Orotic Acid (Vitamin B13)
Vitamin B13 is a compound from distillers consisting of dried solubles. It was later identified as orotic acid, an intermediate in pyrimidine metabolism. It is recognized as a treatment for MS (multiple sclerosis) and is dispensed under the name of "calcium orotate" (an essential growth factor in rats). Good sources are root vegetables and whey. Vitamin B13 is primarily used for metabolization of folic acid and vitamin B12.
Orotic acid is an intermediate in the metabolism of pyrimidines (nitrogenous heterocyclic compounds containing nitrogen atoms at positions 1 and 3; naturally occurring derivatives are components of nucleic acids: cytosine, thymidine, and uracil). It is used as a cosmetic ingredient, in medicine, as a feed supplement and in biochemical research. Orotic acid is a chemical overproduced in an alternative pathway when there is a block in the urea cycle. Excessive amounts of orotic acid are usually found in OTC (ornithine transcarbamylase) deficiency, citrullinemia, and oftentimes in argininosuccinic aciduria. Orotic acid determination is useful in delineating the cause of hyperammonemia.
Free orotic acid (OA) itself is known to get into cells by simply leaking (diffusing) through cell membranes, rather than by being actively transported. But diffusion is a relatively inefficient process, which limits the amount of OA that can enter a cell. By contrast, uracil-a compound almost identical to OA, only minus the carboxylic acid group--is taken up efficiently by a transporter protein that binds to uracil molecules and drags them into the cell. This transporter appears to be specific for uracil or similar molecules which are uncharged, but not for uracil’s close cousin OA (which is negatively charged at body pH).
Although orotic acid isn't officially considered a vitamin these days, over 40 years ago it was found to have growth-promoting, vitamin-like properties when added to the diets of laboratory animals. Subsequent nutritional studies in humans and animals revealed that OA has a "sparing" effect on vitamin B12, meaning that supplemental OA can partially compensate for B12 deficiency. OA also appears to have a direct effect on folate metabolism.
Many of the vitamin-like effects of OA are undoubtedly due to its role in RNA and DNA synthesis. (B12 and folate are also involved in DNA synthesis, but at a point downstream from where OA comes in.) Our bodies produce OA as an intermediate in the manufacture of the pyrimidine bases uracil, cytosine, and thymine. Together, these pyrimidines constitute half of the bases needed for RNA/DNA, the other half coming from the purine bases adenine and guanine which are synthesized independently of OA.
The enzyme orotate phosphoribosyltransferase (OPRTase), which is found in organisms ranging from yeast to humans, is responsible for catalyzing the first step in the conversion of orotic acid into uridine. It does so by facilitating the attachment of a ribose plus phosphate group to OA. The net result is the formation of a molecule named OMP (orotidine 5'-monophosphate), which in turn is the immediate precursor to UMP (uridine 5'-monophosphate).
Synonyms: 1,2,3,6-tetrahydro-2,6-dioxo-4-pyrimidinecarboxylic acid, uracil-6-carboxylic acid, 6-uracilcarboxylic acid, 6-carboxyuracil, 2,6-dihydroxy-4-pyrimidinecarboxylic acid, whey factor, animal galactose factor, oropur, orotyl, orodin, orotonin, oroturic
Molecular formula: C5H4N2O4
CAS No: 65-86-1