Fructose Utilization Research Articles

Studies on the pharmacokinetics of carbohydrates as a basis for their use in parenteral feeding

Metabolic effects of glucose, fructose, sorbitol, xylitol and their combinations during intravenous application in men were investigated. The totale and metabolic clearance, the renal and metabolic elimination, the half-time and the turnover rate were measured. For all sugars intravenous long-term infusions from six to twelve hours were performed. Up to a dosage of 0.75 g/kg/h for glucose 0.5 g/kg/h for sorbitol and 0.25 g/kg/h for fructose and xylitol a steady state of substrates and metabolites has been found. If these dosage-limits are exceeded during glucose application a hyperglucosemia, after sorbitol a continous rise in sorbitol blood level, during fructose a rise in lactate and during xylitol infusion clinical side effects occurred. It could be shown that during simultaneous application of glucose, fructose and xylitol the utilization of glucose rises whereas the utilization of fructose and xylitol remain on such levels as if these sugar were infused alone.

Metabolic effect of a carbohydrate combination during simultaneous amino acid infusion

During a period of 12 hours, eight normal subjects were infused with an electrolyte containing combined 24% carbohydrate solution of fructose, glucose, and xylitol at a ratio of 2:1:1 (Triofusin E 1000 Pfrimmer) with a rate of supply of 0.6 gm/kg/h. Lamino acids (Aminofusin L 10% carbohydrate-free Pfrimmer) were simultaneously administered at a rate of 0.1 gm/kg/h. The serum substrate concentrations of fructose, glucose and xylitol and their excretion were measured. The utilization of fructose was 99%, of glucose practically 100% and of xylitol 88%. In accordance with the slight glucose increase, the concentration of insulin also showed an only slight increase. An increased serum concentration of oxalate was not observed. Despite the infusion of a glycine containing amino acid mixture, the excretion of oxalic acid even decreased during the infusion. The dilution effect measured by means of hematocrit, hemoglobin, erythrocyte count, total protein, and albumin was between 2 and 5%. The lactate concentration did not change significantly whereas hydroxy butyrate decreased significantly by the end of the infusion indicating the antiketogenic effect. A disturbance of fat metabolism was not observed as was indicated by the concentrations of neutral fat and cholesterol. The decrease of free glycerol cannot be clearly explained. A highly significant reduction of the serum uric acid concentration resulted from an increased renal elimination. The electrolyte concentrations of potassium, sodium, calcium and phosphate showed only slight modifications. The concentration of potassium initially rose significantly within normal ranges. Sodium and chloride remained constant whereas calcium decreased slightly but not significantly and phosphate decreased significantly until the 12th hour. The serum transaminase and bilirubin concentrations did not show any change. During the permanent infusion, a respiratory alkalosis developed. The average urinary excretion was 134 ml per hour, the excretion of potassium was 6 mEq/h, of sodium 15 mEq/h, and of phosphate 27 mg/h. The utilazation of a combined carbohydrate solution was in the same range with or without the simultaneous application of amino acids. The reduction of the uric acid concentration and the absent increase of lactate, bilirubin and oxalate may be considered as an additional desirable effect of the simultaneous application of amino acids.

Regulation of fructose uptake by glucose in Escherichia coli.

A mutant, DAI, has been isolated from the Escherichia coli K12, strain K2. 1t, as a colony resistant to 2-deoxyglucose (DG) when growing on fructose but still sensitive to DG when growing on other sugars. The mutation in DAI specifically affects the catabolite inhibition of fructose utilization by glucose and glucose-6-phosphate; the affected gene (designated cif) is located at min 41 on the E. coli linkage map and is highly co-transducible with the genes that specify the uptake of fructose (ptsF) and enzymic conversion of fructose-1-phosphate to fructose-1,6-bisphosphate (fpk).

Modification of human sperm metabolism by the induced release of intracellular zinc

Incubation of washed human spermatozoa in the presence of 6 mM histidine induces a release of about 75% of the zinc bound to the cells. Zinc release induced by the presence of histidine was accompanied by: 1) a significant increase in the utilization of exogenous 14C-labelled glucose, which is reflected in an increase in the production of 14CO 2, 2) a small but significant decrease (−14%) in the utilization of fructose when this sugar is added as exogenous substrate, and 3) a highly significant decrease in the endogenous sperm phospholipids (>30%), an effect which is not inhibited by the addition of exogenous substrates. This behavior of human spermatozoa resembles that previously described for invertebrate spermatozoa and seems to be related to the regulation of energy metabolism and probably to sperm capacitation.

X-ray dose response for mutation to fructose utilisation in cultured diploid human fibroblasts.

THE majority of studies relating to somatic cell mutation in cultured mammalian cells have been performed with established (heteronuclear) mammalian cells2. There are important karyotypic and metabolic differences, however, between cultured heteronuclear cells and mammalian cells in vivo and mutation in cultured diploid (homonuclear) cells may be more relevant to the in vivo situation. Mutation, in the broadest sense of the term1, has been studied in cultured diploid cells2–9 and there is evidence, from the work of Albertini and DeMars2 with 8-azaguanine resistant (Agr) variants of diploid human fibroblasts, that it may be possible to quantify radiation-induced mutation in diploid mammalian cells. Here we report that the utilisation of fructose, in place of glucose, as the major carbon and energy source, was used as a phenotypic character for mutation studies with a culture of diploid human fibroblasts. Although not yet fully understood, the fructose-utilisation mutation system does circumvent some of the problems of mutation expression time associated with the selection of Agr variants of cultured mammalian cells.

Utilization and turnover rate of fructose during continuous intravenous infusion in pre-term and term newborns in dependence on age.

Fructose turnover and utilization in dependence on age were examined in 55 pre-term and term newborns appropriate for gestational age during continuous intravenous infusion of fructose (0.25–1.0 g . kg<sup>––</sup><sup>1</sup> · h<sup>––1</sup>). (1) The linear turnover range of fructose is exceeded during the first 3 days of life independently of gestational age with infusions of 1.0 g · kg<sup>––1</sup> · h<sup>––1</sup>. This, however, is not the case in pre-term and term infants 10–12 days old. For the postnatal development of the fructose metabolism, the age of life is important, but not the gestational age. (2) During the first 3 days of life in pre-term and term infants, less than 10% of the fructose infused are eliminated. Thus, the fructose utilization is high even in the neonatal period, amounting to more than 90%. (3) The influence of fructose on the blood glucose concentration is not uniform and depends on fructose intake rate, gestational age, and age of life. Hypoglycemias were not observed.

A new coryneform hydrogen bacterium: Corynebacterium autotrophicum strain 7 C

1. Corynebacterium autotrophicum strain 7 C was isolated from an enrichment culture designed for propane oxidizing bacteria. The cells are Grampositive, immotile, short, irregularly formed rods. The colonies are yellow-pigmented and slimy. The yellow pigmentation is due to carotenoids. 2. Growth occurs either autotrophically in mineral medium under an atmosphere of 70% H2+20% O2+10% CO2 or heterotrophically with fructose or many organic acids as substrates. 3. The hexoses and gluconate are degraded via the Entner-Doudoroff pathway. 6-Phosphogluconate dehydrogenase is not detectable. 4. A NAD reducing hydrogenase has not been detected; the hydrogenase is localized in the particle fraction of the crude extract and reduces methylene blue. The specific activity of hydrogenase in the crude extract of autotrophically grown cells is 2400 μl H2/mg protein · hr. During growth on fructose the enzyme is constitutively formed (1200 μl H2/mg protein · hr). 5. The utilization of fructose was suppressed by hydrogen. The inhibitory effect was significant, when either fully adapted or autotrophically grown cells were exposed to a hydrogen containing atmosphere.

Ketohexokinase Activity in Whole Bovine Lenses and Single Lens Parts in Dependence on Age

The specific activity of ketohexokinase (EC 2.7.1.3), initiating the fructose utilization of lenses, depends upon age. In whole bovine lenses, this activity was found to be at a maximum at an age of about 9 months and, after subsequent decrease, the activity shows no further changes after an age of about 3 years. The highest activity at all ages investigated was found in the lens quator, with regional activities decreasing therefrom in the order: anterior cortex, posterior cortex and nucleus. The age dependency of ketohexokinase activity in the different lens parts differs from that of the whole lens. During ageing, there is an increase in specific activity in the equator; anterior and posterior cortex show almost constant values and the activity of the lens nucleus steadily decreases. The importance of these findings is discussed with respect to the age-induced changes in the lens carbohydrate metabolism.

Evidence for the in vivo regulation of glucose 6-phosphate dehydrogenase activity in Hydrogenomonas eutropha H 16 from measurements of the intracellular concentrations of metabolic intermediates.

The inhibition of fructose utilization by whole cells of Hydrogenomonas eutropha H 16, following the addition of hydrogen to the gas phase, has been explained as an inhibition of glucose 6-phosphate dehydrogenase (Blackkolb and Schlegel, 1968a, b). The intracellular concentrations of glucose 6-phosphate, 6-phosphogluconate, three inhibitors of the enzyme (NADH, ATP and phosphoenolpyruvate) and some related metabolites were measured in cells incubated in the presence and absence of hydrogen. Inhibition of glucose 6-phosphate dehydrogenase was confirmed by an increase in the glucose 6-phosphate pool and a decrease in the 6-phosphogluconate concentration. The regulatory control is apparently due to a threefold increase in the NADH concentration while the concentrations of the other two inhibitors fell slightly. When the measured intracellular concentrations of intermediates were used in the in vitro assay of glucose 6-phosphate dehydrogenase activity, an almost total inhibition of the dehydrogenase was observed, therefore further regulatory factors must be considered.

Utilization of fructose by a unicellular blue-green alga, Anacystis nidulans.

Utilization of fructose by a unicellular blue-green alga, Anacystis nidulans.

Inhibition by 3-deoxy-3-fluoro-D-glucose of the utilization of lactose and other carbon sources by Escherichia coli.

Summary: 3-Deoxy-3-fluoro-D-glucose (3FG) was converted to 3FG-6-phosphate by the phosphoenolpyruvate-dependent phosphotransferase system in frozen and thawed Escherichia coli. Up to 0.03g 3FG was taken up/g bacterial dry wt. Uptake of 3FG was not lethal, though 3FG at 0.1 to 10 mM completely prevented or severely inhibited utilization of lactose, fructose, glycerol, succinate, acetate and pyruvate. It prevented lactose utilization by inhibition of the synthesis and activity of both β-galactosidase and galactoside permease. 3FG-resistant mutants were isolated which were deficient in the Enzyme II of the phosphoenolpyruvate-dependent phosphotransferase system specific for glucose and for 3FG. Our findings support the view that the ‘glucose effect’ may depend upon glucose itself or a glucose derivative, rather than upon catabolic products.

Utilization of gluconate by Escherichia coli. Induction of gluconate kinase and 6-phosphogluconate dehydratase activities

1. A mutant of Escherichia coli, devoid of phosphopyruvate synthetase, glucosephosphate isomerase and 6-phosphogluconate dehydrogenase activities, grew readily on gluconate and inducibly formed an uptake system for gluconate, gluconate kinase and 6-phosphogluconate dehydratase while doing so. 2. This mutant also grew on glucose 6-phosphate and inducibly formed 6-phosphogluconate dehydratase; however, the formation of the gluconate uptake system and gluconate kinase was not induced under these conditions. 3. The use of the Entner-Doudoroff pathway for the dissimilation of 6-phosphogluconate, derived from either gluconate or glucose 6-phosphate, by this mutant was also demonstrated by the accumulation of 2-keto-3-deoxy-6-phosphogluconate (3-deoxy-6-phospho-l-glycero-2-hexulosonate) from both these substrates in a similar mutant that also lacked phospho-2-keto-3-deoxygluconate aldolase activity. 4. Glucose 6-phosphate inhibits the continued utilization of fructose by cultures of the mutants growing on fructose, as it does in wild-type E. coli. 5. The mutants do not use glucose for growth. This is shown to be due to insufficiency of phosphopyruvate, which is required for glucose uptake.

The utilization of fructose by Escherichia coli. Properties of a mutant defective in fructose 1-phosphate kinase activity.

1. The isolation and properties of a mutant of Escherichia coli devoid of fructose 1-phosphate kinase activity are described. 2. This mutant grew in media containing any one of a variety of substances, including hexoses, hexose 6-phosphates, sugar acids and glucogenic substrates, at rates not significantly different from those at which the parent organism grew on these substrates. However, only the parent grew on fructose or fructose 1-phosphate. 3. Fructose and fructose 1-phosphate inhibit the growth of the mutant, but not of its parent, on other carbon sources. 4. Even though not previously exposed to fructose, the mutant took up [(14)C]fructose rapidly but to only a small extent: [(14)C]fructose 1-phosphate was identified as the predominant labelled product. In contrast, the equally rapid but more extensive uptake of [(14)C]fructose by the parent organism required prior growth in the presence of fructose.

病鰻から分離された <i>Edwardsiella tarda (Paracolobactrum anguillimortiferum</i>) の性状

Morphological and biochemical characteristics of 22 strains of an enteric bacterium isolated from diseased pond-cultured eels in Shizuoka Prefecture in 1972 were examined. These organisms were gram-negative, peritrichously flagellated rods. They gave negative oxidase reaction, utilized glucose fermentatively in Hugh-Leifson's medium and reduced nitrate to nitrite. Some distinguishing features of the organisms were the produc-tion of hydrogen sulfide and indol, positive to methylted test, negative to Voges-Proskauer test, no growth on Simmons' citrate agar, growth on Christensen's citrate agar, decarboxi-lization of lysine and ornithine, and utilization of fructose, galactose, mannose, maltose, and glycerol (Table 1). All of the strains examined were sensitive to dihydrostreptomycin and kanamycin, but some of them were resistant to chloramphenicol, tetracycline and colistin (Table 2). The above properties suggest that the organism should be identified as Edwardsiella tarda, with which Paracolobactrum anguillimortiferum is thought to be synonymous.

Biochemical and metabolic function of the canine liver after four hours preservation.

AbstractCanine livers were stored for four hours with either hypothermia alone, hypothermia and low flow electrolyte perfusion, hypothermia low flow plasma perfusion, or normothermic dilute blood perfusion. The livers were evaluated by a subsequent two hour normothermic dilute blood test perfusion. Pressure flow relationships were of value in assessing the adequacy of the storage, and correlated well with glucose production and ultrastructural appearances. Livers stored with plasma perfusion seemed to be the most satisfactory. Anaerobic utilization of fructose was a more sensitive index of cellular damage than oxygen uptake in manometric studies. Bromsulphthalein clearance during the test perfusion was of limited value.

CULTIVATION CONDITIONS AND EXPRESSION OF "FRUCTOSE EFFECT" IN ACTINOMYCES ROSEOFLAVUS VAR. ROSEOFUNGINI

Actinomyces (Streptomyces) roseoflavus var. roseofungini which yields secondary nocardioform colonies when grown on synthetic medium with D-fructose as sole carbon and energy source ("fructose effect") was employed as test organism in screening for conditions and compounds which enhance or retard the fructose effect.The results of alterations in cultivation conditions point to the importance of fructose being metabolized for its effect to be observed. The effective individual compounds tested were tentatively grouped as follows: (1) Strongly inhibitory in high concentrations for the growth of actinomycete while retarding emergence of secondary colonies against the background of weak growth in moderate or low concentrations (most antibiotics and some enzyme inhibitors, phenol, indole, anthranillic acid, indolyl-acetic acid, sodium hydrosulphite, iron salts). (2) Non-inhibitory for growth (occasional stimulation noted), retarding emergence of secondary colonies, a) Active in low concentrations (mannitol, tyrosine, shikimate, oxalate, alanine, valine, norvaline, leucine). b) Active in high concentrations (glucose, galactose, glycerol, ascorbate, citrate, lactate, several amino acids). (3) Non-inhibitory for growth with slight tendency to enhance emergence of secondary colonies (fumarate, malate, succinate, phenylalanine, sodium chloride). Compounds of group 3 neither individually nor in combinations were able to substitute fructose in its capacity to elicit secondary growth. Some treatments (increase in incubation temperature, addition of methionine) tended to increase the relative number of secondary colonies of diminished size. The results are discussed in relation to the possibility that emergence of secondary colonies is due to some "abnormalities" in fructose metabolism, leading to production of metabolites which induce and/or select particular type of mutants. Among effective additives some (mannitol) probably affect the fructose metabolism itself, while others "cure" the lesions due to its "peculiarity" or improve the efficiency of fructose utilization.

Factors affecting hexose phosphorylation in Acetobacter xylinum.

Fructose was oxidized and converted to cellulose by cells of Acetobacter xylinum grown on fructose or succinate, but not by cells grown on glucose. In resting fructose-grown cells, glucose strongly suppressed fructose utilization. Extracts obtained from fructose- or succinate-grown cells catalyzed the adenosine triphosphate (ATP)-dependent formation of the 6-phosphate esters of glucose and fructose, whereas glucose-grown cell extracts phosphorylated glucose but not fructose. Fructokinase and glucokinase activities were separated and partially purified from cells grown on glucose, fructose, or succinate. Whereas fructokinase phosphorylated fructose only, glucokinase was active towards glucose and less active towards mannose and glucosamine. The optimal pH for the fructokinase was 7.4 and for the glucokinase was 8.5. The K(m) values for the fructokinase were: fructose, 6.2 mm; and ATP, 0.83 mm. The K(m) values for the glucokinase were: glucose, 0.22 mm; and ATP, 4.2 mm. Fructokinase was inhibited by glucose, glucosamine, mannose, and deoxyglucose in a manner competitive with respect to fructose, with K(i) values of 0.1, 0.14, 0.5, and 7.5 mm, respectively. Adenosine diphosphate (ADP) and adenosine monophosphate (AMP) inhibited both kinases noncompetitively with respect to ATP. The K(i) values were: 1.8 mm (ADP) and 2.1 mm (AMP) for fructokinase, and 2.2 mm (ADP) and 9.6 mm (AMP) for glucokinase. Fructose metabolism in A. xylinum appears to be regulated by the synthesis and activity of fructokinase.

Abnormal carbohydrate metabolism in patients with liver cirrhosis; in vitro study.

The serum of patients with liver cirrhosis inhibits glucose utilization in rat diaphragm. Inhibition is not caused by increased glycogenolysis or decreased glycogen synthesis. Lactate production and fructose utilization are not changed, indicating that the inhibition of glucose utilization is localized at the level of transmembrane transport of glucose or at the level of hexose phosphates. The inhibitory activity of cirrhotic serum, fractioned by gel filtration moves with peptides and aminoacids, excluding the significance of FFA and of growth hormone.

The effect of fructose on hepatic synthesis of fatty acids.

Abstract. The synthesis of fatty acids from fructose and glucose has been compared in rat and human liver. In both species fructose is a better precursor of fatty acids than glucose, primarily as a result of the greater rate of glycolysis of fructose as compared to glucose. The high rate of fructose utilization and relatively low rates of glucose utilization by liver is reflected by the activity of fructokinase which is considerably greater than the total hexokinase and glucokinase activities. Although it is not possible to exclude that the high rate of fructolysis produces a metabolic intermediate which alters the functional state of the fatty acid synthesizing enzymes, the experimental evidence indicates that hepatic fatty acid synthesis in carbohydrate‐fed animals is limited by the supply of substrate. Because the hepatic metabolism of fructose can supply acetyl CoA to the fatty acid synthesizing enzymes at greater rates than can glucose, hepatic fatty acid synthesis is enhanced in fructose‐ or sucrose‐fed animals. Since estimates of maximum rates of fatty acid synthesis in human liver based on in vitro measurement of the activity of acetyl‐CoA carboxylase suggest that de novo synthesis of fatty acids in human liver can be large in comparison to the turnover of triglycerides in very low density lipoproteins, the data are compatible with the conclusion that enhanced rates of hepatic fatty acid synthesis contribute significantly to fructose‐ or sucrose‐induced hypertriglyceridemia in normal men.

Fructose in medicine. A review with particular reference to diabetes mellitus.

Summary A review is given of the metabolism of fructose in the mammalian organism, and its significance in medicine. Emphasis is laid upon the absorption and assimilation of fructose through pathways not identical with those of glucose. The metabolism of fructose is largely insulin-independent, although the ultimate fate of fructose carbons is determined by the presence or the absence of insulin. Clinical and experimental work has suggested that fructose may exert beneficial effects as a component of the diet for patients with mild and well-balanced diabetes. Fructose is absorbed slowly from the gut, and does not induce drastic changes in blood sugar levels. Secondly, fructose is metabolized by insulin-independent pathways in the liver, intestinal wall, kidney and adipose tissue. As a consequence of the rapid and efficient utilization of fructose, it has been used widely for intravenous feeding in medicine and surgery. However, it has been shown that the rapid infusion of large amounts of fruetose may cause accumulation of lactic acid in the extracellular fluid. The possibility of lactate acidosis, with concomitant impairment of the acid-base balance, already disturbed, constitutes a relative contraindication to the use of intravenous fructose in the treatment of diabetic ketoacidosis. Fructose is known to accelerate ethanol metabolism in the liver. No well-documented reports on the use of fructose in the treatment of ethanol intoxication have been published, although it has recently been suggested that fructose might be of value in the treatment of delirium tremens. Fructose may be less cariogenic than sucrose, at least in short-term experiments. Long-term trials are lacking, and thus the potential advantages of fructose in preventive odontology have not been determined. Fructose does not seem to have any side-effects when used in reasonable amounts. However, it has been reported that the administration of fructose in large amounts induces hyperlipidemia both in man and in experimental animals. Earlier suggestions concerned with the atherogenic properties of fructose have recently been challenged. The apparent increase in the incidence of coronary disease among sucrose users seems to be a statistical artefact, caused by the increased ingestion of coffee and soft drinks by cigarette smokers.