Key words fructose, fructose metabolism, fructose sup. However, the liver is the main site of fructose metabolism, where fructose is converted to fructose1phosphate, thereby proving that it is not subject to. Oct 02, 2012 the metabolism of food derived sucrose, fruit sugars, honey, and high fructose corn syrup, major sources of fructose and glucose in the diet, are currently under study, and the biological effects resulting from the use of experimentally formulated mixtures of glucose and fructose are relevant to our understanding. Sooad aldaihan biochemistry department fructose metabolism diets containing large amounts of sucrose a disaccharide of glucose and fructose can utilize the fructose as a major source of energy. In the other diet, fructose, and carbohydrate energy was. How sugar causes obesityexplaining the difference in glucose vs. The liver converts approximately 2954% of fructose into the byproducts of glycolysis, which can undergo regular metabolism, the same as the dietary glucose by converting into pyruvate. The utilization of fructose as sole carbon source for the growth of escherichia coli beautifully illustrates this metabolic flexibility. There is overwhelming evidence that an overconsumption of sucrose or of fructose can produce deleterious metabolic effects. Fructose metabolism fructose metabolism differs from that of glucose in 2 major ways. Intermediary fructose metabolism fructose concentrations in peripheral plasma are typically about 0.
Because higher doses of fructose overwhelm the small intestine and spill over to the liver, it is tempting to speculate that fructose metabolism in the small intestine is safe physiologic, whereas fructose metabolism in the liver drives metabolic disease pathologic, at least for individuals with consistent access to abundant highcalorie foods. Cell metabolism article aldolase bmediated fructose metabolism drives metabolic reprogramming of colon cancer liver metastasis pengcheng bu,1,2,3,9, kaiyuan chen,3,9 kun xiang,3,9 christelle johnson,4,5,9 scott b. In the liver time enzyme fructokinase phos pimorylates fructose to fructoseiphosphate. The main difference between glucose and fructose metabolism is that glucose can readily enter glycolysis whereas fructose first converts into the byproducts of the glycolysis, which then undergo cellular respiration by entering through the krebs cycle. An ancient mutation in apes that explains why humans turn fructose into fat so easily 23. Fructose metabolism and metabolic disease dukespace. Aldolase b also functions in the liver for normal glycolysis glucose metabolism. Fructose, or fruit sugar, is a simple ketonic monosaccharide found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. Aug 22, 2019 these data highlight the role of intestinal chrebp for fructoseinduced impaired metabolism.
Pdf clinical research strategies for fructose metabolism. Fructose metabolism and metabolic disease ncbi nih. Nov 28, 2014 metabolism of excess fructose, which is metabolized differently than glucose, is a general major disaster for human health. Most important, a significant amount of ingested fructose is converted to glucose figure 1.
You will need to read food labels and learn which foods are high in fructose. Fructose in the bloodstream is utilized about twice as fast as blood glucose. Metabolic disease metabolic disease disorders of carbohydrate metabolism. Fructose metabolism disorders are one of the many carbohydrate metabolism disorders. Fructosedriven glycolysis supports anoxia resistance in the. Fructolysis and glycolysis are independent pathways. Research design and methods six type i and 12 type ii diabetic subjects consumed, in random order, two isocaloric study diets for 28 days. Themajorrouteof fructose metabolism and vegetables. Fructose metabolism an overview sciencedirect topics. When ingested by itself, fructose is poorly absorbed from the gastrointestinal tract, and it is almost entirely cleared by the liverthe circulating concentration is.
Fructose metabolism in humans what isotopic tracer studies. Fructose forms complexes with metal ions and hence may modulate the intestinal absorption and bioavailability of minerals. The major concerns in fructose metabolism synthesis of glycerol3phos. Sugar in the form of sucrose or highfructose corn syrup, both of which are composed of nearly equal amounts of glucose and fructose, is added. Moreover, the conversion of external fructose to fructose 1,6bis. Fructosecontaining caloric sweeteners as a cause of obesity. Therefore, understanding the mechanisms underlying intestinal and hepatic fructose metabolism. Intermediary metabolism of fructose the american journal. For liver a metabolic pathway for fructose has been described in which the ketosugar is phosphorylated by ketohexokinase to fructose.
Fructose absorption is mainly mediated by glucose transporter 5 glut5, a fructose transporter expressed on the apical border of enterocytes in the small intestine across the. To this end, we focus on understanding molecular and cellular mechanisms of fructose and. Metabolic effects of fructose and the worldwide increase. Dietary fructose and the metabolic syndrome calorie. Though the metabolism of glucose through glycolysis uses many of the same enzymes and intermediate structures as those in fructolysis, the two sugars have very different metabolic fates in human metabolism. Crystalline fructose adopts a cyclic sixmembered structure owing to the stability of its hemiketal and internal hydrogenbonding.
Fructose utilization and associated metabolic dysfunction. Fructolysis is prominent in the kidney, which expresses high levels of both the more fructose selective khkc isoform and the lessefficient khka isoform 17 20. Dfructose o hoh ho h ho h ch 2oh ch 2oh lfructose the ability of humanproduced enzymes to digest these carbohydrates. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into blood during digestion. Furthermore, glucose metabolism occurs in the cells throughout the body while the conversion of fructose into glucose byproducts occurs in. Fructose is a natural sugar found in many foods like fruits and honey. It is then metabolized to intermediates of glycolysis.
Celep gs, rastmanesh r, bozoglu f 2015 fructose metabolism and health risks. Consumption of soft drinks high in hfcs is associated with an increased risk for obesity in adolescents and for type 2 diabetes in young and middleaged women. Fructolysis is prominent in the kidney, which expresses high levels of both the more fructoseselective khkc isoform and the lessefficient khka isoform 17 20. Pdf increased sugar consumption is increasingly considered to be a contributor to the worldwide epidemics of obesity and diabetes and their. Most of the metabolic effects of fructose are due to its rapid utilization by the liver and it bypassing the phosphofructokinase regulatory step in glycolysis, leading to far reaching consequences to carbohydrate and lipid metabolism. The first step in the metabolism of fructose is the formation of fructose 1. Nov 15, 2018 the intestine absorbs fructose in the food and it travels to the liver through the bloodstream. First, there is nearly complete hepatic extraction of fructose. However, the liver is the main site of fructose metabolism, where fructose is converted to fructose 1phosphate, thereby proving that it is not subject to. Fructose absorption is mainly mediated by glucose transporter 5 glut5, a fructose transporter expressed on the apical border of enterocytes in the.
Metabolism of fructose in liver heinz 1972 acta medica. The liver is considered to be the major organ for fructose metabolism 16,25,26,27. Longterm studies are still needed to ascertain that longterm fructose supplementation has a sustained beneficial effect in diabetes and is devoid of deleterious side effects. In one diet, 20% of energy was derived from fructose. Intermediary metabolism of fructose the american journal of. Unlike glucose, which is directly metabolized widely in the body. Most people have trouble with large amounts of fructose like in high fructose corn syrup and honey rather than smaller amounts of fructose in fruit. Fructose has the same chemical formula as glucose c6h12o6, but its metabolism differs markedly from that of glucose due to its almost complete hepatic extraction and rapid hepatic conversion into glucose, glycogen, lactate, and fat.
The metabolic effects of free fructose, as in high. Essential fructosuriais a harmless anomaly characterized by the appearance of fructose in the urine after. Metabolic fate of an oral fructose load in healthy subjects 28 e. Metabolic effects of dietary fructose in diabetic subjects. Its metabolism takes place in the liver, where fructose is converted to pyruvate, or under fasting conditions to glucose. Fructose metabolism disorders pediatrics msd manual. Fructose metabolism and relation to atherosclerosis, type 2.
Under normal dietary intake the majority of the ingested fructose is metabolized by the enterocytes of the small intestine primarily to glucose which is then delivered to the systemic circulation. The association between uric acid and insulin resistance raised the interest of uric acid as a potential biomarker in metabolic syndrome and several studies have established that serum. Barth,3 min lu,8 ziyang gao,3 robert mines,3 liwen zhang,1,2 mark. Diabetes mellitus and the metabolic syndrome are becoming leading causes of death in the world. Fructose metabolism by enterocytes contributes to firstpass splanchnic fructose extraction, but the relative contributions of the human gut and liver in this process are not yet known. The worldwide epidemics of obesity and diabetes have been linked to increased sugar consumption in humans. The conundrum for understanding fructose metabolism is how a carbon in. Fructose absorption ingested fructose is predominantly absorbed passively from the intestinal lumen via the hexose transporter slc2a5, also known as. This rapid clearance is mediated in large part by efficient extraction by.
High amounts of fructose going to the liver to be metabolized disturbs glucose metabolism in the liver as well as uptake pathways and levels of metabolic pathways that are associated with creating insulin resistance. A large body of evidence associate consumption of fructose and. First, there is nearly complete hepatic extraction of fructose, and second, as shown in. Fructose is metabolized almost completely in the liver in humans, and is directed toward replenishment of liver glycogen and triglyceride synthesis, while much of dietary glucose passes. The small intestine converts dietary fructose into glucose and. Although fructose and glucose are both monosaccharides with closely similar formulas, their metabolism pathways are divergent in both enterocytes and in hepatocytes 14,15,16,17. Routes for fructose utilization by escherichia coli. Generally deleterious effects of administering fructose alone suggest that fructose metabolism is normally controlled in part by glucose. The metabolism of the carbohydrates galactose, fructose, and glucose is intricately linked through interactions between different enzymatic pathways, and disorders that affect these pathways may have symptoms ranging from mild to severe or even lifethreatening. Dietary fructose and the metabolic syndrome fructosefacts. Monosaccharide d and l series when looking at a monosaccharide as a straight chain, the position of the hydroxyl group on the asymmetric 58 chapter 3 carbohydrates. Metabolic fate of an oral load of fructose in diabetic patients 29 f. Jul 10, 2019 the relationship between fructose metabolism mediated hyperuricemia and development of the metabolic syndrome can also be demonstrated by the fact that treating animals with allopurinol, a drug used to lower uric acid levels in gout patients, partially prevented the fructose induced metabolic syndrome. New insights in our knowledge of intestinal fructose absorption mediated by the facilitative glucose transporter glut5.
Fructose is found in foods containing sucrose fruits, high fructose corn syrups, and honey. The role of fructose in metabolism and cancer article pdf available in hormone molecular biology and clinical investigation may 2015 with 10,954 reads how we measure reads. Herman 1 1 division of endocrinology and metabolism and duke molecular physiology institute, duke university medical center, durham, north carolina, usa. On the basis of ug of wetweight the following results were found. Glyceraldehyde is then converted to glyceraldehyde3phosphate via triokinase.
Fructose is absorbed in the small intestine and metabolized in the liver where it stimulates fructolysis, glycolysis, lipogenesis, and glucose production. Despite the similarity in their structures, fructose and glucose are metabolized in different ways. Fructose seems to influence multiple metabolic pathways in the liver that results in enhanced lipogenesis, generation of uric acid, er stress, and inflammation. Fructose promotes complications in glucose metabolism, accumulation of triacylglycerol in the hepatocytes, and alterations in the lipid pro. These products comprise a large proportion of the modern diet, in particular in children, adolescents, and young adults. Metabolism of excess fructose, which is metabolized differently than glucose, is a general major disaster for human health. Besides these metabolic effects, fructose effects on mineral metabolism have also been considered. Apr 21, 2017 fructose enters glycolytic metabolism after phosphorylation by ketohexokinase khk and is converted to fructose1phosphate f1p. Fructose has indeed been reported to decrease copper absorption in rats 14. The primary disorder of fructose metabolism is hereditary fructose intolerance hfi. As maybe seen three organs share the specific route of fructose i contain glucose, fructose, and metabolism bywhichmorethan70%is utilized. Fructose metabolism and health risks omics international. The metabolism of food derived sucrose, fruit sugars, honey, and high fructose corn syrup, major sources of fructose and glucose in the diet, are currently under study, and the biological effects resulting from the use of experimentally formulated mixtures of glucose and fructose.
Consumption of fructose, the sweetest of all naturally occurring carbohydrates, has increased dramatically in the last 40 years and is today commonly used commercially in soft drinks, juice, and baked goods. The physiological functions of fructolytic intestinal and renal cellsremainlargelyputative. Consumption of fructose has been shown to be highly correlated with the development of diabetes, obesity and the metabolic syndrome. Fructose metabolism in key metabolic tissues including the small intestine, liver, and kidney may contribute to diverse cardiometabolic risk factors including steatosis, increased glucose production, hypertriglyceridemia, increased adiposity, and hypertension.
Fructosedriven glycolysis supports anoxia resistance in. Uric acid, a byproduct of uncontrolled fructose metabolism is known risk factor for hypertension. Fructose metabolism in humans what isotopic tracer. This is a rare autosomal recessive disorder triggered by ingestion of fructose, sucrose, or sorbitol, which may present clinically when infants are weaned from breast milk or formula and juice or fruit are added to the diet or when they receive a formula that. When it becomes pyruvate, it enters the tricarboxylic acid cycle and fatty acid synthesis figure 1 8. Fructose is a monosaccharide that is present in high concentrations in fruit and honey and is a constituent of sucrose and sorbitol.
For fructose to enter the pathways of intermediary metabolism, it must be. To place the metabolism of labeled sugars in context, it is helpful to briefly discuss what is known about the uptake of fructose, glucose and sucrose from the gut, interdependencies, and entry into the circulation. Fructose 6 phosphate fructose 1,6 bisphosphate regulation by f26bp. Fructose metabolism disorders msd manual professional edition. Identifying the etiology of diabetes is key to prevention. All three of these are only found in the liver and kidneys of rats and humans. Objective to assess the metabolic effects of chronic dietary fructose consumption in diabetic subjects. Finally, we discuss healthier alternatives to ssbs and strategies to reduce ssb intake. Increased understanding of fructose metabolism, which begins with uptake via the intestine, is important because fructose now constitutes a physiologically significant portion of human diets and is associated with increased incidence of certain cancers and metabolic diseases. Intestinal fructose and glucose metabolism in health and disease. Fructolysis refers to the metabolism of fructose from dietary sources.
Long chains of fructose are called fructans and are found in certain vegetables, wheat, and other foods. Fructose enters glycolytic metabolism after phosphorylation by ketohexokinase khk and is converted to fructose 1phosphate f1p. Fructose is an intermediary in the metabolism of glucose, but there is no biological need for dietary fructose. Fructose consumption in the development of obesity and the. This is the reason why excess fructose can cause obesity, thereby affecting type 2 diabetes. Although the metabolism of fructose and glucose share many of the same intermediate structures, they have very different metabolic fates in human metabolism. The problems with elevated uric acid levels, and what it tells us about how sugar causes disease 31. In this sense, the signaling properties of fructosederived f1p, and particularly its regulation of gck activity, may function as an evolved mechanism allowing the liver to use fructose metabolism to sense sugar i. Aldolase bmediated fructose metabolism drives metabolic. Fructose and simple sugars are a substantial part of the western diet, and their influence on human health remains controversial. Some people will feel better quickly while others need more. Fructose absorption and metabolism in the gut 26 b.
Pdf fructose metabolism and metabolic disease researchgate. The enzyme activities involved in fructose metabolism were measured in samples of human liver. Fructose metabolism and metabolic disease article pdf available in journal of clinical investigation 1282. Fructose metabolism in key metabolic tissues including the small intestine, liver, and kidney may contribute to diverse cardiometabolic risk factors. This may result in hypertriglyceridemia and fatty liver. Fructose metabolism is best understood by considering three enzymes. Three inborn errors are known in the pathway of fructose metabolism depicted in fig. Fructose metabolism the major natural sources of fructose in the human diet are fruits, honey, and sucrose a disaccharide of glucose and fructose. Fructose metabolism disorders pediatrics merck manuals. The utilization of fructose by other peripheral tissues seems to be negligible. Hepatic metabolism fructose can be found in equimolar amounts with glucose from sucrose.
Sucrose, highfructose corn syrup, and fructose, their. Metabolic disease disorders of carbohydrate metabolism. What is the difference between glucose and fructose metabolism. Metabolic, hedonic, and societal parallels with ethanol. In water solution, fructose exists as an equilibrium mixture of 70% fructopyranose and about 22% fructofuranose, as well as small amounts of three other forms, including the. Plasma concentration of fructose are increased only trivially after fructose intake in humans as first pass metabolism by liver covers about 8090% of the fructose load. Fructose was initially thought to be advisable for patients with diabetes due to its low glycemic index. In the liver, fructose is rapidly converted to fructose 1phosphate via fructokinase. Clinical studies in fructose nutrition have proven very difficult to conduct and interpret. Both controversy and confusion exist concerning fructose, sucrose, and high fructose corn syrup hfcs with respect to their metabolism and health effects. Crown,6 nikolai rakhilin,3,5 yiwei ai, 4lihua wang, 3rui xi, inna astapova,6,7 yan han, jiahe li, bradley b.
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