Sugar transfer mechanism

Wick and Drury, 1953 Haft et al., 1953 Park, 1953 Ross, 1953). Thus, there is general agreement that one site, but not necessarily the only site, of insulin action is upon a sugar transfer mechanism. 

It is possible that the sugar transfer mechanism upon which insulin acts might involve the mesenchymal ground substance which surrounds each cell. It should be noted that the transport of metabolites through the ground substance is very poorly understood. 

The kinetics and mechanisms of the oxidation of DNA, nucleic acid sugars, and nucleotides by [Ru(0)(tpy)(bpy)] and its derivatives have been reported. " The Ru =0 species is an efficient DNA cleavage agent it cleaves DNA by sugar oxidation at the 1 position, which is indicated by the termini formed with and without piperidine treatment and by the production of free bases and 5-methylene-2(5//)-furanone. Kinetic studies show that the I -C— activation is rate determining and a hydride transfer mechanism is proposed. The Ru =0 species also oxidizes guanine bases via an 0x0 transfer mechanism to produce piperidine-labile cleavages. 

Hydride-Transfer Reactions. The hydride-transfer mechanism for rearrangement of sugars (20) yields a ketose anion (5) by direct transfer of the C-2 hydrogen atom with its electrons to C-l. Reversal of the process leads to epimerization at C-2 (Scheme II). 

The mechanism of UGM is of great interest and is still not completely resolved. Both a single-electron transfer mechanism and a nucleophilic mechanism have been proposed (Scheme 28). Both mechanisms involve the formation of a substrate—flavin N5 adduct, which has been trapped during turnover. This could arise due to direct nucleophilic attack of the reduced flavin on the sugar substrate. Alternatively, this adduct could arise from one-electron transfer from the reduced flavin to an oxocarbenium ion generated by elimination of UDP, followed by radical recombination of the flavin semiquinone and hexose radical. " An oxocarbenium ion is a proposed intermediate based on positional isotope exchange experiments and studies with substrate analogues, possible. 

FIGURE 27.6 Schematic of a chained carrier PIM transfer mechanism of a sugar in the case of (a) fixed and (b) locally mobile canier particles (TOMA ion-pairs). (Reprinted from Sol. Extr. Res. Dev. Jpn., 16, O Rourke, M., Cattrall, R.W., Kolev, S.D., and Potter, I.D., The extraction and transport of organic molecules using polymer inclusion membranes, 1-12, Copyright 2009, with permission from Elsevier.)... 

Examination of the formulas of the insulin-sensitive sugars reveals that all have a similar configuration in carbons 1, 2, and 3. These considerations brought Levine to conclude that sugar transport does not occur by simple diffusion but through a specific insulin-sensitive transfer mechanism. 

The mechanism of direct participation of retinoids in the transfer of mannose to glycoconjugates is appealing in light of the broad implications of changes in cell surface glyconjugates in control of cell growth, differentiation, and transformation (see Section VI). However, firm conclusive evidence must still be provided to demonstrate a role for retinoids distinct from that of dolichol. Furthermore, a satisfactory metabolic scheme for the direct participation of retinoic acid and its derivatives in sugar transfer reactions does not yet exist. Future experiments must be addressed to these two important questions. 

Since the initial publication of this series of observations (Levine et al., 1950), a host of data from a variety of experimental approaches both in vitro and in vivo have fully confirmed the basic contention of their thesis that insulin is concerned with accelerating a transfer mechanism, independent of the hexokinase reaction, which facilitates the passage of glucose and other sugars like galactose across cytostructural barriers... 

In this process there is no net exchange of ions between the cell and its surroundings. The membrane component that complexes with the ion discharges that ion into one phase, and then takes up from that phase another ion of the same species. This exchange-diffusion type of mechanism has been experimentally observed for sugar transfer reactions, for amino acids and for inorganic ions. 

In 1983 Prehm [36] proposed a mechanism by which HA is synthesized on the interior side of the plasma membrane by addition of intact UDP-sugars to the reducing end of the chain and concommittant release of the UDP attached to the chain in the preceeding sugar transfer. The non-reducing end of the chain was translocated through the membrane into the pericellular space. The evidence for this mechanism was the following ... 

FIGURE 10.27 The path of the phosphoryl group through the PTS mechanism. Reactive phosphohistidine intermediates of Enzyme I, HPr, and Enzyme III transfer phosphoryl groups from PEP to the transported sugar. 

The emphasis in kinetic studies of E-IIs has been on the analysis of the rates of phosphorylation of the sugar by the phosphoryl group donor. In the early studies the question was addressed whether phosphorylated E-II would be a catalytic intermediate in the reaction or whether the phosphoryl group would be transferred directly from the donor to the sugar on a ternary complex between the enzyme and its substrates [66,75,95-100]. This matter has been satisfactorily resolved by a number of other techniques in favor of the first option and possible reasons why some systems did not behave according to a ping-pong type of mechanism have been discussed [1]. 

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