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Metabolic Cardiology
Published in Stephen T. Sinatra, Mark C. Houston, Nutritional and Integrative Strategies in Cardiovascular Medicine, 2022
As a pentose, ribose is not used by cells as a primary energy fuel. Unlike glucose which will provide a rapid energy source, ribose is preserved for the important metabolic task of stimulating purine nucleotide synthesis and salvage to produce ATP. Approximately 98% of consumed ribose is quickly absorbed into the bloodstream and is circulated to remote tissue with no first pass effect by the liver. As ribose passes through the cell membrane, it is phosphorylated by membrane-bound ribokinase before entering the pentose phosphate pathway downstream of the gatekeeper enzymes. In this way, administered ribose can increase intracellular PRPP concentration and initiate purine nucleotide synthesis and salvage.
Biosynthesis and Genetics of Lipopolysaccharide Core
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
David E. Heinrichs, Chris Whitfield, Miguel A. Valvano
The 343 N-terminal amino acids of the E. coli RfaE lack characteristics expected of sugar pyrophosphorylases but share strong conservation with members of the ribokinase family. Given these characteristics, it is possible that the pathway of synthesis of heptose involves a phosphotransfer step rather than a mutase reaction. In the Eidels and Osborn pathway, a mutase reaction transfers the phosphate group from carbon 7 to carbon 1 (Fig. 4A). In the alternative pathway proposed by Valvano et al. (51) (Fig. 4B), a new phosphate group would be added to carbon 1 and used later in the formation of the phosphodiester bond with ADP. If this is the case, the product of the second reaction should be d-glycero-d-manno-heptose-l,7-diphosphate. This alternative pathway will result in a heptose that will be phosphorylated at carbon 7. Interestingly, a phosphate group is found in at least two of the three heptoses isolated from E. coli LPS samples (see Fig. 2). It is therefore proposed that the rfaE gene product encodes a bifunctional protein acting in the intermediate steps of heptose biosynthesis.
Metabolic Cardiology
Published in Stephen T. Sinatra, Mark C. Houston, Nutritional and Integrative Strategies in Cardiovascular Medicine, 2015
As a pentose, ribose is not used by cells as a primary energy fuel. Unlike glucose, ribose is preserved for the important metabolic task of stimulating purine nucleotide synthesis and salvage for the production of ATP. Approximately 98% of consumed ribose is quickly absorbed into the bloodstream and is circulated to remote tissue with no first pass effect by the liver. As ribose passes through the cell membrane, it is phosphorylated by membrane-bound ribokinase before entering the pentose phosphate pathway downstream of the gatekeeper enzymes. In this way, administered ribose is able to increase intracellular PRPP concentration and initiate purine nucleotide synthesis and salvage.
Advances in biocatalytic and chemoenzymatic synthesis of nucleoside analogues
Published in Expert Opinion on Drug Discovery, 2022
Sebastian C. Cosgrove, Gavin J. Miller
Initially, the three key enzymes in the cascade (ribokinase [RK], phosphopentomutase [PPM] and purine nucleoside phosphorylase [PNP], Scheme 3A) were identified and engineered to improve their activity toward the non-natural dideoxyribose 4 (Scheme 3B). After optimizing the cascade to deliver 5, high concentrations of ATP were shown to be inhibitory to PPM, so an ATP recycling system was included (pyruvate kinase [PK], adenylate kinase [AK]). These enzymes convert the AMP and ADP that are produced during the RK phosphorylation of the sugar back into the ATP that is required for the RK step. This maintains sub-stoichiometric quantities of ATP, thereby avoiding inhibition of PMM.