GNL KO mice irrespective of the presence or absence of 1 mM VC. Collectively, these results indicate that VC is not essential for carnitine biosynthesis in vivo.

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“…Découverte dans le muscle de boeuf en 1905, sa structure a été établie en 1927 (voir Fraenkel et Friedman, 1957 temps après, on commença à entrevoir la fonction essentielle de la carnitine dans le transport des acides gras à travers la membrane mitochondriale (Fritz, 1955 Ultérieurement, on a constaté que la y-butyrobétaine est hydroxylée sur le 3e carbone. La réaction est catalysée par une y-butyrobétaine hydroxylase (Lindstedt et Lindstedt, 1961Lindstedt, , 1962Lindstedt, , 1970Lindstedt, 1967 ;Englard, Horwitz et Mills, 1978) (Mitchell, 1978). b) Les précurseurs de la carnitine.…”

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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Hydroxylation of γ-Butyrobetaine to Carnitine in Rat Liver^*

Cited by 113 publications

References 65 publications

The concentration of carnitine in the luminal fluid of the testis and epididymis of the rat and some other mammals

The concentration of carnitine in the luminal fluid of the testis and epididymis of the rat and some other mammals

Vitamin C Is Not Essential for Carnitine Biosynthesis in Vivo: Verification in Vitamin C-Depleted Senescence Marker Protein-30/Gluconolactonase Knockout Mice

Biosynthèse de la carnitine chez les mammifères

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Hydroxylation of γ-Butyrobetaine to Carnitine in Rat Liver*

Cited by 113 publications

References 65 publications

The concentration of carnitine in the luminal fluid of the testis and epididymis of the rat and some other mammals

The concentration of carnitine in the luminal fluid of the testis and epididymis of the rat and some other mammals

Vitamin C Is Not Essential for Carnitine Biosynthesis in Vivo: Verification in Vitamin C-Depleted Senescence Marker Protein-30/Gluconolactonase Knockout Mice

Biosynthèse de la carnitine chez les mammifères

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Hydroxylation of γ-Butyrobetaine to Carnitine in Rat Liver^*