Ribose metabolic source

Few of these have been found so far, the first not until 1944, in a poisonous South African plant, Gifblaar . The toxic principle of this was identified44 as fluoroacetic acid. A recent summary45 indicates that some 10 fluorinated natural products have now been isolated (in small amounts) largely from other plant sources, their formation being rationalized from the metabolism of fluoroacetate. The exception is nucleocidin (1), an antibiotic from a microbial source (Streptomyces calvus), originating in an Indian soil sample, and which has a ribose moiety carrying fluorine at C4. 

Functionally and mechanistically reminiscent of the pyruvate lyases, the 2-deoxy-D-ribose 5-phosphate (121) aldolase (RibA EC 4.1.2.4) [363] is involved in the deoxynucleotide metabolism where it catalyzes the addition of acetaldehyde (122) to D-glyceraldehyde 3-phosphate (12) via the transient formation of a lysine Schiff base intermediate (class I). Hence, it is a unique aldolase in that it uses two aldehydic substrates both as the aldol donor and acceptor components. RibA enzymes from several microbial and animal sources have been purified [363-365], and those from Lactobacillus plantarum and E. coli could be induced to crystallization [365-367]. In addition, the E. coli RibA has been cloned [368] and overexpressed. It has a usefully high specific activity [369] of 58 Umg-1 and high affinity for acetaldehyde as the natural aldol donor component (Km = 1.7 mM) [370]. The equilibrium constant for the formation of 121 of 2 x 10M does not strongly favor synthesis. Interestingly, the enzyme s relaxed acceptor specificity allows for substitution of both cosubstrates propional-dehyde 111, acetone 123, or fluoroacetone 124 can replace 122 as the donor [370,371], and a number of aldehydes up to a chain length of 4 non-hydrogen atoms are tolerated as the acceptor moiety (Table 6). 

The sugar metabolism is a source of many enzymes, the transketolase (TK) being one of them. TK transfers an a-hydroxy carbonyl fragment from D-xylu-lose-5-phosphate onto D-ribose-5-phosphate, forming D-sedoheptulose-7-phos-phate and D-glyceraldehyde-3-phosphate (Scheme 5.14). Since this reaction is an equilibrium reaction and starting materials and products are of similar stability, it is not very versatile for organic synthesis. Fortunately TK also accepts pyruvate instead of xylulose. Under these modified circumstances carbon dioxide... 

Nucleotides are synthesized by two types of metabolic pathways de novo synthesis and salvage pathways. The former refers to synthesis of purines and pyrimidines from precursor molecules the latter refers to the conversion of preformed purines and pyrimidines—derived from dietary sources, the surrounding medium, or nucleotide catabolism—to nucleotides, usually by addition of ribose-5-phosphate to the base. De novo synthesis of purines is based on the metabolism of one-carbon compounds. 

The metabolism of pentoses has been studied in detail only recently, chiefly of ribose and to a lesser extent deoxyribose. Horecker and his coworkers (H7) have considered the steps in the hexose monophosphate shunt, and the pentose oxidative or Warburg-Dickens-Lipmann pathway. It appears that this pathway is the source of the pentose moiety of nucleotides, ribonucleic acid, and deoxyribonucleic acid. It is also undoubtedly the source of the small amounts of ribulose in normal urine. 

Nucleotides are formed directly from the aglycone by a phosphori-bosyl transfer involving PRPP (Reaction 1), or from the nucleoside by the phosphorylating action of a kinase (Reaction 2). Nucleosides may also be split by phosphorylases (Reaction 3) to yield the free base which may be recovered by Reaction 1, and ribose (or deoxyribose)- -phosphate which may be further metabolized as a carbon source. The nucleoside phosphorylases are primarily catabolic in function and, though reversible, they play little, if any, role in the normal utilization of free bases. The reversibility is limited by the availability of pentose phosphates and operates only under special conditions that allow accumulation of the pentose phosphates. 

Evidence from a number of sources indicated that pentose phosphates were metabolized in a series of reactions that resulted in the formation of hexose monophosphates and hexose diphosphates. Several enzyme steps are involved in these transformations. The reaction between D-ribulose 5-phosphate and D-ribose 5-phosphate to form D-sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate is catalyzed by an enzyme known as transketolase (91). This enzyme is found in plant, animal, and bacterial cells. Thiamine pyrophosphate (TPP) and Mg ions are required as cofactors. The mechanism of the reaction was suggested (92) as shown in reaction (28). 

The 2-deoxy-D-ribose 5-phosphate aldolase (RibA or DERA EC 4.1.2.4) is a class I enzyme that, in vivo, catalyzes the reversible addition of acetaldehyde to D-glyceraldehyde 3-phosphate (34 Figure 5.57) in the metabolic degradation of 127 from deoxyribonucleosides [269], ivith an equilibrium constant for synthesis of 2 x lO m [56]. It is, therefore, unique among the aldolases in that it uses an aldehyde rather than a ketone as the aldol donor. RibA has been isolated from eukaryotic and prokaryotic sources [270, 271],... 

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