Camillo Artom

LECITHIN FORMATION BY METHYLATION OF INTACT PHOSPHATIDYL DIMETHYLETHANOLAMINE

S>Results are reported from tracer studies of lecithin formation by methylation of intact phosphatidyl dimethylethanolamine (DME). After incubation of C/sup 14/ labeled DME with rat liver slices, the isotope was found to be present in the DME as well as in the choline moiety of the phospholipids. Results are tabulated from typical experiments. Possible reaction mechanisms involved are discussed. (C.H.)

The Relative Toxicity of l- and dl-Serine in Rats.

Summary A comparison has been made of the relative toxicity of l- and dl-serine in rats. Under the same experimental conditions, the administration of the natural l isomer was not accompanied by the clinical and pathological alterations and by the chemical changes in the urine, characteristically found in animals receiving the racemie mixture. It appears, therefore, that the unnatural d-isomer is chiefly responsible for the injurious action of dl-serine.

Methylation of phosphatidyl monomethylethanolanine in liver preparations

Abstract Recent reports have indicated that lecithin (“phosphatidyl choline”) can be formed by stepwise methylation of the nitrogenous moieties of intact phospholipids ( Bremer et al., 1960 ; Artom 1960; Gibson et al., 1961 ). With liver microsomes, the additions of non-labeled synthetic DME-, or MME-containing phospholipids (but not that of phosphatidyl EA) stimulated the incorporation of C 14 from Me-methyl-C 14 into lecithin ( Bremer and Greenberg, 1961 ; Cooksey and Greenberg, 1961 ). Attempts to demonstrate more directly a methylation of C 14 -labeled phosphatidyl EA by liver homogenate, or by its fractions, were not successful ( Artom, 1962 ). On the other hand, such preparations actively converted labeled phosphatidyl DME into lecithin ( Artom and Lofland, 1960 ; Artom, 1962 ). Similar evidence for the methylation of intact phosphatidyl MME is presented in this communication.

Lipide synthesis in aorta preparations from atherosclerosis-susceptible or resistant pigeons

Abstract Certain breeds of pigeons exhibit a very high incidence of aortic lesions which closely resemble those of human atherosclerosis. The aortas of other breeds almost never show lesions. When minced aortas of atherosclerosis-susceptible, or, respectively, resistant breeds were incubated with acetate-1-C14, no significant differences between the two breeds were apparent in the amounts of C14 incorporated into the digitonin-precipitable substances. Of the C14 in the latter fraction, only a portion was actually incorporated into cholesterol. In atherosclerosis-susceptible pigeons lesions are found only, or predominantly, in the distal half of the thoracic aorta. In both susceptible and nonsusceptible breeds of pigeons this portion of the aorta is much more active for the incorporation of C14 into the lipides than is the proximal portion.

Enzymes for the formation of lecithins by transmethylation in the livers of developing rats.

Summary The activities of enzymes involved in the transmethylating pathway for the formation of lecithins (phosphatidyl choline) were determined in homogenates of the livers of rats at various stages of development. If the values are expressed per unit of protein weight, the enzyme synthesizing adenosylmethionine appears to be quite active at the end of the second week of fetal life. In contrast, values for the phospholipid methyltransferase, the enzyme catalyzing the stepwise methylation of a phospholipid (presumably phosphatidyl ethanolamine) to lecithin, remain quite low in the fetal livers, increase rapidly after birth, and reach their peak at about the eighth day of extrauterine life. This pattern is similar to that previously observed for choline phosphotransferase, the enzyme which catalyzes the final step in the cytidine-dependent pathway, except that the latter enzyme increases more markedly during the last week of fetal life, suggesting that this pathway reaches full development somewhat earlier than the transmethylating pathway.

Subacute Toxicity of Radioactive Phosphorus as Related to the Composition of the Diet

Summary In mice on a 10% casein, 32% fat diet, the LD50 dose at the 21st day lies between 4 and 6 microcuries per g of body weight. Neither the fatty infiltration of the liver (induced by a deficiency of lipotropic factors, with or without partial poisoning with OCl4), or its prevention (by supplementing the diet with choline) changes the survival figures. The time of 50% deaths, the percentage of survivors at the 21st day and the average survival time of mice injected with P32 are highest with a diet low in fat and in protein, and are significantly decreased when the level of the fat, or of the protein, or both, are increased in the diet. Enrichment of the diets with inorganic phosphate seems to afford a moderate, but significant degree of protection against the injurious action of P32.

Effects of pantothenic acid and its analogs in radiation injury by P32.

Summary A significant protection against the injurious effects of P32 was observed by the administration of pantothenic acid to mice on a deficient diet. Pantoyltaurine was almost as effective in this respect as the natural vitamin.ω-methyl pantothenate was totally ineffective.

A protective role of pyridoxin against the toxic effects of P32.

Summary Mice placed on pyridoxin-free diets were injected with a single dose of radioactive phosphate (5-6 μc/g). In the animals maintained on a low protein diet (in which symptoms of vitamin deficiency did not appear), the administration of pyridoxin did not affect the survival. On the contrary a marked protection by pyridoxin against the injurious effects of P32 was observed in experiments in which the vitamin deficiency had been made more severe by adding a pyridoxin analog (desoxypyridoxin) to the low protein diet, or by increasing the requirements for the vitamin (high protein diets with added cystine or methionine). In these experiments the differences between the groups receiving and those not receiving pyridoxin were larger than the differences which might result from a simple additive effect of the internal radiation and vitamin deficiency.

Some Dietary Factors Which Reduce the Toxicity of dl-Serine in Rats.

Summary The administration of ample amounts of pure B vitamins to rats on an experimental diet, receiving dl-serine by stomach tube, reduces considerably the mortality and the severity of the clinical symptoms. Of the B vitamins tested, pyridoxine was most effective.

Variations of some constituents in the urine of rats receiving dl-serine and dl-alanine.

Summary The variations of some chemical constituents in the urine of rats receiving dl-serine have been studied quantitatively. The results have been compared with those of similar experiments in which dl-alanine has been given. In the serine groups, a significant proportion of the administered amino acid is excreted in the urine. In addition, in the first few days of serine administration, the urine contained protein and sugar, and the amounts of bisulfite-binding and of reducing substances were elevated. The presence of ethanolamine in later periods of the experiment appears probable. None of these changes was observed in the urine of animals receiving dl-alanine. The possible bearing of these results to the injurious action of serine is discussed. At any rate, the present data confirm and extend the indication of chemical changes in the urine which are as typical as the other clinical and pathological alterations found in rats receiving dl-serine.