Glucose monophosphate, synthesis

Triose, tetrose, and pentose phosphates enriched with C have been prepared by the Kiliani-Fischer reaction on the terminal phosphates of the next lower aldose. The mixed nitriles were separated on Dowex 1-X8 resin and reduced with hydrogen over Pd-BaS04. The synthesis of D-glucose 2-phosphate by phosphorylation of l,3,4,6-tetra-0-acetyl-j3-D-glucopyranosyl chloride, itself prepared by 2 1 acetyl migration, has been reported. Rates of phosphate hydrolysis in 0.25 M sulphuric acid and in 0.25 M sodium hydroxide were measured for D-glucose monophosphates in the former the order was 1-phosphate > 2-phosphate > 3-phosphate > 6-phosphate while in the latter it was 3-phosphate > 6-phosphate > 2-phosphate > 1-phosphate. ... 

Cells require a constant supply of N/ X)PH for reductive reactions vital to biosynthetic purposes. Much of this requirement is met by a glucose-based metabolic sequence variously called the pentose phosphate pathway, the hexose monophosphate shunt, or the phosphogluconate pathway. In addition to providing N/VDPH for biosynthetic processes, this pathway produces ribos 5-phosphate, which is essential for nucleic acid synthesis. Several metabolites of the pentose phosphate pathway can also be shuttled into glycolysis. 

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... 

Figure 20.10 The positions in the pathway for de novo purine nucleotide synthesis where GLUCOSE provides the ribose molecule and GLUTAMINE provides nitrogen atoms. The pathway begins with glucose which provides ribose 5-phosphate, via the pentose phosphate pathway (Chapter 6). Glutamine provides its amide nitrogen in two reactions formation of 5-phosphoribosylamine and formation of guanosine monophosphate (GMP) from xantho-sine 5-phosphate (XMP).

Activation of Gs or Gi proteins results in stimulation or inhibition, respectively, of adenylyl cyclase which catalyses the formation of cyclic adenosine monophosphate (cAMP) from ATP The cAMP binds to protein kinase A (PKA), which mediates the diverse cellular effects of cAMP by phosphorylating substrate enzymes, thereby increasing their activity. Among the responses mediated by cAMP are increases in contraction of cardiac and skeletal muscle and glycogenolysis in the liver by adrenaline (epinephrine). Because a single activated receptor can cause the conversion of up to 100 inactive Gs proteins to the active form, and each of these results in the synthesis of several hundred cAMP molecules, there is a very considerable signal amplification. For example, adrenaline concentrations as low as 10-10 M can stimulate the release of glucose sufficient to increase... 

Transketolase reactions leading via the pentose or hexose monophosphate shunt pathway of glucose oxidation to the eventual production of pentoses for RNA/DNA synthesis and NADPH for the biosynthesis of fatty acids... 

However, nucleoside diphosphates (NDP) are still expensive substrates, which can be obtained from much more cheaper nucleoside monophosphates (NMP). In this respect we have combined the SuSy-catalyzed cleavage of sucrose with the enzymatic formation of NDPs from NMPs catalyzed by nucleoside monophosphate kinase (NMPK, EC 2.7.4.4) or myokinase (MK, EC 2.7.4.3), including in situ regeneration of ATP with pyruvate kinase (PK, EC 2.7.1.40) (Fig. 20) [272]. Testing the substrate spectrum of four different kinases disclosed that none of them accepted dTMP as substrate [272], However, dUMP was well accepted by NMPK and dUDP-activated glucose could also substitute dTDP-activated glucose as precursor for the synthesis of activated deoxysugars (see below). The excellent enzyme stabilities under synthesis... 

Fig. 20. Enzymatic synthesis of activated glucoses (25,26,28,29) starting from nucleoside monophosphates and sucrose (24). A nucleoside monophosphate kinase (EC 2.7.7.4) or myokinase (EC 2.7.4.3), B sucrose synthase (EC 2.4.1.13)...

One is from glucose 1-phosphate and the other is from uridine monophosphate (UMP). The pyrophosphate that is liberated from the terminal phosphates of UTP is hydrolyzed to inorganic phosphate by the enzyme pyrophosphatase. This hydrolysis, which is irreversible, drives the reaction in the direction of UDP-glucose synthesis. 

The synthesis of Oj makes possible acceleration of glucose metabolism in the hexose monophosphate shunt, yielding NADP+, which is then used for dehydrogenation of glucose 6-phosphate to 6-phosphogluconic aldehyde (K15). 

The biosynthesis of PI in mycobacteria appears to be similar to that of the eukaryotic cells. " The de novo synthesis of Ino typically involves cyclization of glucose-6-P04, a reaction catalyzed by Ino-1-phosphate synthase (INOl, Rv0046c). " Ino-1-phosphate is then dephosphorylated by an Ino monophosphate phospha-... 

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