Ribose-5-phosphate, formation

This pathway is variously known as the pentose phosphate, hexose monophosphate or phosphogluconate pathway, cycle or shunt. Although the pentose phosphate pathway achieves oxidation of glucose, this is not its function, as indicated by the distribution of the pathway in different tissues. Only one of the carbons is released as CO2, the key products are NADPH and ribose 5-phosphate, both of which are important for nucleotide phosphate formation and hence for synthesis of nucleic acids (Chapter 20). The... 

The routes involved in the formation of the various furan sulphides and disulphides involve the interaction of hydrogen sulphide with dicarbonyls, furanones and furfurals. Possible pathways are shown in Scheme 12.8. Furanthiols have been found in heated model systems containing hydrogen sulphide or cysteine with pentoses [56-58]. 2-Methyl-3-furanthiol has also been found as a major product in the reaction of 4-hydroxy-5-methyl-3(2H)-furanone with hydrogen sulphide or cysteine [21, 59]. This furanone is formed in the Maillard reaction of pentoses alternatively it has been suggested that it may be produced by the dephosphorylation and dehydration of ribose phosphate, and that this may be a route to its formation in cooked meat [21, 60]. 

The two intermediates in the conversion of anthranilate to indole-3-glycerol phosphate, phosphoribosylan-thranilate and l -(O-carboxyphenylamino)-1 -deoxyribu-lose-5 phosphate, were originally postulated to account for the involvement of phosphoribosyl pyrophosphate in indole-3-glycerol phosphate formation. Support for the postulate was obtained when the dephosphorylated derivative of the second of these intermediates was found in the culture fluids of certain tryptophan-requiring bacterial mutants. The corresponding derivative of the first intermediate has not been found, probably because of its instability. Indeed, this compound, when formed in extracts, is rapidly broken down to anthranilate and ribose-5-phosphate. 

Hodge et al. (45) discussed mechanisms for formation of methyl furanones and related substances from Amadori compounds. They have been produced by heating D-ribose and D-ribose phosphate with ammonia (46 47). Hicks and Feather (48) demonstrated that the Amadori compound 1-benzylamino-l-deoxy-D-threo-pentulose dehydrates to 4-hy-droxy-5-methyl-3(2H)-furanone and it has also been identified as a degradation product of L-ascorbic acid. This compound is believed to be formed from ribose-5-phosphate, and gained prominence when it was isolated from beef by Tonsbeck et al. (49). It became more apparent as a precursor of meat flavor when Van den Ouweland and Peer (50) reacted it and its thio analog with HaS to produce a number of sulfur compounds, some of which had meaty odors. 

In 1932 Levene and Harris128 showed that the hydrolysis of xanthylic acid gave rise to the formation of a D-ribose phosphate which was not identical with the known D-ribose 5-phosphate. Since xanthylic acid is the monophosphate derivative of a ribofuranoside of xanthine it followed that the new phosphate was either D-ribose 2-phosphate or the 3-isomer (L). Shortly thereafter the same authors129 succeeded in reducing the new D-ribose phosphate with hydrogen in the presence of platinum oxide to a ribitol phosphoric acid (LI) which was completely... 

Purine nucleotides can be synthesized in the organism from relatively simple building blocks ribose, phosphate, glycine, formate, aspartate, glutamine, and C02. The origin of each purine base component is summarized in Figure 10.5,... 

The pyrimidine ring is assembled first and then linked to ribose phosphate to form a pyrimidine nucleotide. PRPP is the donor of the ribose phosphate moiety. The synthesis of the pyrimidine ring starts with the formation of carbamoylaspartate from carbamoyl phosphate and aspartate, a reaction catalyzed by aspartate transcarbamoylase. Dehydration, cyclization, and oxidation yield orotate, which reacts with PRPP to give orotidylate. Decarboxylation of this pyrimidine nucleotide yields UMP. CTP is then formed by the amination of UTP. 

The purine ring is assembled from a variety of precursors glutamine, glycine, aspartate, N formyltetrahydrofolate, and (XT. The committed step in the de novo synthesis of purine nucleotides is the formation of 5-phosphoribosyIamine from PRPP and glutamine. The purine ring is assembled on ribose phosphate, in contrast with the de novo synthesis of pyrimidine nucleotides. The addition of glycine,... 

The pentose-phosphate pathway. The early steps of the pentose-phosphate pathway are shown in detail as for a pentose-phosphate formation. This pathway produces two NADPHs and ribose-5-phosphate. The reformation of hexose phosphate involves C3,... 

Both ribose phosphate and an AMP moiety must be added to nicotinamide in order to convert it to NAD-I-. The ribose phosphate is derived from PRPP when a phosphoribosyl transferase catalyzes the formation of nicotinamide ribonucleotide or nicotinamide mononucleotide. The final step utilizes ATP, which serves as an adenyl donor for the formation of the dinucleotide NAD-l-. 

The pathways by which ribose phosphates are formed will be considered in two stages the initial formation of pentose phosphates in general, and the formation of PP-ribose-P and ribose-l-P. 

The formation of PP-ribose-P is catalyzed by the enzyme, ribose phosphate pyrophosphokinase ... 

The above-mentioned studies of Krebs had shown that hypoxanthine was closer to the purine biosynthetic pathway than was uric acid. In 1951 Greenberg (8) isolated radioactive inosinate, as well as radioactive hypoxanthine, following incubation of C-formate in a cell-free system with all of the other necessary precursors (Fig. 7-1). The specific activity of inosinate was higher than that of hypoxanthine during short incubations and approached that of the precursor formate. This work identified the end product as inosinate rather than hypoxanthine, adenylate, or other purine derivative, and thereby showed that ribose phosphate had been added at some point prior to the completion of the biosynthetic pathway. 

It was not until 1953 that Goldwasser (9) and Williams and Buchanan (10) showed that purine bases could be converted to ribonucleotides by a one-step process, without the intermediate formation of ribonucleosides. The source of the ribose phosphate moiety was discovered in 1955 to be PP-ribose-P in the course of studies of adenylate synthesis by Kornberg et al. 11), and of inosinate synthesis by Korn et al. 12) extracts of yeast, beef liver, and pigeon liver were employed. The enzymes involved were at first called nucleotide pyrophosphorylases, but are now known as purine phosphoribosyltransferases. The general reaction is... 

Since ribose phosphate compounds are involved at some stage in purine synthesis, knowledge of the mechanism of ribotide formation has become a fundamental aspect of the purine problem. The exact enzymatic step mediating the coupling of ribose phosphate to a purine precursor is not known, although the addition is thought to occur before the AIC skeleton is completed (in view of the negative bank experiments discussed above). Since AIC and hypoxanthine are both converted to their respe< -tive ribotides, it was hoped that a study of hypoxanthine conversion to inosinic acid would reveal some of the important aspects of the fundamental reactions of ribotide synthesis. 

Since orotic acid was utilized for pyrimidine formation, in contradistinction to free pyrimidine bases, it is evident that it or a closely related compound must have been coupled to a ribose or ribose phosphate... 

AsHWELL, G. and Hickman, J. (1954) Formation of xylulose phosphate from ribose phosphate in spleen. J. Am. Chem. Soc. 76, 5589. 

Recent studies on xylose metabolism in cell-free extracts of Laclobaeillua pentosus tend to confirm this mechanism, at least until the stage of phosphorylation of xylulose. The accumulated pentose phosphate, however, included 70 to 80% of ribose phosphate and a ketose fraction rich in ribulose-5-phosphate. n-xylulose-5-phosphate was not detected but may have been a transitory intermediate. The mechanism of formation of compounds of the ribose series from xylose is not clear at present. (Lampen, J. 0., J. Biol. Chem. 204, 999 (1953).)... 

Intramolecular photocycloaddition is also reported to occur in the thiothymidine thymidinyl phosphates (80, R = H) and this gives the thietane (81) and the ring-opened thiol (82) (Scheme lO). The importance of this process is related to lesion in DNA. Irradiation of (80, R = Me) gives a new type of photoproduct (83) in the nucleic acid series that involves attack of the thiocarbonyl across the propene moiety of the thymidine ring. Irradiation at 366 nm in aqueous solution of the thiothymine (84) in the presence of adenine derivative (85) results in the formation of the adduct (86) this is formed presumably by way of the (2-l-2)-cycloaddition reaction between the C=S and the C=N bonds. Inter-molecular (2-i-2)-cycloaddition is also reported in the photoreaction of (84) with pyrimidinone derivative. Intramolecular photocycloaddition also occurs between thymine and 6-thioinosine derivatives tethered with ribose-phosphate-ribose and thietanes are obtained. ... 

Irradiation of thiouracil tethered by peptide or ribose-phosphate (144) at 366 nm in water results in the formation of the products (145, 146) (Scheme 20). °... 

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