Orotic Acid What it is Although orotic acid was first discovered as a chemical material in whey in 1904 its biological importance was not appreciated until it was found to be a precursor of pyrimidines such as uridine triphosphate and cytidine triphosphate in many biological systems. Much of this research was undertaken in the 1940s and by the end of the 1950s it had been shown to promote the growth of micro-organisms such as Lactobacilli streptococci and Neurospora. It was also shown that, when combined with methionine, it stimulated the growth of young dairy calves and heifers and, when combined with lysine, it protected the livers of rats against hepatotoxic agents. It is found in milk and milk products and in products containing micro-organisms such as yeasts. Soil and crops grown in the soil may also contain orotic acid, orotidine or orotate salts. It has been variously called the whey factor, the animal galactose factor and vitamin B13. Chemically, it is classified as uracil-4-carboxylic acid. Both the methyl and ethyl esters appear to have similar beneficial effects to the acid. Other compounds such as orotidine, an orotic acid glycoside, have been obtained from various cultures of micro-organisms. Salts such as calcium, zinc or magnesium orotate show similar activity. What it does At least three enzymes in the pyrimidine synthetic pathway contain orotic acid or orotidine. These occur principally in mammary tissue. Pyrimidines may also derive directly from orotic acid and thus orotic acid increases the rate and capacity of various metabolic pathways where pyrimidine components are operating. In particular, growth rate may be encouraged by enhanced supplies. Research results suggest that microbial growth or efficiency is stimulated by orotic acid. It seems to follow that any biosynthetic process in higher animals can also be assisted by orotic acid. Volatile fatty acid production is a bacterial function and appears to be stimulated by orotic acid. Orotic acid and vitamin B12 have similar effects on the metabolism of the single-carbon moiety whereby orotic acid increases the concentration of folate derivatives and influences the enzymes involved in the synthesis and utilisation of folate intermediates. Orotic acid also results in an increase in liver RNA, presumably because it increases messenger RNA synthesis. It has been used in human medicine where it appears to inhibit or reduce hepatic cholesterol biosynthesis. If insufficient is available No conditions related to insufficient supplies of orotic acid have been defined. In theory, a reduced supply would lead to lower bacterial activity. The biosynthesis of microbial protein and B-group vitamins in the caecum could be affected. The main source of supply is milk so milk-fed foals should not be deficient. Some of the non-milk substitute powders may not contain orotic acid and foal growth under such a feed regime might be restricted. It seems possible that horses kept intensively in clean conditions might show reduced performance or even stunting if the feed contained no milk products or supplementary orotate. Such conditions might be accompanied by apparent vitamin deficiency problems (folate, vitamin B12, vitamin C, thiamine, etc.) and by poor digestion and absorption. However this seems very unlikely and has never been shown in horses or other animals kept under normal practical farming conditions. If too much is given Work with rats and human patients suggests that grossly excessive supplies of orotic acid can induce fatty liver conditions and inhibit hepatic biosynthesis. However this hypervitaminosis problem has not been reproducible with horses or with experimental animals. How it is measured Orotic acid can be separated from milk by dialysis followed by column chromatography and determination by gas-liquid chromatography. A simpler method by converting it to barbituric acid and then measuring its colour reaction with p-dimethylaminobenzaldehyde in n-propanol has been used successfully. Assessment of status Nothing is known of the orotic acid status of horses. Biosynthesis The main organ of manufacture appears to be mammary tissue. One of the main precursors is aspartic acid. An intramammary infusion of carbon-14-labelled aspartic acid indicates that the orotic acid in milk originates almost exclusively in mammary cells. Only very small traces of orotic acid have been found in other organs such as the liver. As far as is known orotic acid is not produced by plants or by bacteria. Relationships with other ingredients Orotic acid seems most effective when combined with an amino acid. Combinations with methionine and lysine have been shown to be particularly helpful. Orotic acid has a close metabolic relationship with vitamin B12 and folic acid. Since it controls the metabolic pathways which include folate-splitting enzymes a shortfall of orotic acid can induce an apparent deficiency of folic acid. Requirements and allowances Since orotic acid has not been confirmed as an essential dietary component, no requirement has been established for horses. When it has been used in growth rate experiments graded amounts have not been used so it is difficult to recommend suitable quantities where it has been decided to supply orotic acid. In the absence of any other information it is suggested that a daily allowance of 1 mg for each kg liveweight could be useful if situations develop where it might be beneficial. Diets for very young foals reared away from the mare should be supplemented with 400 mg orotic acid per kg if no milk or milk products are included. Contents of feed ingredients Most of the research on orotic acid has been involved in determining the amounts present in milk. Some of the earlier assays may not have separated all the pyrimidines from orotic acid, leading to inflated values. Milk from mares contains 0-2 mg/litre.