Fructose, as is the case for other reducing sugars, undergoes the Maillard reaction with proteins and amino acids. The first stage of the reaction results in one or more substituted amino sugars. These products in turn enter the advanced and final stages of the Maillard reaction, which involve the formation of reactive intermediates, cross-linking of proteins, and the formation of brown and fluorescent polymeric materials. It would appear that the initial stages of the reaction occur more rapidly with fructose than with glucose. The Maillard reaction with any sugar, including fructose, results in a decrease in protein quality due to the loss of amino acid residues and decreased protein digestibility. Maillard products can inhibit the uptake and metabolism of free amino acids and of other nutrients such as zinc and some advanced Maillard products have mutagenic and/or anticarcinogenic properties. In vivo the Maillard reactions between proteins and fructose, glucose, and other reducing sugars may play a role in aging and in some of the clinical complications of diabetes.

The polyols are a family of bulk sweeteners, some of which are currently used in the United States and in other nations. The use of these compounds is likely to increase in the future. The greatest advantage of polyols as sweeteners is their reduced cariogenicity compared with sucrose, fructose, or glucose. This reduced cariogenicity has been observed with all of the polyols considered in this review. Furthermore, evidence suggests that one of these polyols, xylitol, may have cariostatic properties. More research is needed to clarify the mechanism of this cariostatic effect. Evidence suggests that moderate usage of the polyols in human diets over long periods is not likely to produce many toxic effects. This conclusion is supported by the facts that (a) both sorbitol and mannitol have been used as sweeteners for some time without apparent side effects, and (b) extensive long-term studies with dietary xylitol in Europe have not yielded any reports of toxicity. At this point there is no reason to believe that the disaccharide polyols differ significantly in a qualitative sense from sorbitol or mannitol with regard to their effects in humans. There are some research needs with regard to the inclusion of the polyol sweeteners in human diets: 1. All of the polyols can cause osmotic diarrhea in humans if higher levels are consumed. This fact is noted in the labelling of products containing mannitol and sorbitol in the United States (see "Current Regulatory Status"). If the disaccharide polyols are to be used as bulk sweeteners, further studies of the dose levels that can cause diarrhea may be needed. 2. The polyols, like other slowly absorbed carbohydrates, enhance the absorption of certain minerals, particularly divalent cations. More comparative and mechanistic studies of this effect are needed. 3. All of the polyols, lactose, and other slowly absorbed carbohydrates appear to cause adrenal medullary hyperplasia at high doses in laboratory rats. Evidence suggests that these lesions are linked in some way to the lactose or polyol-induced changes in calcium homeostasis. Despite long-term use of lactose, sorbitol, and mannitol in human diets, similar lesions in humans have not been reported and some investigators have concluded that the lesion in rats has no relevance to humans. Nevertheless further studies are needed to elucidate the mechanisms of the dietary lactose and polyol-induced adrenal hyperplasias in rats to ascertain definitively if they also operate in other species.(ABSTRACT TRUNCATED AT 400 WORDS)

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Several cyclic nucleotide derivatives with aminoalkyl side chains attached to the purine ring were synthesized and their interactions with adenosine 3',5'-monophosphate (cAMP) dependent protein kinase were studied before and after immobilization to CNBr-activated Sepharose 4B. The soluble N6-substituted derivatives were as effective as cAMP itself in activating protein kinase and were more effective than 8-substituted cAMP derivatives, whereas the 2-substituted cAMP derivatives and the cGMP derivatives were the least effective. All of the synthetic derivatives tested were poor substrates for beef heart phosphodiesterase being hydrolyzed at rates less than 2% for that of cAMP itself. Utilizing methodology developed to evaluate the affinity of protein kinase for immogilized cyclic nucleotides it was found that all of the immobilized cyclic nucleotides interacted with protein kinase in a biospecific manner as judged by the following criteria: (1) the immobilized cyclic nucleotides competed with cAMP for the binding sites on protein kinase; (2) the analogous spacer-arm did not compete; and (3) the effects of enzyme concentration, MgATP, and cleavage of the cyclic phosphate ring on the interactions of protein kinase with the immobilized cyclic nucleotides were the same as previously shown for free cAMP. In addition, the immobilized ligands were bound with the same order of effectiveness as the analogous soluble ligand. The observed Ka for the activation of 0.005 muM protein kinase by N6-H2N(CH2)2-cAMP was increased from 0.23 to 3 muM by the process of immobilization. This increase was unaffected by the coupling density and spacer-arm length. The observed Kb for 0.10 muM protein kinase binding to immobilized N6-H2N(CH2)2-cAMP was increased as the molecular sieving exclusion limit of the matrix used was decreased indicating that at least part of this decrease in apparent affinity upon immobilization is due to exclusion of the enzyme from a portion of the matrix and therefore of the immobilized ligand molecules.

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