Pyrophosphorylase action

DIETHYL PYROCARBONATE DEPHOSPHO-CoA KINASE Dephospho-CoA pyrophosphorylase, PANTETHEINE-RHOSRHATE ADENYLYL-TRANSFERASE DEPOLARIZATION ACTION ROTENTIAL HYPERROLARIZATION DEPOLYMERIZATION PROCESSIVITY... 

Several cases have been documented in which a different, naturally occurring, glycosyl phosphate substitutes for the true substrate of the pyrophosphorylase. Adenosine 5 -(a-D-xylopyranosyl pyrophosphate) was prepared by the action of the pyrophosphorylase of adenosine 5 -(a-D-glucopyranosyl pyrophosphate) from wheat flour,218... 

Certain therapeutic effects can be attributed to the inhibition of specific enzymic reactions. The inhibition of cholinesterase (Section 1.06.3), orotidylate pyrophosphorylase (Section 1.06.5) and of dihydrofolate reductase (Section 1.06.6.3) have already been discussed. They illustrate two modes of action, chemical alteration of the enzyme and competition with a substrate for the active site. 

The diastereomers of UTPaS and UDPaS-glucose can be separated by the action of yeast UDP-glucose pyrophosphorylase according to Equations 5 and 6 [21] ... 

In young developing leaves that still behave as sinks (rather than sources), sucrose is first hydrolyzed in the cytosol by the action of the invertase or by the sucrose synthase followed by UDPGIc pyrophosphorylase. The hexose sugars formed are then metabolized via glycolysis into C3 intermediates that are then transported into the chloroplast via the Pj translocator, where they can be used or stored as starch. 

In yeasts, the catalytic amounts of uridine 5-(D-glucosyl dihydrogen pyrophosphate) necessary could also be formed by the action of UDP-glucose pyrophosphorylase, which catalyzes the reaction ... 

From this brief survey, it is seen that there were few features of carbohydrate metabolism in plants that escaped Hassid s touch, and much that we now know about the role of sugar nucleotides in the interconversion of carbohydrates in plants is a direct result of his persistent effort. From the incorporation of labelled precursors into monosaccharides, to the conversion of the monosaccharides into their glycosyl phosphates, to the action of the pyrophosphorylases in the synthesis of glycosyl esters of nucleoside pyrophosphates, to the interconversion of the resulting sugar nucleotides, to the polymerization of the activated monosaccharides to yield disaccharides and the homopolysaccharides, and, finally, to the modification of the polysaccharides by methylation—in summary, to almost every aspect... 

In 1968, my graduate student Charles Walsh and I addressed the following question What are the pyrimidine sources for nucleic acid synthesis by Plasmodium lophurae We found the parasite synthesized pyrimidines de novo (Walsh and Sherman, 1968b). The evidence for a de novo synthesis was the presence of the key enzymes, thymidylate synthetase and oroti-dine-5-monophosphate pyrophosphorylase, as well as the demonstration of the incorporation of 14C-bicarbonate into cytosine, uracil and thymine. Finding a de novo pathway for the synthesis of pyrimidines by the malaria parasite would, in the next three decades, provide a biochemical basis for the mechanism of action of anti-folate anti-malarials as well as contributing to an understanding of the unique properties of the malaria parasite mitochondrion. 

The reverse phenomenon, decreased enzyme synthesis, can also be the mechanism of drug resistance. The antimetabolite pro-drug 6-mercaptopurine (6MP) is activated to its nucleotide by inosine-5 -phosphate pyrophosphorylase. The enzyme is deleted in resistant neoplastic cells. Resistance to 5-fluorouracil similarly develops by deletion of the enzyme converting this pro-drug to its active nucleotide. A mechanism of resistance by which a drug is excluded from its site of action can also be operative. This has been established for tetracycline antibiotics. Here the permeability of the cellular membrane to the drug is altered so that it cannot penetrate and accumulate within the target cell. Similarly, it has been demonstrated with such a membrane modification in MTX-resistant leukemia cells in mice. 

All susceptible fungi are capable of deaminating flucytosine to 5-fluorouracil, a potent antimetabolite that is used in cancer chemotherapy. Fluorouracil is metabolized fast to 5-fluorouracil-ribose monophosphate (5-FUMP) by the enzyme uracil phosphodbosyi transferase (UPRTase, also called uridine monophosphate pyrophosphorylase). As in mammalian cells, 5-FUMP then is either incorporated into RNA (via synthesis of 5-fluorouridine triphosphate) or metabolized to 5-fluoro-2 -5 deoxyuridine-5-monophos-phate (5-FdUMP), a potent inhibitor of thymidylate synthetase. DNA synthesis is impaired as the ultimate inhibition of this latter reaction. The selective action of flucytosine is due to the lack or low levels of cytosine deaminase in mammalian cells, which prevents metabolism to fluorouracil. 

The alginate pathway and the activities of the alginate enzymes overlap with a few other metabolic endpoints. The committed step in alginate biosynthesis is the formation of GDP-mannuronate. GDP-mannose is the precursor of GDP-rhamnose, a constituent of the A-band in lipopolysaccharide (EPS). The GDP-mannose that is required for A-band EPS biosynthesis is formed by the action of phosphomannose isomerase (PMI)/GDP-mannose pyrophosphorylase (GMP) activities that are separate from those used in... 

In liver, specific pyrophosphorylases catalyse the synthesis of nucleotides from free bases and 5-phos-phoribosyl 1-pyrophosphate alternatively, nucleosides may be formed first from bases and ribose 1-phosphate by the action of a nucleoside phosphoiy-lase (Fig.). Deoxynucleosides can be formed from bases and deoxyribose 1-phosphate by the action of deoxynucleoside phosphorylase. 

Thus the apparent existence of a UDPGal pyrophosphorylaae can be explained by the action of two other enzymes, and the occurence of uridine pyrophosphorylases other than that specific for UDPG remains uncertain. 

UDP-D-glucose pyrophosphorylase isolated from calf liver was extensively inhibited by the products of its action. ... 

The regeneration of GDP-Man has been employed in the synthesis of mannose-based oligosaccharides (Scheme 11) [35]. GDP-Man can be produced from Man-1-P and GTP by the action of GDP-Man pyrophosphorylase (GDPMP EC 2.7.7.22) in a manner analogous to previously described for NDP-sugars. The system described employed an al,2-mannosyltransferase (al,2-ManT) that was overexpressed in E. coli. The al,2-ManT accepted mannose, mannobiose, and O-mannosyl gly-copeptides as substrates. 

In the same fashion, GTP can be converted to GDP-Man as an intermediate in the recychng of GDP-Fuc (Scheme 12) [36]. This conversion can be accomplished by utilizing GDPMP from dried yeast cells and GDP-Fuc-generating enzymes partially purified from the bacterium Klebsiella pneumonia. This system must be coupled to an alcohol dehydrogenase (EC 1.1.1.2), which catalyzes the oxidation of 2-propanol to acetone, along with the reduction of NADP+ to NADPH. Alternatively, Fuc-l-P can be biosynthesized from fucose by the action of fucokinase (EC 2.7.1.52) from porcine liver in the presence of ATP (Scheme 13). Reaction of Fuc-l-P with GTP catalyzed by GDP-Fuc pyrophosphorylase (EC 2.7.7.30) then affords GDP-Fuc [37]. Both of these methods have been utilized in the synthesis of sLe from 3 -SLN. 

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