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PubMedDate not supplied

Choline and vitamin B12 deficiencies are interrelated in folate-replete long-term total parenteral nutrition patients.

BACKGROUND: Choline has recently been recognized as an essential nutrient, in part based on deficiency data in long-term home total parenteral nutrition (TPN) patients. Choline, a methyl donor in the metabolism of homocysteine, is intricately related to folate status, but little is known about choline and vitamin B12 status. Long-term TPN patients are also subject to vitamin B12 deficiency. OBJECTIVE: The objective of the study was to evaluate any interaction between choline, vitamin B12, and folate in patients with severe malabsorption syndromes, requiring long-term TPN. DESIGN: Plasma free choline, serum and red blood cell (RBC) folate, serum vitamin B12 methylmalonic acid, B6, and plasma total homocysteine concentrations were assayed by standard methods. Low choline was defined as values that fall 1 to < or =3 and marked low choline concentration as >3 SD below the control mean. RESULTS: Both low choline concentrations (52% were marked low, 33% low, 14% normal) and elevated methylmalonic acid concentrations (47%) were prevalent. Choline concentration was significantly lower and RBC folate higher in patients with elevated methylmalonic acid. Total homocysteine elevations were rare (3 of 21) and mild. CONCLUSIONS: These data suggest a strong interaction between vitamin B12 and choline deficiencies and folate status in this population, which may be due in part to variations in vitamin and choline delivery by TPN. Folate adequacy may increase B12 use for homocysteine metabolism, thus limiting B12 availability for methylmaIonic acid metabolism. Choline use may also increase, and choline deficiency may worsen if choline substitutes when the vitamin B12 side of the homocysteine metabolic pathway cannot be used.

Choline↗
PubMed1992

1-beta-D-arabinofuranosylcytosine-diphosphate-choline is formed by the reversal of cholinephosphotransferase and not via cytidylyltransferase.

In an effort to identify the pathway leading to the formation of 1-beta-D-arabinofuranosylcytosine-diphosphate (ara-CDP)-choline from 1-beta-D-arabinofuranosylcytosine (ara-C) treatment of cultured cells, as well as of cells obtained from leukemia patients, we probed the enzymatic steps involved in the CDP-choline pathway for phosphatidylcholine biosynthesis. Ara-C-triphosphate was not a substrate for CTP:phosphocholine cytidylyltransferase activity under the conditions employed, whereas CTP and dCTP were utilized to form CDP-choline and dCDP-choline, respectively. When presented together, ara-C-triphosphate and CTP inhibited the enzymatic conversion of CTP to CDP-choline in the presence of phosphocholine, with a Ki of 6 mM. Since CTP:phosphocholine cytidylyltransferase did not appear to be responsible for the increased levels of ara-CDP-choline, we next studied the other enzyme in the pathway for phosphatidylcholine synthesis that could form ara-CDP-choline, CDP-choline:1,2-diacylglycerol cholinephosphotransferase. CDP-choline:1,2-diacylglycerol cholinephosphotransferase activity present in microsomes isolated from L5178Y murine leukemia cells exhibited a reversal of its normal catalytic activity, using CMP and 1-beta-D-arabinofuranosylcytosine-monophosphate (ara-CMP) along with phosphatidylcholine to produce either CDP-choline or ara-CDP-choline, plus diradylglycerol. The Vmax and Km values for CMP were 0.78 +/- 0.04 nmol/min/mg and 340 +/- 20 microM, respectively, whereas the Vmax and Km for ara-CMP were 0.22 +/- 0.06 nmol/min/mg and 1410 +/- 540 microM, respectively. A Ki value of 3 mM was obtained for ara-CMP under the cell-free assay conditions used. These results indicate that ara-CDP-choline most likely arises from a reversal of the CDP-choline:1,2-diacylglycerol cholinephosphotransferase utilizing ara-CMP, rather than from the catalysis of ara-C-triphosphate plus phosphocholine to ara-CDP-choline by CTP:phosphocholine cytidylyltransferase. It is speculated that this mechanism may explain, in part, the rapid cellular lysis observed with high dose ara-C therapy.

Animals↗
PubMed1988

Ethanolamine and choline transport in cultured bovine aortic endothelial cells.

The transport of the polar head groups, ethanolamine and choline, was examined in cultured bovine aortic endothelial cells. Both ethanolamine and choline are taken up by high- and low-affinity systems. The K'm and V'max for the Na+-dependent, high-affinity ethanolamine and choline transport system are 3.0 and 3.0 microM and 5.4 and 7.3 pmol/mg protein/min, respectively. Ethanolamine and choline competitively influence one another's transport as the presence of 50 microM ethanolamine increases the K'm but not the V'max of choline uptake. Likewise, 50 microM choline increases the K'm but not the V'max of ethanolamine transport. The concentration of ethanolamine that inhibits maximal velocity of 5 microM choline by 50% is 9.7 microM, while 12 microM choline inhibits 5 microM ethanolamine maximal velocity by 50%. Uptake of both head groups is only partially Na+-dependent and is inhibited similarly by 2-methylethanolamine and 2,2-dimethylethanolamine at all concentrations examined. Hemicholinium-3, a classic inhibitor of high-affinity, Na+-dependent choline transport, reduces both ethanolamine and choline accumulation in a concentration-dependent fashion, but has a greater effect on choline transport at higher concentrations. The major portion of these data is consistent with our hypothesis that the uptake of physiological concentrations of ethanolamine and choline may occur through the same transport system. However, the results of the effect of hemicholinium-3 and the extent of Na+-dependency of choline and ethanolamine uptake could be interpreted as meaning that separate transport systems for choline and ethanolamine exist which cross react or that a single transport system exists which has separate active sites for the two compounds.

Animals↗
PubMed1987

Choline and acetylcholine metabolism in slice cultures of the newborn rat septum.

The incorporation of [3H]choline into acetylcholine and other choline-containing compounds was investigated in slice cultures of the septal area of newborn rats. At choline concentrations in the range of the high affinity transport mechanism (0.1-1 microM) most of the labeled choline was incorporated into phosphorylcholine, followed by lipids, acetylcholine and the free choline pool. Hemicholinium-3 (1-10 microM) lead to a marked decrease of acetylcholine synthesis, whereas choline accumulation or phosphorylcholine synthesis were not decreased. Both basal and K+-induced release of acetylcholine were Ca2+ dependent. The efflux of choline was not stimulated by high K+. When choline was absent from the incubation medium, the slices were able to liberate significant amounts of the [3H]choline previously incorporated into phospholipids, and were also able to synthesize some acetylcholine. In choline-free medium, acetylcholine synthesis was greatly enhanced by depolarization. During the period in culture, there was a decrease of the incorporation rate of [3H]choline into phosphorylcholine and an increase of the incorporation rate into acetylcholine. The tissue structure was well preserved after several weeks in culture. After staining for acetylcholinesterase, the cholinergic neurons in the cultures showed a similar morphology to that seen in situ. The main conclusions of the present study are: cholinergic neurons in slice cultures develop and behave in a manner which is very similar to their in situ counterparts; the main divergence from previous studies of choline metabolism in tissue culture is the substantial incorporation rate of choline into acetylcholine at choline concentrations in the range of the high affinity uptake mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1981

Profound effects of combining choline and piracetam on memory enhancement and cholinergic function in aged rats.

In an attempt to gain some insight into possible approaches to reducing age-related memory disturbances, aged Fischer 344 rats were administered either vehicle, choline, piracetam or a combination of choline or piracetam. Animals in each group were tested behaviorally for retention of a one trial passive avoidance task, and biochemically to determine changes in choline and acetylcholine levels in hippocampus, cortex and striatum. Previous research has shown that rats of this strain suffer severe age-related deficits on this passive avoidance task and that memory disturbances are at least partially responsible. Those subjects given only choline (100 mg/kg) did not differ on the behavioral task from control animals administered vehicle. Rats given piracetam (100 mg/kg) performed slightly better than control rats (p less than 0.05), but rats given the piracetam/choline combination (100 mg/kg of each) exhibited retention scores several times better than those given piracetam alone. In a second study, it was shown that twice the dose of piracetam (200 mg/kg) or choline (200 mg/kg) alone, still did not enhance retention nearly as well as when piracetam and choline (100 mg/kg of each) were administered together. Further, repeated administration (1 week) of the piracetam/choline combination was superior to acute injections. Regional determinations of choline and acetylcholine revealed interesting differences between treatments and brain area. Although choline administration raised choline content about 50% in striatum and cortex, changes in acetylcholine levels were much more subtle (only 6-10%). No significant changes following choline administration were observed in the hippocampus. However, piracetam alone markedly increased choline content in hippocampus (88%) and tended to decrease acetylcholine levels (19%). No measurable changes in striatum or cortex were observed following piracetam administration. The combination of choline and piracetam did not potentiate the effects seen with either drug alone, and in certain cases the effects were much less pronounced under the drug combination. These data are discussed as they relate to possible effects of choline and piracetam on cholinergic transmission and other neuronal function, and how these effects may reduce specific memory disturbances in aged subjects. The results of these studies demonstrate that the effects of combining choline and piracetam are quite different than those obtained with either drug alone and support the notion that in order to achieve substantial efficacy in aged subjects it may be necessary to reduce multiple, interactive neurochemical dysfunctions in the brain, or affect activity in more than one parameter of a deficient metabolic pathway.

Acetylcholine↗
PubMedDate not supplied

Human red blood cell choline uptake with age and Alzheimer's disease.

Since previous studies suggested that blood choline homeostasis is altered in aging and in Alzheimer's disease, choline uptake was examined in human red blood cells (RBC) from young adults, intellectually-intact elderly controls and outpatients with Alzheimer's disease. Eadie-Hofstee analysis of uptake by RBC from young controls indicated two components; thus, group comparisons were done with 1 and 50 microM choline in the media. Temperature-dependent choline uptake at low and high choline concentrations increased in RBC from elderly controls (62-66%) or Alzheimer patients (52-54%) compared to young controls. These changes in transport were not directly related to altered RBC choline content, since RBC choline concentrations did not vary significantly between groups. However, plasma choline content was significantly elevated in elderly controls and Alzheimer patients compared to young control values. The RBC to plasma ratio of choline was reduced in elderly compared to young controls, whereas the ratio in Alzheimer patients was between the two other groups. Thus, abnormalities in RBC choline uptake and plasma choline content were not exacerbated in Alzheimer patients, and these results do not support suggestions that Alzheimer's disease is a form of generalized accelerated aging. The striking changes in RBC choline uptake and plasma choline content in elderly subjects do indicate age-related changes in systemic choline homeostasis and these abnormalities may contribute to the predisposition of the elderly to neurological diseases.

Adult↗
PubMed2006

Reduced expression and capacity of the striatal high-affinity choline transporter in hyperdopaminergic mice.

Behavioral and neuronal abnormalities observed in mice exhibiting a reduced expression of the dopamine transporter model important aspects of schizophrenia, addiction, and attentional disorders. As the consequences of a chronic hyperdopaminergic tone for striatal output regulation have remained poorly understood, the present experiments were designed to determine the status of striatal interneuronal cholinergic neurotransmission in dopamine transporter knockdown animals. The high-affinity choline transporter represents the rate-limiting step of acetylcholine synthesis and release. Compared with wild type mice, striatal high-affinity choline transporter expression in dopamine transporter knockdown mice was significantly decreased. As in vivo basal striatal acetylcholine release did not differ between the strains, reduced high-affinity choline transporter expression in dopamine transporter knockdown mice was not due to reduced basal cholinergic activity. Furthermore, the proportion of high-affinity choline transporters expressed in plasma membrane-enriched versus vesicular membrane-enriched fractions did not differ from wild type animals, suggesting that changes in intracellular high-affinity choline transporter trafficking were not associated with lower overall levels of striatal high-affinity choline transporters. Synaptosomal choline uptake assays indicated a reduced capacity of striatal high-affinity choline transporters in dopamine transporter knockdown mice, and thus the functional significance of the reduced level of high-affinity choline transporter expression. Likewise, in vivo measures of the capacity of striatal high-affinity choline transporters to clear increases in extracellular choline concentrations, using choline-sensitive microelectrodes, revealed a 37-41% reduction in hemicholinium-sensitive clearance of exogenous choline in dopamine transporter knockdown mice. Furthermore, clearance of potassium-evoked choline signals was reduced in dopamine transporter knockdown mice (1.63+/-0.15 microM/s) compared with wild type animals (2.29+/-0.21 microM/s). Dysregulated striatal cholinergic neurotransmission is hypothesized to disrupt the integration of thalamic and cortical information at spiny projection neurons and thus to contribute to abnormal striatal information processing in dopamine transporter knockdown mice.

Acetylcholine↗
PubMed1988

Uptake of choline by rat mammary-gland epithelial cells.

The neonatal mammal requires especially large amounts of choline to sustain growth. Much of this choline is derived from the newborn's only source of food, milk. The concentration of choline in rat milk [182 +/- 24 microM (S.E.M.)] was much higher than that in maternal serum (11.6 +/- 0.9 microM), suggesting that a mechanism capable of concentrating choline into milk must exist. We characterized choline uptake by mammary epithelial cells (the site of milk production) of the lactating rat. We observed two uptake processes, one saturable and obeying Michaelis-Menten kinetics, and the other non-saturable and linear. At physiological blood choline concentrations, the saturable component of choline uptake predominated. The saturable component had Kapp. = 35 +/- 16 microM, and Vmax. = 1.24 +/- 0.19 nmol/h per mg of protein. Saturable uptake of choline was inhibited by hemicholinium-3. Ca2+ was required for uptake, but Mg2+ was not. Replacement Na+ with K+, Li+ or sucrose inhibited transport. Ouabain did not inhibit choline uptake. Choline concentration in epithelial cells was 67.7 +/- 1.9 nmol/g wet wt. at the start of incubation at 37 degrees C and rose to 80.9 +/- 6.5 nmol/g wet wt. over 30 min. Much of the choline accumulated by the mammary gland (in the presence of endogenous concentrations of choline) remained in the form of choline (50 +/- 1.2%), phosphatidylcholine (12 +/- 2.3%), lysophosphatidylcholine (0.1 +/- 0.03%), betaine (7 +/- 0.3% and phosphocholine (6 +/- 0.5%). In addition, we isolated 25 +/- 1.2% of choline-derived radiolabel in an unidentified compound.

2,4-Dinitrophenol↗
PubMed1976

Synthesis of choline from ethanolamine in rat brain.

Specific radioactivities of choline, acetylcholine, phosphocholine, lecithin, lysolecithin, and glycerophosphorylcholine have been measured in brain, blood, liver, and muscle after the intravenous injection of three labeled precursors: choline, methyl-labeled methionine, and ethanolamine. In relation to the specific activity of free choline in blood there was significantly more radioactivity in the free choline of brain after administration of methyl-labeled methionine and labeled ethanolamine than after labeled choline. Since the choline moiety of lipids, which returns back to the choline pool, contained less radioactivity after methyl-labeled methionine and labeled ethanolamine than after labeled choline, it is the most likely interpretation of the finding that choline, in brain can be formed by methylation of free ethanolamine. Data from liver confirm that lecithin is formed in the liver by methylation of phosphatidylethanolamine. No indication was found for the synthesis of choline in muscle. Rates of transfer and transport of choline in brain have been calculated as nmol x g-1 x min-1 as follows: turnover rate of choline, 36.5; rate of synthesis of choline by methylation and net loss of choline into the bloodstream, 6.3; inflow from the blood 6.2; outflow into the blood, 12.5; transfer into lipids and vice versa, 20; transfer to acetylcholine and vice versa, 4.

Acetylcholine↗
PubMed1999

Phosphorylation and regulation of choline kinase from Saccharomyces cerevisiae by protein kinase A.

The CKI1-encoded choline kinase (ATP:choline phosphotransferase, EC 2.7.1.32) from Saccharomyces cerevisiae was phosphorylated in vivo on multiple serine residues. Activation of protein kinase A activity in vivo resulted in a transient increase in the phosphorylation of choline kinase. This phosphorylation was accompanied by a stimulation in choline kinase activity. In vitro, protein kinase A phosphorylated choline kinase on a serine residue with a stoichiometry (0.44 mol of phosphate/mol of choline kinase) consistent with one phosphorylation site/choline kinase subunit. The major phosphopeptide derived from the enzyme phosphorylated in vitro by protein kinase A was common to one of the major phosphopeptides derived from the enzyme phosphorylated in vivo. Protein kinase A activity was dose- and time-dependent and dependent on the concentrations of ATP (Km 2.1 microM) and choline kinase (Km 0.12 microM). Phosphorylation of choline kinase with protein kinase A resulted in a stimulation (1.9-fold) in choline kinase activity whereas alkaline phosphatase treatment of choline kinase resulted in a 60% decrease in choline kinase activity. The mechanism of the protein kinase A-mediated stimulation in choline kinase activity involved an increase in the apparent Vmax values with respect to ATP (2.6-fold) and choline (2.7-fold). Overall, the results reported here were consistent with the conclusion that choline kinase was regulated by protein kinase A phosphorylation.

Alkaline Phosphatase↗
PubMed1971

Assembly of lipids into membranes in Acanthamoeba palestinensis. I. Observations on the specificity and stability of choline- 14 C and glycerol- 3 H as labels for membrane phospholipids.

In order to determine the feasibility of using radioactive precursors as markers for membrane phospholipids in Acanthamoeba palestinensis, the characteristics of phospholipids labeled with choline-(14)C and glycerol-(3)H were examined. Choline-(14)C was found to be a specific label for phosphatidyl choline. There was a turnover of the radioactive moiety of phosphatidyl choline at a rate that varied with the concentration of nonradioactive choline added to the growth medium. Radioactivity was lost from labeled phosphatidyl choline into the acid-soluble intracellular pool and from the pool into the extracellular medium. This loss of radioactivity from cells leveled off and an equilibrium was reached between the label in the cells and in the medium. Radioactive choline was incorporated into phosphatidyl choline by cell-free microsomal suspensions. This incorporation leveled off with the attainment of an equilibrium between the choline-(14)C in the reaction mixture and the choline-(14)C moiety of phosphatidyl choline in the microsomal membranes. Therefore, a choline exchange reaction may occur in cell-free membranes, as well as living A. palestinensis. In contrast to choline-(14)C, the apparent turnover of glycerol-(3)H-labeled phospholipids was not affected by large concentrations of nonradioactive choline or glycerol in the medium. The radioactivity in lipids labeled with glycerol-(3)H consisted of 33% neutral lipids and 67% phospholipids. Phospholipids labeled with glycerol-(3)H turned over slowly, with a concomitant increase in the percentage of label in neutral lipids, indicating a conversion of phospholipids to neutral lipids. Because most ( approximately 96%) of the glycerol-(3)H recovered from microsomal membranes was in phospholipids, whereas only a minor component ( approximately 2%) of the glycerol-(3)H was in the phospholipids isolated from nonmembrane lipids, glycerol-(3)H was judged to be a specific marker for membrane phospholipids.

Amoeba↗
PubMed2004

Elevated serum creatine phosphokinase in choline-deficient humans: mechanistic studies in C2C12 mouse myoblasts.

BACKGROUND: Choline is a required nutrient, and humans deprived of choline develop liver damage. OBJECTIVE: This study examined the effect of choline deficiency on muscle cells and the release of creatine phosphokinase (CPK) as a sequela of that deficiency. DESIGN: Four men were fed diets containing adequate and deficient amounts of choline, and serum was collected at intervals for measurement of CPK. C2C12 mouse myoblasts were cultured in a defined medium containing 0 or 70 micromol choline/L for up to 96 h, and CPK was measured in the media; choline and metabolites were measured in cells. Apoptosis was assessed by using terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling and activated caspase-3 immunohistochemistry. Cell fragility in response to hypo-osmotic stress was also assessed. RESULTS: Three of 4 humans fed a choline-deficient diet had significantly elevated serum CPK activity derived from skeletal muscle (up to 66-fold; P < 0.01) that resolved when choline was restored to their diets. Cells grown in choline-deficient medium for 72 h leaked 3.5-fold more CPK than did cells grown in medium with 70 micromol choline/L (control medium; P < 0.01). Apoptosis was induced in cells grown in choline-deficient medium. Phosphatidylcholine concentrations were diminished in choline-deficient cells (to 43% of concentrations in control cells at 72 h; P < 0.01), as were concentrations of intracellular choline, phosphocholine, and glycerophosphocholine. Cells grown in choline-deficient medium had greater membrane osmotic fragility than did cells grown in control medium. CONCLUSIONS: Choline deficiency results in diminished concentrations of membrane phosphatidylcholine in myocytes, which makes them more fragile and results in increased leakage of CPK from cells. Serum CPK may be a useful clinical marker for choline deficiency in humans.

Adult↗
PubMed1985

The effect of lithium on choline transport in human erythrocytes.

Erythrocytes from lithium treated patients were separated according to the time they had been circulating in the plasma. Choline transport and choline content were measured in the erythrocyte fractions separated according to age, in order to investigate the relationship between decreased choline transport and increased choline content seen in lithium treated patients. The most recently formed erythrocytes of normal subjects had the greatest choline content and the most active choline carrier. The erythrocytes of lithium treated patients had reduced choline carrier activity and increased choline content in all age bands. However the greatest accumulation of choline and least inhibited choline carrier activity was seen in the most recently formed cells. The alteration in phospholipid concentrations measured could not of themselves account for elevated erythrocyte choline levels seen in lithium treated patients. It is concluded that the increase in choline content levels in lithiated erythrocytes does not have a simple inverse relationship with the deficiency in choline transport. The inhibition of the choline carrier is caused by modification due to circulation in lithiated plasma rather than a lack of its synthesis in reticulocytes.

Choline↗
PubMed1987

Intestinal absorption of choline in rats.

The intestinal absorption of choline, an endogenous quaternary ammonium, from the rat jejunum has been investigated with an in situ ligated loop method and an in vitro everted sac method. Choline was absorbed rapidly from the ligated jejunum and structural analogs inhibited choline absorption competitively. In in vitro experiments, choline was transported from the mucosal fluid to the intracellular fluid against a concentration gradient and the rate of tissue uptake was highly affected by incubation temperature, aerobic condition and the presence of a metabolic inhibitor, 2,4-dinitrophenol. The tissue accumulation of choline was saturable at concentrations below 100 microM and, above this concentration the uptake ratio of choline (medium to tissue) was almost constant. One mM hemicholinium-3, which is well known to inhibit choline uptake by neurons through the choline specific carrier, also significantly inhibited choline uptake, especially at concentrations of choline below 100 microM. The fact that the choline uptake is linear in the presence of hemicholinium-3 shows that choline is partially absorbed by passive diffusion. The difference between the total tissue accumulation and choline uptake by the passive diffusional pathway followed Michaelis-Menten kinetics and the apparent Kt of 47 microM and Vmax of 4.1 nmol/ml intracellular fluid/min were determined by an in vitro everted sac method. These findings suggested that, a lower concentrations, choline was absorbed from the rat intestine mainly by an active transport system.

Animals↗
PubMed1986

Synthesis of phosphatidylcholine by rat lung during choline deficiency.

The effect of choline deficiency on the de novo pathway for phosphatidylcholine (PC) synthesis in the lung was investigated in rats fed a washed soy protein (lipotrophic) diet deficient in choline and methionine for 2-3 wk. Lungs from lipotrophic rats showed a decreased content of choline and choline-phosphate (P less than 0.05) compared with control but no change in content of cytidine 5'-diphosphocholine or PC. Isolated perfused lungs from lipotrophic rats were evaluated for choline and fatty acid utilization for PC synthesis. Lipotrophic lungs perfused with 5 microM [14C-methyl]-choline chloride showed increased incorporation into PC while there was no significant effect at saturating levels of choline (100 microM). There was increased incorporation of [1-14C]-palmitic acid into PC and diglyceride and increased incorporation of D-[U-14C]glucose into fatty acids of PC. Increased choline and glucose incorporation was not due to alteration of intracellular specific activity of these substrates. This study indicates the utilization of choline and fatty acid for PC synthesis is stimulated as a result of choline deficiency while lung CDP-choline concentration is maintained, possibly through regulation of choline phosphate cytidyl transferase activity. These mechanisms compensate for decreased choline availability to maintain the PC content of lungs.

Animals↗
PubMed1988

Oxygen-18 and deuterium labeling studies of choline oxidation by spinach and sugar beet.

Chenopods synthesize betaine by a two-step oxidation of choline: choline --> betaine aldehyde --> betaine. The pathway is chloroplastic; the first step has been shown in isolated spinach (Spinacia oleracea L.) chloroplasts to be O(2)- and light-dependent, the role of light being to provide reducing power (P Weigel, EA Weretilnyk, AD Hanson 1988 Plant Physiol 86: 54-60). Here, we report use of in vivo(18)O- and (2)H-labeling in conjunction with fast atom bombardment mass spectrometry to test for two hypothetical choline-oxidizing reactions that would explain the observed requirements for O(2) and reductant: a desaturase or an oxygenase. Simple syntheses for (2)H(3)-choline, (2)H(3), (18)O-choline, and (2)H(3), (18)O-betaine are given. A desaturase mechanism was sought by giving choline deuterated at the 2-carbon, or choline unlabeled at this position together with (2)H(2)O and by analyzing newly synthesized betaine. About 15% of the (2)H at C-2 was lost during oxidation of choline to betaine, and about 10% of the betaine made in the presence of 50% (2)H(2)O was monodeuterated. These small effects are more consistent with chemical exchange than with a desaturase, because 10 to 15% losses of (2)H from the C-2 position also occurred if choline was converted to betaine by a purified bacterial choline oxidase. To test for an oxygenase, the incorporation of (18)O from (18)O(2) into newly synthesized betaine was compared with that from (18)O-labeled choline, in light and darkness. Incorporation of (18)O from (18)O-choline was readily detectable and varied from about 15 to 50% of the theoretical maximum value; the (18)O losses were attributable to exchange of the intermediate betaine aldehyde with water. In darkness, incorporation of (18)O from (18)O(2) approached that from (18)O-choline, but in the light was severalfold lower, presumably due to isotopic dilution by photosynthetic (16)O(2). These data indicate that the chloroplast choline-oxidizing enzyme is an oxygenase.

Journal Article↗
PubMed1994

Restricting food intake does not exacerbate the effects of a choline-deficient diet on tissue carnitine concentrations in rats.

Previous reports in animals indicate that choline deficiency alters carnitine metabolism. Recent studies in humans suggest that choline deficiency occurs in individuals during long term total parenteral nutrition. Malnutrition is also a frequent complication in this population. We therefore examined the effect of restricting the intake of a choline-deficient diet on carnitine concentrations in plasma and tissues. Adult male rats were randomly assigned to one of four dietary regimens: control, choline deficient, restricted control (85% of control), or restricted choline deficient for 42-43 d. At the end of the experimental period, restricted animals weighed significantly less than their respective controls (P < 0.01). Liver weight relative to body weight and fat concentration were greater in choline-deficient animals (P < 0.01 and 0.001, respectively). Choline-deficient rats fed free access had elevated plasma carnitine concentration (P < 0.01). Urinary carnitine excretion was elevated in both groups of choline-deficient rats (P < 0.01), while liver, heart and muscle carnitine concentrations were lower than in controls (P < 0.05). Restricting dietary intake reduced plasma carnitine concentration in choline-deficient animals (P < 0.01), but did not alter tissue or urine carnitine concentrations in either group. Restricted, choline-deficient animals did not exhibit a worsening of the sequelae of choline deficiency. We conclude that choline deficiency alters carnitine concentrations in plasma and tissues and that restricting the intake of a choline-deficient diet does not alter this effect in tissues.

Animals↗
PubMed1981

Tissue choline studied using a simple chemical assay.

An enzymatic-radioisotopic assay was used to measure free choline in unextracted tissue. The lowest concentration of free choline in any tissue studied was present in human cerebrospinal fluid (mean, 5.7 microM; range, 1.8 + 31.2 microM). A postmortem increase in concentration of free choline occurred in blood (0.2 nmol/min.ml), kidney (13 nmol/min.g) and liver (22 nmol/min.g) of mice. The concentration of free choline in these tissues was estimated by extrapolation to be 5, 77, and 29 nmol/g (or ml), respectively. Several treatments were found to increase the concentration of free choline. For example, intraperitoneal administration of choline or 2-amino-2-methyl-propanol (a choline oxidase inhibitor) induced an increase in the level of choline i blood, kidneys, liver, and brain of mice, and administration of 2-dimethylaminoethanol (deanol) caused an increase in kidney and liver choline. The level of choline in blood was increased when rats were treated orally with either antibiotics or esters of choline such as phosphorylcholine, glycerylphosphorylcholine, laroylcholine, or propionylcholine. The results show that the concentration of free choline may be regulated by intestinal metabolism, availability of esterified precursors, and activity of enzymes that metabolize choline.

Adenosine Triphosphate↗