Choline orotate

S51 Schambeck, H., Schaffner, F., Keppler, D. and Decker, D. Ultrastructural studies on the effect of choline orotate on galactosamine induced hepatic injury in rats. Exp. Mol. Pathol., 16, 33-46 (1972)... 

Orotic acid in the diet (usually at a concentration of 1 per cent) can induce a deficiency of adenine and pyridine nucleotides in rat liver (but not in mouse or chick liver). The consequence is to inhibit secretion of lipoprotein into the blood, followed by the depression of plasma lipids, then in the accumulation of triglycerides and cholesterol in the liver (fatty liver) [141 — 161], This effect is not prevented by folic acid, vitamin B12, choline, methionine or inositol [141, 144], but can be prevented or rapidly reversed by the addition of a small amount of adenine to the diets [146, 147, 149, 152, 162]. The action of orotic acid can also be inhibited by calcium lactate in combination with lactose [163]. It was originally believed that the adenine deficiency produced by orotic acid was caused by an inhibition of the reaction of PRPP with glutamine in the de novo purine synthesis, since large amounts of PRPP are utilized for the conversion of orotic acid to uridine-5 -phosphate. However, incorporation studies of glycine-1- C in livers of orotic acid-fed rats revealed that the inhibition is caused rather by a depletion of the PRPP available for reaction with glutamine than by an effect on the condensation itself [160]. 

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]. 

Fujio, T., and A. Maruyama. 1997. Enzymatic production of pyrimidine nucleotides using Corynebacterium ammoniagenes cells and recombinant Escherichia coli cells enzymatic production of CDP-choline from orotic acid and choline chloride (part I). Biosci. Biotechnol. Biochem. 61 956-959. 

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)... 

Simon, J. B., Scheig, R. and Jvlatskin, G. Protection by orotic acid against the renal necrosis and fatty liver of choline deficiency. Proc. Soc. Exp. Biol. Med., 129,874-877... 

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