Prebiotic synthesis of orotic acid parallel to the biosynthetic pathway

Abstract

By heating an aqueous solution of aspartic acid and urea, carbamylaspartic acid is first formed and then the molecule is cyclized to dihydroorotic acid (DHO) with loss of water. Irradiation of an aqueous solution of DHO with a tungsten lamp yields orotic acid by photo-dehydrogenation of the molecule. This pathway of orotic acid formation is quite similar to that of biosynthesis of the molecule.

Which Way to Life?

“…Only the amino imidazole carboxamide ribotide in the biosynthetic pathway is similar to the amino imidazole carbonitrile synthesized in the prebiotic pathways. Additional examples include (a) the decarboxylation of orotic acid which yields uracil (Ferris and Joshi 1979); (b) the chemical synthesis of glutamic acid from α-ketoglutarate, ammonia and reducing agents (Morowitz et al 1995); (c) pyrrole synthesis from UV-irradiated δ-aminolevulinic acid (Szutka 1966); (d) pyrimidine synthesis from dihydroorotic acid (Yamagata et al 1990); and (e) the production of acetic acid from the hydrolysis of the activated thioester CH 3 -CO-SCH 3 formed from the NiS/FeS-mediated reaction of CO and CH 3 SH (Huber and Wächtershäuser 1997). The similarities between these reactions and their enzyme-mediated counterparts do not necessarily indicate an evolutionary continuity between prebiotic chemistry and biochemical pathways, but may reflect chemical determinism.…”

On the Origin of Metabolic Pathways

“…If this were the case, then it would be relatively simple to trace the origin of a metabolic pathway. A number of attempts have been made to retrace the steps, including pyrrole synthesis using ␦-aminolevulinic acid as precursor (Szutka 1966), pyrimidine synthesis from dihydroorotic acid (Yamagata et al 1990), and purine synthesis from HCN (Oro 1960), but these comparisons are rather forced.…”

“…Since homoserine and aspartic acid are prebiotic compounds, they could be mobilized according to the Horowitz hypothesis to yield methionine and threonine after the latter were exhausted from the environment. An additional example would be the photochemical decarboxylation of orotic acid to uracil (Ferris and Joshi 1979;Yamagata et al 1990), but the orotic pathway to pyrimidines seems to be a minor prebiotic route.…”

Complexity, self-organization and the origin of life: The happy liaison?

“…Only the amino imidazole carboxamide ribotide in the biosynthetic pathway is similar to the amino imidazole carbonitrile synthesized in the prebiotic pathways. In addition to the the decarboxylation of orotic acid which yields uracil (Ferris & Joshi, 1979) discussed above, other examples include (a) the chemical synthesis of glutamic acid from a-ketoglutarate, ammonia and reducing agents (Morowitz et al 1995); (b) pyrrole synthesis using from UV-irradiated d-aminolevulinic acid (Szutka, 1966); (c) pyrimidine synthesis from dihydroorotic acid (Yamagata et al 1990); and (d) the production of acetic acid from the hydrolysis of the activated thioester CH3-CO-SCH3 formed from the NiS/FeS-mediated reaction of CO and CH3SH (Huber & Wächsterhäuser, 1997). The similarities between these reactions and their enzyme-mediated counterparts may reflect chemical determinism, and not necessarily indicate an evolutionary continuity between prebiotic chemistry and biochemical pathways.…”

“…This is the case of the alkaline degradation of glucose 6-phosphate (Degami & Halmann, 1967) and the clay-mediated deamination of adenine into hypoxanthine (Strasak. & Sersen, 1991), as well as the prebiotic synthesis of (a) 4-amino imidazole 5-carboxamide (a key intermediate in abiotic formation of guanine and hypoxanthine) which results from the hydrolysis of 4-amino imidazole 5-carbonitrile or the corresponding carboxamidine, and which is an intermediate, as a riboside, in the biosynthesis of purines (Oró & Kimball, 1962); (b) the photo-dehydrogenation of dihydroorotate, which yields orotic acid in a reaction comparable to the NAD-dependent dehydroorotate dehydrogenase-mediated step in pyrimidine biosynthesis (Yamagata et al 1990; uracil formation via the nonenzymatic photochemical decarboxylation of orotic acid (Ferris & Joshi, 1979). These similarities, however, do not necessarily indicate an evolutionary continuity between prebiotic chemistry and biochemical pathways, but may reflect of chemical determinism.…”