Choline deficiency, effects

Yoshiji, H., Nakae, D., Mizumoto, Y., Horiguchi, K., Tamura, K., Denda, A., Tsujii, T. and Konishi, Y. (1992). Inhibitory effect of dietary iron deficiency on inductions of putative preneoplastic lesions as well as 8-hydroxydeoxyguanosine in DNA and lipid peroxidation in the livers of rats caused by exposure to a choline-deficient L-amino acid defined diet. Carcinogenesis 13, 1227-1233. 

Orotic acid added to rat diet also provokes an. excessive biosynthesis of porphyrins in liver, erythrocytes and bone marrow. Administration of adenine monophosphate (AMP) counteracted this effect of orotic acid intoxication [165]. Haemorrhagic renal necrosis in rats, caused by choline deficiency, can be relieved by orotic acid [166], Simultaneous supplementation of the diet with adenine does not influence the protective effect of orotic acid. It has been suggested that orotic acid may lower the body requirement for choline through a metabolic interaction—orotic acid may stimulate the cytidine phosphate choline pathway of lecthin biosynthesis [166]. 

Pomfret, E.A., daCosta, K.A. Zeisel, S.H. (1990) Effects of choline deficiency and methotrexate treatment upon rat liver. J. Nutr. Biochem., 1, 533-541... 

Some of the unusual features of folic acid noled by investigators include (I) folic acid antagonists used in cancer therapy with temporary remissions (2) lolic acid occurs in chromosomes (3) folic acid is distributed throughout cells (4) needed for mitotic step metaphase to anaphase (5) antibody formation decreased in lolic acid deficiency (6) choline-sparing effects (7) analgesic in humans—pain threshold is increased (8) antisulfonatnide effects (9) enterohepatic circulation of folate (10) synthesized by psittacosis virus (11) concentrated in spinal fluid. 

A choline deficient (CD) diet has been shown to exert a strong promoting effect on the emergence of foci of enzyme altered hepatocytes and on the induction of hepatomas in rats initiated with a carcinogen. 

We have been investigating a few selected aspects of the mechanism of liver tumor promotion by a diet devoid of choline, a choline deficient (CD) diet. The diet is an effective promoter of the emergence of early presumptive preneoplastic foci of Y-glutamyltranspeptidase (GGT)-positive hepatocytes as well as of the progression of GGT-positive foci to hepatomas (3 4). A CD diet with a high fat content (14%) exerted a stronger promoting action than a CD diet with a low fat content (5%) (5). 

DEHP effects on the peroxisomal system of the liver appeared to be increased in rats kept on a choline deficient diet (Perera et al. 1986). This conclusion was based on an increase in the conjugated dienes in the microsomes of choline-deficient animals exposed to 500 mg/kg DEHP for 4 weeks. Conjugated dienes are indicators of free radical oxygen modification of cellular lipids. 

The effects of choline deficiency can be demonstrated easily using animals. One of the earliest is a fatty liver. Feeding rats a choline-free diet for 1 day doubles the fat (triglyceride) content of their livers. Rats that survive the continued consumption of such diets can accumulate over 50 times the normal level of hepatic fat. This condition results from impairment of the normal secretion of fatthin shell of phospholipid and protein. 

Tyombardi, B. (19711, Effects of choline deficiency on rat hepatocyte. Fed. Proc. 30,139-142. 

Severe deficiency of dietary protein produces a marked lowering of plasma albumin, and this is usually considered to occur as a result of depressed synthesis due to the deprivation of essential amino acids. A marked hypoalbuminemia in the rat and dog (F7) and in the cat (G24) has resulted from experimentally induced chronic choline deficiency. The effect was not reversed by a dietary supplement of methionine, but was reversed by choline supplementation. This situation bore no direct relation to the fatty... 

From 1952 to 1962, several experimental studies using rats fed a choline-deficient diet reported the development of aortic arteriosclerosis.171-173 Using rats fed a choline-deficient diet, Sidransky et al.174 reported that elevated (2%) dietary tryptophan affected the elevated serum lipid levels of rats fed the choline-deficient diet for 1 week. Within 1 week the added dietary tryptophan to the choline-deficient diet caused a return in serum cholesterol, HDL cholesterol, and triglyceride values to levels present in rats fed the choline-supplemented diet. The significance of the alterations in serum lipids due to added dietary tryptophan was unknown, but it stressed that a specific amino acid (L-tryptophan) excess created a further nutritional imbalance, which could influence the altered circulating serum lipids due to choline deficiency. The alterations in serum lipid due to choline deficiency were thought to influence the development of arteriosclerosis in the rat, and possibly the added dietary tryptophan was able to prevent the effect. Further experimental studies are needed to determine whether this speculation was valid. 

Wilgram, G. F., Best, C. H., and Blumenstein, J., Aggravating effect of cholesterol on cardiovascular changes in choline-deficient rats, Proc. Soc. Exp. Biol. Med., 89, 476, 1955. 

Filipowicz, C. M. and McCauley, R. B., The effect of choline deficiency on the outer membranes of rat liver mitochondria, Biochim. Biophys. Acta, 734, 373,1983. 

The fatty infiltration of the liver which accompanies the ingestion of orotic acid does not seem to be accompanied by serious pathological disturbances [293] and is readily reversible, unlike the development of fatty liver induced by a choline deficient diet. Supplementation of the orotic acid diet with adenine essentially modifies the effect of orotic acid [294]. Since PRPP is required for both the synthesis of purines and the metabolism of orotic acid, the decrease in the pool of adenine nucleotides is caused [295,296] by an inhibition of purine synthesis de novo due to extensive depletion of PRPP during the conversion of orotic acid to UMP. After the disappearance of orotic acid from the liver of animals previously fed a diet containing orotic acid, stimulation of the synthesis of adenine nucleotides occurred. 

M42 Monserrat, A. J., Porta, E. A. and Hartcroft, W. St. Orotic acid effects on the kidney. Changes in choline-deficient weanling rats. Arch. Pathol., 87, 154-163 (1969)... 

Studies in experimental species demonstrate that methyl donor availability affects the methylation of iAs. In mice exposed to arsenite (As ), depletion of the intracellular pool of 5-adomet by treatment with periodate-oxidized adenosine (PAD), an inhibitor of 5-adomet synthesis (Hoffman 1980), results in reduced urinary excretion of DMA (Marafante and Vahter 1984). Marafante and Vahter (1986) showed that consumption of choline-deficient diet decreased the urinary excretion of DMA and increased tissue As retention in rabbits given 0.4mg arsenate (As )/kg i.v. The same effect of a diet deficient in choline, methionine, and protein was observed in rabbits after administration of 0.4mg As Vkg i.v. (Vahter and Marafante 1987). 

In addition to this effect choline seems to have an accelerating effect on fatty acid oxidation (Artom 1958). The mechanism of this action is unknown, nor is it clear whether the quantitative effect on fatty acid oxidation could explain the accumulation of fat in the liver of choline deficient animals. 

Fatty livers are also formed, in the presence of adequate choline, by diets deficient in amino acids other than methionine. This has been shown for threonine (SiNGAL et al. 1954) lysine and tryptophan (Vennart et al. 1958). Threonine deficiency, like choline deficiency, also leads to an increased synthesis of fatty acid from acetate (Yoshida and Harper 1960). An increase in synthesis has also been observed when cystine is added to a low protein diet. The relative importance of these effects for the formation of fatty livers is still uncertain. 

Wissler et al. (1954) and Moskowitz et al. (1956) produced atheromatous lesions in middle-aged obese male rats with a diet with an average composition similar to actual diets of certain patients. This diet was not choline deficient, but contained lard to an appreciable amount however, the choline seemed to have an aggravating effect on the lesions. The difference in results in this and the foregoing experiments cannot yet be explained. It certainly points to the important role of imbalance in the dietary composition, and the possible odd effects of relative deficiencies. A similar observation was made by Jones et al. (1957) with methionine, which gave a hypercholesterolemia but was without effect on the number of lesions. Methionine given together with vitamin E, however, reduced the cholesterol levels to those of the normal controls, while vitamin E alone did not have this effect. 

As an illustration of the effects of a cold environment the results of Sellers and You (1956) will be mentioned. Rats on a choline-deficient diet had fewer cardiovascular lesions if kept in the cold (1-3 C.) than did a control group living at a normal room temperature, whereas for the choline-supplemented groups the reverse was true. In this connection Client (1950) found an increase of the iodine number of the body fat in rats on exposure to a temperature of 10° instead of 20° C. This might be due to oleic acid, which can be produced in the body, rather than necessarily to the essential polyunsaturated fatty acids. 

EFFECTS OF DIETARY FOLATE, VITAMIN AND METHIONINE/CHOLINE DEFICIENCY ON IMMUNE FUNCTION... 

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