Molybdopterin synthesis

Llamas A, RR Mendel, G Schwarz (2004) Synthesis of adenylated molybdopterin. An essential step for molybdenum insertion. J Biol Chem 279 55241-55246. 

Pitterle, D. M., Johnson, J. L, and Rajagopalan, K. V. In vitro synthesis of molybdopterin from precursor Z using purified converting factor, J. 

K V. A sulfiirtransferase is required in the transfer of cysteine sulfur in the in vitro synthesis of molybdopterin from precursor Z in Escherichia coli, J Biol Chem 2001, 276, 22024-22031. 

Synthesis of metal-organic cofactors Molybdopterin-cofactor in dehydrogenases FeMo-cofactor for nitrogenase... 

X-ray crystallography, 40 20-21 synthetic models, 40 23-48 xanthane oxidase, 40 21-23 chalcogenide halides, 23 370-377, 413 Chevrel phases, 23 376-377 metal-metal bonding, 23 330, 373 structural data, 23 373-376 as superconductors, 23 376 synthesis, 23 371-372 chloride, 46 4-24, 35-44 heterocations of, 9 290, 291 cluster compounds, 44 45-46 octahedral, 44 47-49, 53-63 electronic structure, 44 55-63 molecular structure, 44 53-54 synthesis, 44 47-49 rhomboidal, 44 75-82 solid-state clusters and, 44 66-72, 74-75, 80-82, 85-87 tetrahedral, 44 72-75 triangular, 44 82-87 cofactor, 40 2, 4-12 anaerobic isolation, 40 5 molybdopterin and, 40 4-8 reduced form, 40 12 synthesis, 40 8-12 xanthine oxidase, 45 60-63 complexes... 

Aromatic compounds arise in several ways. The major mute utilized by autotrophic organisms for synthesis of the aromatic amino acids, quinones, and tocopherols is the shikimate pathway. As outlined here, it starts with the glycolysis intermediate phosphoenolpyruvate (PEP) and erythrose 4-phosphate, a metabolite from the pentose phosphate pathway. Phenylalanine, tyrosine, and tryptophan are not only used for protein synthesis but are converted into a broad range of hormones, chromophores, alkaloids, and structural materials. In plants phenylalanine is deaminated to cinnamate which yields hundreds of secondary products. In another pathway ribose 5-phosphate is converted to pyrimidine and purine nucleotides and also to flavins, folates, molybdopterin, and many other pterin derivatives. 

The Thil gene, which encodes aother sulfurtransferase protein, is also needed.3743 The enzymology of the insertion of this sulfur into the thiazole is uncertain but may resemble that involved in synthesis of biotin, lipoic acid, and molybdopterin.374 Linkage of the two parts of the thiamin molecule (step d, Fig. 25-21) is catalyzed by thiamin phosphate synthase, evidently via an SN2 type reaction.377-37713... 

Figure 18. Synthesis of a molybdenum dithiolene (via a [3 + 2] pathway) and its conversion to a thiophene derivative. Structure of urothione, the oxidative degradation product of a molybdopterin (228).

The pterins include the redox cofactors biopterin and molybdopterin, as well as various insect pigments. Folic acid is a conjugated pterin, in which the pteridine ring is linked to p-aminobenzoyl-poly-y-glutamate it is this linkage that renders folate a dietary essential, because it is the ability to condense p-aminobenzoate to a pteridine, rather than to synthesize the pteridine nucleus itself, which has been lost by higher animals. Biopterin (Section 10.4) and molybdopterin (Section 10.5) are coenzymes in mixed-function oxidases they are not vitamins, but can be synthesized in the body. Rare genetic defects of biopterin synthesis render it a dietary essential for affected individuals. 

In addition to the established vitamins, a number of organic compounds have clear metabolic functions they can be synthesized in the body, but it is possible that under some circumstances (as in premature infants and patients maintained on long-term total parenteral nutrition) endogenous synthesis may not be adequate to meet requirements. These compounds include biopterin (Section 10.4), carnitine (Section 14.1), choline (Section 14.2), creatine (Section 14.3), inositol (Section 14.4), molybdopterin (Section 10.5), taurine (Section 14.5), and ubiquinone (Section 14.6). 

Consistent with the dithiolene structure proposed for the oxidized derivative of molybdopterin (3), no nonexchangeable H resonances are observed in the region expected for the CH protons of a dithiolate structure (5b). The mass spectrum of 3 is also consistent with the proposed dithiolene structure (19, 34). Resonance Raman spectra of DMSO reductase show bands at 1575 cm (oxidized form) and 1568 cm (reduced form) that are assigned to the C=C stretch of the dithiolene unit of 2 (40). However, the delocalized electronic structure of dithiolene ligands makes it difficult to assign the C=C stretch with certainty. As Rajagopalan notes (19), ultimate proof of the structure [of molybdopterin] will have to await either X-ray studies on a molyb-doenzyme or unequivocal chemical synthesis of the molecule. ... 

The modeling and ultimate total synthesis of molybdopterin and Mo-co have been hampered by difficulties associated with the pterin chemistry involved. However, synthetic assaults on molybdopterin, the molybdenum cofactor, and the degradation products of the molybdenum cofactor are now well underway. The total chemical synthesis of urothi-one (7), the postulated metabolic excretory product of Mo-co (25), has recently been reported (4 7). Compound 7 is a naturally occurring substituted thiophene that is found in the urine of normal humans. It is absent (25) from the urine of children who lack the molybdenum cofactor due to a genetic defect and who are unable to metabolize sulfite (48). The absolute configuration of Form A (8), another degradation product of... 

Synthesis, characterization, and spectroscopy of model molybdopterin complexes... 

A similar coupling may be used to obtain pteridine 2 (R = C6H4C02-/-Bu).l5° This reaction has also been developed for the synthesis of the pteridinylalkynol 4, in racemic form, as a potential precursor to molybdopterin 5.219... 

Stable pyrano[2,3-g]pteridines related to molybdopterin have been synthesized <01CC123>. The synthesis of new heterocondensed pteridines has been reported <01JHC1173>. 

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