Chapter 5. Carbohydrates 1
Although fructose is a hexose (6 carbon sugar), it generally exists as a Definition: The D -enantiomer of fructose 1-phosphate. 5-dehydro-D-fructose. Mass. I am not sure what you are asking, but D-glucose and D-fructose are But D- fructose has a primary alcohol at C-1 and a ketone at C Common Name, D-Fructose Pure fructose has a sweet taste similar to cane sugar, but with a "fruity" aroma. D-lyxo-Hexulose, HMDB.
Fructose appears to increase uric acid levels in the blood to a higher extent than glucose, especially at high intakes and when consumed as excess energy [ 86, ]. An increased blood level of uric acid can theoretically lead to elevated blood pressure because uric acid inhibits an enzyme in the endothelial cells of the arteries called endothelial nitric oxide synthase eNOS.
Thus, inhibition of eNOS may lead to vasoconstriction. An average intake of fructose does not seem to lead to increased blood pressure [, ]. The lack of causal link between uric acid level and atherosclerosis makes it difficult to draw conclusions on this effect of fructose.
Type 2 Diabetes A high intake of sugar-sweetened beverages, with fructose as one of the major types of monosaccharides, has been associated with development of type 2 diabetes [ 5]. Although this association does not prove causation, it is important to study the role of fructose in the development of type 2 diabetes. Central to the understanding of type 2 diabetes is the effect of nutrients on blood glucose homeostasis.
Fructose must be converted to glucose in the liver to cause an increase in blood glucose level. As the conversion takes time and only a portion of the fructose will form glucose, fructose increases blood glucose less than similar levels of glucose [ 51 ]. Thus, the glycemic index for fructose is only 23 [ 10 ]. These effects are positive because they contribute to blood glucose homeostasis.
Additionally, moderate amounts of fructose have been shown to have positive effects on glycemic control [ 86, ]. However, it is claimed that fructose may also contribute negatively to blood glucose homeostasis by causing insulin resistance in the liver [ 9 ]. There is evidence that a high intake of fructose can cause insulin resistance in animals , but several human studies have failed to demonstrate such an association [— ].
The operational definition of insulin resistance or sensitivity seems unclear, and many different methods have been used to measure it [ ].
Thus, it is difficult to compare studies of insulin resistance. In human studies, in which fructose has been reported to cause insulin resistance, the daily intake of fructose has been as high as g [ ], approximately g [ ], 80 g [ ], and g [ 65 ].
This may indicate that the fructose intake must be high to potentially cause insulin resistance [ 86 ]. In the studies by Aeberli et al. Thus, the observed effect of fructose may also have been caused by differences in food intake between the control and experimental groups. In all the studies, in which insulin resistance has been shown, fructose was eaten together with glucose or starch, so the observations could also be the result of a combination of fructose and glucose.
A number of hypotheses on how fructose can cause insulin resistance in the liver have been proposed. Lipid accumulation in the liver [ — ], metainflammation [ 83 ], and oxidative stress [ ] are, either via inhibitory phosphorylation of the insulin receptor or the signaling molecules involved in insulin signaling, possible mechanisms for fructose-induced insulin resistance [ 9 ].
However, there are too few studies in humans and these are too divergent to be able to conclude firmly that there is a link between the consumption of fructose and insulin resistance. More long-term studies in which the daily intake of fructose is moderate are needed. Obesity It is debatable whether fructose is less satiating than other sugars and thus can contribute to obesity through a high food intake.
Journal of Nutrition and Metabolism
In a study by Page et al. Glucose, but not fructose, reduced activity regional cerebral blood flow in the hypothalamus in the areas involved in energy regulation and reward systems; this is probably an indicator of satiety and may indicate that fructose is less satiating than glucose.
Fructose will also to a lesser extent than glucose increase blood levels of insulin [ 51 ], leptin [ 51], gastric inhibitory polypeptide [ ], and glucagon-like peptide-1 [ 92 ], while at the same time it will attenuate levels of ghrelin less [ 51 ].
Although these hormonal effects may indicate that fructose is less satiating than glucose, this has not been confirmed in studies of the ability of fructose to satiate.
In such studies, it has been shown that fructose has a greater appetite-reducing effect than glucose, when intake occurs before a meal , or that there is no difference in the effects on appetite between fructose and glucose . Therefore, the effect of fructose on appetite remains unclear. Although it is conceivable that fructose, via lack of stimulation of satiety signals, could contribute to obesity, fructose has several properties that act against obesity.
As previously mentioned, the small intestine has a limited capacity to absorb fructose. This can lead to malabsorption at least if large amounts are consumed and consumption occurs without glucose-providing nutrients. Malabsorption of fructose will make less fructose enter the bloodstream and thus less energy will be available to the cells. In this way the malabsorption will act against obesity. It has also been shown in numerous studies that fructose has a greater thermogenic effect than glucose [ 46— ].
This means that the body uses more energy after eating fructose rather than glucose, so less energy will be available to be stored as fat. The relative sweetness of fructose is also greater than for glucose and sucrose . Although this will decrease with increasing temperature , the high relative sweetness allows smaller amounts of fructose than glucose and sucrose to be used to achieve a particular sweetness in most applications. On the basis of these properties, it does not appear that fructose is more fattening than other sugars.
This also agrees with experimental studies of the relationship between fructose intake and obesity in animals  and humans [ 6586, ]. Substrate Oxidation It has been proposed that fructose can inhibit lipid oxidation [ ]. For liver lipid oxidation this is logical, because the liver acquires energy from fructose and thus does not need to oxidize fat. Fructose can also increase DNL.
In some studies, however, fructose has been shown to increase the respiration quotient RQthe ratio of CO2 exhaled to O2 consumed, [ ] more than glucose. This indicates that fructose to a higher degree than glucose reduces total body lipid oxidation and increases total body carbohydrate oxidation.
Blaak and Saris [ ] conducted a study in which participants ate 75 g fructose, starch, or glucose after a hour fast in a crossover study. Fructose resulted in a significantly larger increase in the RQ, measured 6 hours after ingestion, than both glucose and starch. These results may be explained by the fact that fructose, more than glucose, enters DNL under specific conditions. Due to the fact that RQ varies for different substrates e.
Simultaneous occurrence of DNL and carbohydrate oxidation can lead to RQ values greater than 1 [ ]. An increased RQ caused by DNL can, therefore, be misinterpreted as reduced lipid oxidation and increased carbohydrate oxidation.
Such a misinterpretation may have occurred in the studies described above. Thus the effect of fructose on total body substrate oxidation remains unclear. Discussion The distribution of fructose into metabolic pathways, especially DNL, is of key importance to the health effects of fructose.
Individual physiological, enzymatic, and endocrine factors are also important. Diet composition and the amount of fructose eaten and absorbed will be the focus of this discussion.
Malabsorption of fructose will affect the amount of fructose absorbed and can thus be an important confounding factor in studies in which factors that affect absorption capacity have not been taken into account [ 39 ].
The results of studies in which fructose is malabsorbed can thus be inaccurate due to individual differences in the absorption capacity of fructose. As the small intestine has a large absorption capacity for glucose and a limited one for fructose, it is problematic to compare fructose with glucose as the sole carbohydrate source. In future studies, this should be controlled for, for example, by using the hydrogen breath test to assess fructose malabsorption. As fructose is present with glucose in most food products, it is more practical and relevant to look at the effects of fructose and glucose together than the effects of fructose alone.
A larger increase in DNL after eating fructose and glucose together This effect could be due to both increased absorption capacity for fructose when coingested with glucose and therefore greater availability of fructose carbon atoms going towards DNL and increased blood insulin levels when glucose is present in the diet. Insulin stimulates DNL directly and indirectly by inhibiting other important metabolic pathways for fructose, such as gluconeogenesis.
Insulin normally exerts its effects on hepatic energy metabolism via 2 metabolic pathways. Insulin's effects on maintaining euglycemia occurs through phosphorylation of the forkhead protein O1 FoxO1thus restricting it from entering the nucleus and preventing transcription of various gluconeogenic enzymes 14 Insulin also activates the lipogenic pathway by stimulating sterol regulatory element binding protein 1c SREBP-1cwhich activates the enzymes of de novo lipogenesis DNL to turn excess mitochondrial energy substrate into fatty acids, which are then linked to apolipoprotein B and packaged into VLDL for hepatic export.
However, metabolic syndrome does not result from complete hepatic insulin resistance 16 because this would result in hyperglycemia lack of FoxO1 phosphorylation and low serum VLDL lack of SREBP-1c activation. If there is only 1 insulin receptor, how can it activate 1 pathway and not the other 17?
To parse this dichotomy, the hepatic metabolism of glucose, ethanol, and fructose are considered in turn. Hepatic glucose metabolism Glucose is unique in that every prokaryotic and eukaryotic cell on the planet has the capacity to use glucose for energy. After oral consumption of glucose Fig. Insulin binds to its liver receptor, which promotes the tyrosine phosphorylation of insulin receptor substrate-1 IRS-1which increases the activity of phosphatidylinositol 3-kinase, inducing the transcription factor Akt responsible for insulin's intracellular metabolic effects.
This leads to the conversion of the majority of glucose molecules as hepatic glycogen for storage. The small amount that undergoes glycolysis reaches the mitochondria as pyruvate and is quickly esterified into acetyl-CoA. Figure 1 View large Download slide Hepatic glucose metabolism.
D-Glucose | C6H12O6 - PubChem
Under the action of insulin, glycogen synthase is increased, and the majority of the glucose load is stored as glycogen. Although insulin activation of sterol response element binding protein 1c SREBP-1c activates the lipogenic pathway, there is little citrate formed to act as a substrate for lipogenesis. In addition, insulin action on the liver phosphorylates forkhead protein O1 FoxO1excluding it from the nucleus, and suppressing the enzymes involved in gluconeogenesis GNG.
Reproduced from 59 with permission. Hepatic ethanol metabolism The hepatic pathway of ethanol metabolism is different from that of glucose in its regulation and the disposition of intermediary metabolites Fig. Biochemical properties[ edit ] Metabolism of common monosaccharides and some biochemical reactions of glucose Glucose is the most abundant monosaccharide. Glucose is also the most widely used aldohexose in most living organisms. One possible explanation for this is that glucose has a lower tendency than other aldohexoses to react nonspecifically with the amine groups of proteins.
Glucose's low rate of glycation can be attributed to its having a more stable cyclic form compared to other aldohexoses, which means it spends less time than they do in its reactive open-chain form. Presumably, glucose is the most abundant natural monosaccharide because it is less glycated with proteins than other monosaccharides. Polysaccharides that are composed solely of Glucose are termed glucans. Glucose is produced by plants through the photosynthesis using sunlight, water and carbon dioxide and can be used by all living organisms as an energy and carbon source.
However, most glucose does not occur in its free form, but in the form of its polymers, i. These polymers are degraded to glucose during food intake by animals, fungi and bacteria using enzymes.
All animals are also able to produce glucose themselves from certain precursors as the need arises. Nerve cellscells of the renal medulla and erythrocytes depend on glucose for their energy production. This complex of the proteins T1R2 and T1R3 makes it possible to identify glucose-containing food sources. Glucose mainly comes from food - about g per day are produced by conversion of food,  but it is also synthesized from other metabolites in the body's cells.
In humans, the breakdown of glucose-containing polysaccharides happens in part already during chewing by means of amylasewhich is contained in salivaas well as by maltaselactase and sucrase on the brush border of the small intestine. Glucose is a building block of many carbohydrates and can be split off from them using certain enzymes.
Glucosidasesa subgroup of the glycosidases, first catalyze the hydrolysis of long-chain glucose-containing polysaccharides, removing terminal glucose.
Showing metabocard for D-Fructose (HMDB0000660)
In turn, disaccharides are mostly degraded by specific glycosidases to glucose. The names of the degrading enzymes are often derived from the particular poly- and disaccharide; inter alia, for the degradation of polysaccharide chains there are amylases named after amylose, a component of starchcellulases named after cellulosechitinases named after chitin and more. Furthermore, for the cleavage of disaccharides, there are maltase, lactase, sucrase, trehalase and others. In humans, about 70 genes are known that code for glycosidases.
They have functions in the digestion and degradation of glycogen, sphingolipidsmucopolysaccharides and poly ADP-ribose. Humans do not produce cellulases, chitinases and trehalases, but the bacteria in the gut flora do. In order to get into or out of cell membranes of cells and membranes of cell compartments, glucose requires special transport proteins from the major facilitator superfamily.
With the help of glucosephosphataseglucosephosphate is converted back into glucose exclusively in the liver, if necessary, so that it is available for maintaining a sufficient blood glucose concentration. In other cells, uptake happens by passive transport through one of the 14 GLUT proteins.