Orotic acid

Structural formula
General
Surname	Orotic acid
other names	1,2,3,6-tetrahydro-2,6-dioxopyrimidine-4-carboxylic acid; Uracil-6-carboxylic acid; Whey acid; 6-carboxy-2,4-dihydroxypyrimidine; Vitamin B 13 (out of date); OROTIC ACID ( INCI ) ;
Molecular formula	C 5 H 4 N 2 O 4
Brief description	colorless and odorless powder
External identifiers / databases
EC number	200-619-8
ECHA InfoCard	100,000,563
PubChem	967
ChemSpider	942
DrugBank	DB02262
Wikidata	Q425536
properties
Molar mass	156.1 g mol −1
Physical state	firmly
Melting point	348-350 ° C
pK s value	2.4; 8.13; 9.45;
solubility	heavy in water (1.82 g l −1 at 25 ° C); almost insoluble in ethanol ; soluble in aq. Alkalis;
safety instructions
GHS labeling of hazardous substances Caution
H and P phrases	H: 302-315-319-335
	P: 261-305 + 351 + 338
Toxicological data	2000 mg kg −1 ( LD 50 , mouse , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Orotic acid is a pyrimidine - derivative and intermediate in the biosynthesis of Uridinmonophosphats ( UMP ). Among other things, it occurs as a component of the nucleoside orotidine . The salts of orotic acid are called " orotates ".

history

Orotic acid was first isolated from cow whey in 1904 by the Italian researchers Biscaro and Belloni. They called the acidic substance orotic acid, derived from the Greek " orós ", whey . Since it was previously assumed that orotic acid was essential for life, it was also known as vitamin B ₁₃ .

Occurrence

Orotic acid is an intermediate metabolic product and occurs in yeasts and molds of the genus Neurospora such as Neurospora crassa , especially dairy products (including colostrum ) and numerous foods.

properties

Orotic acid is a white, odorless, sweet-tasting, crystalline powder that almost does not dissolve in water or ethanol . It is practically insoluble in organic solvents. The tri-base, medium-strength acid dissolves better in aqueous alkali lye. Colorless, prism-shaped crystals form during slow crystallization. In solid, crystalline form, orotic acid can be kept almost indefinitely.

presentation

It was first presented by the chemists Treat B. Johnson and Elmar F. Schröder in 1931. They were able to synthesize orotic acid by oxidation from 4-thiouracil-4-aldehyde or 4-uracilaldehyde on chromic acid.

Reactions

Orotic acid is an intermediate product in the biosynthesis of uridine monophosphate . Orotic acid is formed in organisms through the oxidation of dihydroorotic acid. This reaction is the fourth step in the pyrimidine de novo synthesis and is catalyzed by dihydroorotic acid dehydrogenase.

When a phosphoribosyl residue is transferred by the orotate phosphoribosyl transferase, orotic acid reacts in the subsequent step to form orotidine monophosphate (OMP), the decarboxylation of which leads to the formation of uridine monophosphate. This in turn is the starting product in the biosynthesis of the pyrimidine bases cytosine , thymidine and uracil .

Biological importance

If the urea cycle is disturbed , the accumulating carbamyl phosphate leads to an increased synthesis of orotic acid. Orotic acid accumulation in tissue and serum is also due to a hereditary deficiency in orotidine-5-phosphate pyrophosphorylase . The associated increased excretion in the urine is known as orotaciduria .

Although orotic acid is synthesized in smaller amounts in the body itself, it must be ingested through food to meet its daily needs.

Orotic acid has many functions in the organism.

Orotic acid can prevent the ATP level in the heart from being completely depleted. It is said to increase the amount of pyrimidine nucleotides in the liver, which then leads to an increased production of ATP in the myocardial area.

Furthermore, orotic acid and derivatives can improve memory and learning performance ( nootropic ). In animal experiments, improved adaptive performance such as improved formation of long-term memory could be demonstrated. The nootropic effect of absorbed orotic acid is attributed to the replenishment of the cerebral pyrimidine nucleotide pool, since the de novo synthesis of orotic acid in the brain is limiting for its availability.

Orotic acid is poorly absorbed through food (5–6%) because it is poorly soluble in water or lipids. The half-life in the blood is about 1 hour.

literature

J. Schmidt: Magnesium Orotate. In: Deutsche Apotheker Zeitung . 18, 1998, pp. 66-70.
Marcell Bachstez: About the constitution of orotic acid. In: Chemical Reports . Volume 63, Issue 4, 1930, pp. 1000-1007, doi : 10.1002 / cber.19300630437 .
Lubert Stryer: Biochemistry. Spectrum of Science Verlag, Heidelberg 1990, ISBN 3-89330-690-0 , pp. 633-634.
Eckhart Buddecke: Outline of Biochemistry. 8th edition. Walter de Gruyter, Berlin 1989, ISBN 3-11-012076-3 , p. 138.

Individual evidence

↑ Klaus Pietrzik, Ines Golly, Dieter Loew: Handbook Vitamins: for prophylaxis, advice and therapy . 1st edition. Elsevier, Urban & FischerVerlag, Munich 2008, ISBN 978-3-437-55361-5 , pp. 460-462 .
↑ Entry on OROTIC ACID in the CosIng database of the EU Commission, accessed on May 25, 2020.
↑ ^a ^b data sheet orotic acid (PDF) from Carl Roth , accessed on December 14, 2010.
↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j F. v. Bruchhausen, S. Ebel, AW Frahm, E. Hackenthal: Hagers Handbook of Pharmaceutical Practice. Volume 8: Substances E-O. Springer, ISBN 3-540-52688-9 , p. 1241.
↑ ^a ^b ^c Entry on orotic acid in the GESTIS substance database of the IFA , accessed on February 10, 2017(JavaScript required) .
↑ Orotic acid data sheet from Sigma-Aldrich , accessed on April 16, 2011 ( PDF ).

^ Treat B. Johnson and Elmer F. Schroeder: RESEARCHES ON PYRIMIDINES. CXXII. IMPROVED METHODS FOR THE SYNTHESIS OF OROTIC ACID . In: Journal of the American Chemical Society . tape 53 , no. 5 , May 1931, p. 1989–1994 , doi : 10.1021 / ja01356a057 .

↑ FL Rosenfeldt et al: Mechanism of cardioprotective effect of orotic acid. In: Cardiovascular Drugs and Therapy . 12, Suppl. 2, 1998, PMID 9794090 , pp. 159-170.

^ Science online lexica: Entry on orotic acid in the lexicon of neuroscience. Retrieved August 24, 2009.

[:0-1] Klaus Pietrzik, Ines Golly, Dieter Loew: Handbook Vitamins: for prophylaxis, advice and therapy . 1st edition. Elsevier, Urban & FischerVerlag, Munich 2008, ISBN 978-3-437-55361-5 , pp. 460-462 .

[CosIng-2] Entry on OROTIC ACID in the CosIng database of the EU Commission, accessed on May 25, 2020.

[roth-3] ta sheet orotic acid (PDF) from Carl Roth , accessed on December 14, 2010.

[hager-4] ↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j F. v. Bruchhausen, S. Ebel, AW Frahm, E. Hackenthal: Hagers Handbook of Pharmaceutical Practice. Volume 8: Substances E-O. Springer, ISBN 3-540-52688-9 , p. 1241.

[GESTIS-5] Entry on orotic acid in the GESTIS substance database of the IFA , accessed on February 10, 2017(JavaScript required) .

[Sigma-6] Orotic acid data sheet from Sigma-Aldrich , accessed on April 16, 2011 ( PDF ).

[7] Treat B. Johnson and Elmer F. Schroeder: RESEARCHES ON PYRIMIDINES. CXXII. IMPROVED METHODS FOR THE SYNTHESIS OF OROTIC ACID . In: Journal of the American Chemical Society . tape 53 , no. 5 , May 1931, p. 1989–1994 , doi : 10.1021 / ja01356a057 .

[Rosenfeldt-8] FL Rosenfeldt et al: Mechanism of cardioprotective effect of orotic acid. In: Cardiovascular Drugs and Therapy . 12, Suppl. 2, 1998, PMID 9794090 , pp. 159-170.

[9] Science online lexica: Entry on orotic acid in the lexicon of neuroscience. Retrieved August 24, 2009.