Why can't cells directly absorb glucose?

Fructose - uptake into the cell, breakdown and biosynthesis

Table of Contents

Image: “Intestinal monosaccharide transporters” from NuFS, San Jose State University. License: CC BY-SA 3.0

Chemical properties of fructose

Fructose (formerly also laevulose for "counterclockwise") with the sum formula C6H12O6 belongs to the hexoses, the sugars with 6 carbon atoms. It also has a keto group, defined as a carbon atom with a double bond to an oxygen atom. Therefore, fructose is also a ketosis. Since the molecule is optically active, it occurs in two mirror-image isomers, the so-called enantiomers. These are mostly in theFischer projection pictured. This is an open-chain representation to illustrate the spatial structure of chiral compounds.

The stereo descriptor D stands for Dexter (Latin for right), since the horizontal remainder with the higher priority, i.e. the lowest OH in the Fischer projection, points to the right. The opposite is true for the L, for laevus (Latin for left). The enantiomer L-fructose is physiologically irrelevant.

There is also the Haworth notationwhere the molecule is drawn as a flat ring. Fructose is a specialty because it is present in crystalline form as a six-membered ring (so-called fructopyranose) and in bound form as a five-membered ring (so-called fructofuranose). The α- and β-anomers of the respective ring forms can be converted into one another in aqueous solution and are in equilibrium with one another.

Occurrence of fructose in foods

Fructose (from Latin fructis: fruit) occurs naturally as a monosaccharide, i.e. simple sugar, mainly in pome fruit (for example 6g fructose per 100g apple) and honey (40g per 100g). However, we take most of the fructose in the form of the disaccharide Sucrose (from Latin saccharum: sugar) our colloquial household sugar. Sucrose is a molecule made up of α-D-glucose and β-fructose, which are linked via an α, β-1,2-glycosidic bond.

Increasingly, industrially produced foods from corn contain fructose in the form of high-fructose-corn syrup, in Germany as Glucose-fructose syrup declared. Due to its very sweet taste and its good solubility in water, it is mainly used to sweeten soft drinks.

Uptake of fructose in the cell

in the upper small intestine sucrose is first split into glucose and fructose by the enzyme sucrose. The absorption of fructose from the intestinal lumen of the small intestine into the enterocytes (Latin for intestinal cells) takes place in contrast to glucose passive, so independent of energy. The Fructose transporterGLUT5 (to a lesser extent other class II sugar transporters such as GLUT7, 9 and 11) transport fructose along its concentration gradient into the cell interior.

Accordingly, when an equilibrium has been reached between intra- and extracellular, fructose is no longer absorbed and is therefore never completely absorbed. This means that fructose is osmotically effective in the intestine if it is very high in food and can lead to diarrhea, especially in small children.

Image: “Intestinal monosaccharide transporters” from NuFS, San Jose State University. License: CC BY-SA 3.0

Fructose passes through the basolateral cell membrane of the intestinal cells, i.e. the one facing the bloodstream, mainly with the help of the GLUT2 transporters. This transport protein also transports glucose and galactose into the blood. The blood flow from the small intestine to the liver then takes place via the portal vein.

Fructose breakdown in the liver cells

Because the fructose uptake into the cells insulin independent is, fructose has long been used as a sweetener in so-called diet products for diabetics. However, such products have not been available since 2010.

  • D-fructose is made in the cells of the liver, the hepatocytes, by the enzyme Fructokinase (also called ketohexokinase) in D-fructose-1-phosphat converted, it can no longer leave the cell. This reaction is ATP-dependent.
  • Fructose-1-phosphate is made by Aldolase B in Dihydroxyacetone phosphate and Glyceraldehydesplit. Dihydroxyacetone phosphate is an intermediate product of glycolysis and is further metabolized to produce energy.
  • Glyceraldehyde is produced by the Triose kinase ATP dependent too Glyceraldehyde-3-phosphate phosphorylated and can thus enter glycolysis or triglyceride synthesis and be deposited as depot fat.

The essential fructosemia and fructosuria

The essential fructosemia and fructosuria is a defect of the Fructokinase of the hepatocytes. This enzyme failure leads to an accumulation of fructose in the blood (fructosemia) and in the urine (fructosuria). This rare condition has no pathological value and is therefore not in need of treatment. The patients have no symptoms and the essential fructosemia or uria is in most cases a chance diagnosis.

Hereditary fructose intolerance

The incidence of these rare, autosomal recessive inherited disease is 1: 20,000 to 1: 130,000 depending on the source. Causal is a malfunction of the enzyme Aldolase Bwhich normally cleaves fructose-1-phosphate in the hepatocytes to dihydroxyacetene phosphate and glyceraldehyde. Aldolase A, an enzyme in glycolysis, is not affected by this defect. However, aldolase A metabolizes fructose-1-phosphate 50 times more slowly than its actual substrate fructose-1,6-bisphosphate.

This leads to a Accumulation of fructose-1-phosphate in the hepatocytes. There it inhibits glycolysis and gluconeogenesis enzymes such as fructose-1,6-bisphosphatase and glycogen phosphorylase. This is what happens in times of hunger life-threatening hypoglycaemia, since no glucose can be synthesized from glycogen. In addition, a Hepatomegaly with progressive destruction of the liver up to cirrhosis of the liver.

The first symptoms usually appear when you start feeding baby porridge containing fruit, as breast milk is fructose-free. With mild forms, the child often has an aversion to fruit juices and other foods containing fructose, thrives poorly, and cries a lot. In severe cases, the infants become hypoglycemic, with symptoms of the adrenergic counter-reaction such as sweating, tremors, vomiting, seizures and even coma. Since aldolase B is also present in the kidneys, hereditary fructose intolerance also leads to Kidney damage with proteinuria (the increased excretion of proteins in the urine).

The diagnosis is carried out with molecular genetic testswhich cover the 3 most common mutations (A149P, A174D and N334K) of aldose B. One of these three mutations can be detected in 90% of those affected. Newborn screening does not capture hereditary fructose intolerance.

As with most congenital metabolic disorders, the only effective therapy is to avoid foods containing fructose altogether. Vitamins contained in fruits and vegetables should be supplied to young children. As Course parameters serves the partial thromboplastin time (PTT) and antithrombin III, as these coagulation parameters or factors are pathological even with little liver damage.

Special care should be taken with Sorbitol Infusions commanded. Due to their osmotic effectiveness, these are rarely used to lower intracranial pressure. Sorbitol cannot be broken down in hereditary fructose intolerance either and can lead to the same symptoms and even death.

The intestinal fructose intolerance

Intestinal fructose intolerance is much more common than hereditary fructose intolerance. About 1/3 of the people suffers from one Fructose malabsorptionwhich means that only a small amount of fructose is absorbed in the small intestine and so a significant part of it ends up in the large intestine. In the large intestine, fructose increases the osmotic pressure and thus removes fluid from the intestine.

In addition, the bacteria of the colon flora ferment the fructose into carbon dioxide, short-chain fatty acids and methane. This can cause it to Diarrhea and meteorism come and one then speaks of intestinal fructose intolerance. In turn, about 1/3 of people with fructose malabsorption suffer from this.

The causes of fructose malabsorption are many, for example one below average number or performance of GLUT5 may be the cause, but also a rapid passage of the chyme through the small intestine. It is entirely possible that fructose intolerance is much more like lactose intolerance Standard variantwhen it is a disease.

Secondarily, intestinal fructose intolerance can also arise from a chronic inflammatory bowel disease that affects the small intestine. In Crohn's disease, for example, the mucous membrane of the small intestine is so severely destroyed that fructose can no longer be absorbed. As with hereditary fructose tolerance, the only effective therapy consists of Avoid fructose, Sorbitol and other oligo- (mannitol, xylitol) or dissaccharides, as these too often trigger the same symptoms.

The reason why most fructose intolerants can still tolerate sucrose is due to the GLUT2 transport protein. GLUT2 is also located in the apical membrane of the small intestine cells and is quickly incorporated into the cell membrane when the transport protein SGLT1, an ATP-dependent sodium-glucose cotransporter, transports glucose. GLUT2 then channels both glucose and fructose into the enterocytes independently of GLUT5. The German Nutrition Society therefore does not recommend a diet without fruit and fructose-containing vegetables, but rather fruits that contain roughly equal proportions of glucose and fructose.

Fructosemia / uriaHereditary fructose intoleranceIntestinal fructose intolerance
frequencyUnknown, as it is often a chance diagnosis1 : 20.000 – 1 : 130.000about 10% of the population
malfunctionFructokinaseAldolase BGLUT5
SymptomsNoHypoglycaemia, liver fibrosis / cirrhosis, kidney damageMeteorism, flatulence, diarrhea
therapyUnnecessaryStrict diet without fructoseLow fructose diet

Fructose biosynthesis from glucose

About the so-called Polyol route is a biosynthesis of fructose from glucose im extrahepatic tissue possible. This takes place in particular in a testosterone-dependent manner in the glandulae vesiculosae, the Seminal vesicles, the man. A high proportion of fructose is then contained in the semen and serves as a nutrient for the sperm in the ejaculate. The fructose content of the fresh ejaculate is determined with the fructolysis test. If the level is reduced, this indicates an underfunction of the testosterone-producing Leydig cells in the testes.

  • The Aldose reductasefirst reduces the aldehyde group on carbon atom 1 of the glucose to a -CH2OH group. The resulting connection is called Sorbitol (or sorbitol for short).
  • After that, sorbitol on carbon atom 2 is replaced by the Sorbitol dehydrogenase oxidizes, it arises Fructose.

For aldolase reductase, NADPH serves as a cosubstrate, which oxidizes to NADP. In the second step, NAD + is reduced to NADH by sorbitol dehydrogenase. In net terms, this leads to a conversion of NADPH to NADH, which is held responsible for the long-term consequences of permanently high blood sugar levels. This is due to the fact that NADPH Has an antioxidant effect and the body lacks a substrate.
In addition, in diabetes mellitus, an increased fructose concentration in the lens of the eye can lead to the formation of a Cataractlead to cataracts. Sorbitol and glucose have a strong osmotic effect and cause the lens of the eye to swell.

Fructose as a disease trigger

Several studies, including a study by the German Institute for Nutritional Research, show a connection between increased fructose intake and Obesity. Fructose not only increases that Lipogenesisbut also leads to one increased feeling of hunger, because no insulin is released, which is also a satiety hormone.

In addition, a high-fructose diet leads to a Increase in plasma lipids and to Insulin resistance. So fructose has a permanent diabetogenic effect and that more than glucose. So overall, fructose increases the incidence of one metabolic syndromewhich is defined as the coexistence of obesity, dyslipoproteinemia, impaired glucose tolerance and arterial hypertension.

Other research shows a connection between fructose intake and non-alcoholic fatty liver (steatosis hepatis) on, which is a precursor to cirrhosis of the liver.
Also the risk for gout is greatly increased by soft drinks sweetened with fructose, as prospective studies with several thousand patients show. The cause is the consumption of ATP in the breakdown of fructose. IMP is produced, which increases the concentration of uric acid via the breakdown of purines.

According to the latest studies, even the risk of cancer such as the Pancreatic carcinoma through a fructose-heavy diet. Fructose contributes to the synthesis of nucleic acids, which promotes the proliferation of cancer cells.

For these reasons, the Food and Agriculture Organization of the United States recommends reducing the daily intake of free sugars such as fructose to less than 10% of the total amount of energy.

Popular exam questions about fructose

The solutions can be found below the references.

1. The uptake of fructose in the cells of the small intestine takes place ...

  1. ... about a sodium symport.
  2. ... depending on insulin via the transport protein GLUT2.
  3. ... along the concentration gradient via the transport protein GLUT5.
  4. ... energy-dependent via a sodium-potassium-ATPase.
  5. ... only in the form of sucrose via the transport protein GLUT2.

2. In the fructolysis test, does a reduced initial level of fructose in the ejaculate indicate a malfunction in which cells?

  1. Leydig cells
  2. Sertoli cells
  3. Prostate cells
  4. Epididymal cells
  5. Spermatocytes I

3. What does not apply to hereditary fructose intolerance?

  1. It is inherited as an autosomal recessive trait.
  2. The cause is a defect in aldolase B.
  3. Life-threatening hypoglycaemia can occur during periods of fasting.
  4. The infants should not be breast-fed as galactose causes the same symptoms.
  5. Affected people may have hepatomegaly at diagnosis.


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Solutions to the exam questions: 1C, 2A, 3D

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