- # About the Author
- # About the web site
- # Our second web site
- # Question of the day
- A New Book of Biochemistry
- Acid Base Balance
- Animations Links
- Biochemical Techniques
- Biochemistry Quiz
- Biological Oxidation
- Chemistry of Carbohydrates
- Chemistry of Lipids and Eicosanoids
- Chemistry of Nucleotides
- Chemistry of Proteins
- Diabetes Mellitus
- Diet and Nutrition
- Facebook Group Posts
- Haem Synthesis and Degradation
- Hemoglobin and Hemoglobinopathies
- Liver Function Tests
- Metabolism – Carbohydrates
- Metabolism – Lipids
- Metabolism – Nucleotides
- Metabolism – Proteins
- Metabolism of Alcohol
- Molecular Biology
- Past Papers
- Power Point Presentations
- Practical Biochemistry
- Abnormal Urine
- Blood Glucose Estimation
- Blood Urea and Urea Clearance Estimation
- Normal Laboratory Reference Values
- Normal Urine Analysis
- Power point presentations
- Protein Precipitation Reactions
- Reactions of Carbohydrates
- Serum Creatinine and Creatinine clearance estimation
- Serum Total Protein estimation
- Practice Questions
- Quick revisions
- Renal Function Tests
- Semester Paper
- Students’ corner
- Water and Electrolyte balance and Imbalance
Subjective Questions- Fructose Metabolism (Solved)- Set-2
Answer- Fructose does not stimulate the release of insulin. The reduced insulin/glucagon ratio stimulates gluconeogenesis and inhibits glycolysis. That is, glucagon dominates the picture, increasing fructose bisphosphatase activity and leading to formation of glucose. Gluconeogenesis occurs only if fructose in pure form is consumed. However, the more usual situation is consumption of fructose as sugar as a sweetener in a “normal” meal. In other words, fructose is consumed together with starch or sugar. This leads to increases in blood sugar and insulin levels directly with a rapid cessation of gluconeogenesis.
Mechanism – Increased concentrations of DHAP (dihydroxy acetone phosphate)and glyceraldehyde 3-phosphate produced from the metabolism of fructose in the liver drive the pathway toward glucose and subsequent glycogen synthesis.
Dihydroxyacetone phosphate and Glyceraldehyde -3-P produced from fructose metabolism condense together in the presence of Aldolase to form Fructose 1,6 bisphosphate, that is cleaved by fructose 1,6 bisphosphatase to form fructose-6-P. Glucose-6-P is produced from Fructose-6-P by the action of Phospho hexose isomerase and free glucose is produced from glucose-6-p by the action of glucose-6-phosphatse. Hence by these reactions, Glucose is produced from fructose and contributes to blood sugar level.
Surplus glucose-6-p can enter the pentose phosphate pathway or it can be converted to Glucose-1-P under the effect of Phosphoglucomutase enzyme, which is subsequently used up for the formation of Glycogen. (Figure 7)
It appears that fructose is a better substrate for glycogen synthesis than glucose and that glycogen replenishment takes precedence over triglyceride formation. Once liver glycogen is replenished, the intermediates of fructose metabolism are primarily directed toward triglyceride synthesis.
Figure -7- showing effects of fructose metabolism on glycogen synthesis.
Q.6– What is Essential fructosuria?
Answer- Essential fructosuria, also known as hepatic fructokinase deficiency or keto hexokinase deficiency, is a hereditary metabolic disorder caused by a deficiency of hepatic fructokinase, leading to fructose being excreted in urine. The inheritance is autosomal recessive.
Essential fructosuria, apparently a harmless condition, is an extremely rare error of metabolism, the recognition of which is of importance because it may be mistaken for diabetes mellitus.It is characterized by the patient’s inability to utilize fructose normally, whether it is ingested as simple fructose or as a substance capable of yielding fructose on digestion, such as cane sugar. It is manifested clinically by a symptomless excretion of fructose in urine.
Essential fructosuria should not be confused with hereditary fructose intolerance which is a very serious condition, and is due to deficiency of Aldolase B enzyme. It causes a rise in uric acid, growth abnormalities, in severe cases hepatic or renal failure and finally coma or death.
On the other hand, being symptomless, fructosuria is commonly left undetected or undiagnosed.
Q.7– What is the reason that even after consuming a large amount of fructose rich drink, appetite is not suppressed?
Answer– Fructose does not stimulate release of insulin. One of insulin’s important functions is central regulation of hunger. Fructose does not affect the hypothalamus directly or through insulin. Fructose does not appear to dampen the sense of hunger.
Insulin release can modulate food intake by at least 2 mechanisms. First, insulin concentrations in the central nervous system have a direct inhibitory effect on food intake. In addition, insulin may modify food intake by its effect on leptin secretion, which is mainly regulated by insulin-induced changes in glucose metabolism in fat cells. Insulin increases leptin release with a time delay of several hours. Thus, a low insulin concentration after ingestion of fructose would be associated with lower average leptin concentrations than would be seen after ingestion of glucose. Because leptin inhibits food intake, the lower leptin concentrations induced by fructose would tend to enhance food intake and thus the appetite is not suppressed.
Q.8- What are the important differences between metabolism of glucose and fructose?
Answer- Fructose and Glucose differ from each other in their metabolism as follows-
1) Absorption –
The digestive and absorptive processes for glucose and fructose are different. When disaccharides such as sucrose or maltose enter the intestine, they are cleaved by disaccharidases. A sodium-glucose co transporter absorbs the glucose that is formed from cleavage of sucrose. Fructose, in contrast, is absorbed further down in the duodenum and jejunum by a non-sodium-dependent process. After absorption, glucose and fructose enter the portal circulation and either is transported to the liver, where fructose can be taken up and converted to glucose, or passes into the general circulation.
2) Insulin release
Along with 2 peptides, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 released from the gastrointestinal tract, circulating glucose increases insulin release from the pancreas. Fructose does not stimulate insulin secretion, probably because the ß cells of the pancreas lack the fructose transporter Glut-5.
3) Fructose metabolism
The metabolism of fructose differs from that of glucose in several other ways as well; Glucose enters cells by a transport mechanism (Glut-4) that is insulin dependent in most tissues (Adipose tissues and skeletal muscles). Insulin activates the insulin receptor, which in turn increases the density of glucose transporters on the cell surface and thus facilitates the entry of glucose. Once inside the cell,glucose is phosphorylated by glucokinase/hexokinase to become glucose-6- phosphate, from which the intracellular metabolism of glucose begins. Intracellular enzymes can tightly control conversion of glucose-6-phosphate to the glycerol backbone of triacylglycerols through modulation by phosphofructokinase.
In contrast with glucose, fructose enters cells via a Glut-5 transporter that does not depend on insulin. This transporter is absent from pancreatic ß cells and the brain, which indicates limited entry of fructose into these tissues. Glucose provides “satiety” signals to the brain that fructose cannot provide because it is not transported into the brain. Once inside the cell, fructose is phosphorylated to form fructose-1-phosphate. In this configuration, fructose is readily cleaved by aldolase to form trioses that are the backbone for phospholipid and Triacylglycerol synthesis. Fructose also provides carbon atoms for synthesis of long-chain fatty acids, although in humans, the quantity of these carbon atoms is small. Thus, fructose facilitates the biochemical formation of triacylglycerols more efficiently than does glucose.
Q.9-Why is it said that, ‘Fructose is not a direct energy source for muscles and the brain’?
Answer- These tissues rely on the hexokinase catalyzed phosphorylation of glucose for energy metabolism. They do not take up fructose from the circulation since they lack both fructokinase and GLUT2. Fructose does increase hepatic fatty acid production and serum lipids and these can be utilized in muscle. However, dyslipidemia is not a desirable situation.
Q.10- Fructose has often been suggested as a treatment for hypoglycemia. There are several good reasons to discourage this. Briefly explain the reasons.
Answer- Firstly the formation of glucose from Fructose is not an immediate process and
Figure 8- showing the fructose metabolism and energy expenditure
Secondly the conversion of fructose to glucose uses 2 ATPs. One ATP is spent at the first step for the formation of fructose-1-P and the second ATP is spent for the conversion of Glyceraldehyde to Glyceraldehyde-3-p (Figure 8).Normal hepatic activity alone utilizes all of the liver’s ATP-synthesizing capacity. There is no good reason to increase hepatic ATP utilization. Glucose metabolism on the other hand produces ATP instead of utilizing.
Moreover fructose is not a direct energy source for brain and muscle as these tissue lack fructokinase and fructose transporters while Glucose is a preferred fuel for brain and can be utilized in almost all the calls of the body. Hence Glucose (also called dextrose) instead of fructose can be given orally or intravenously depending upon the situation to treat hypoglycemia.
Q-11 -Parenteral feeding with solutions containing fructose can result in blood fructose concentrations that are several times higher than can be achieved with an oral load. What is the reason for this?
Answer- Since the rate of entry into the hepatocyte is dependent on the fructose gradient across the cell, intravenous loading results in initial increased entry into the liver and increased formation of F1P. Since the rate of formation of F1P is much faster than its further metabolism,the accumulated fructose-1P, restricts further flow of fructose in to the cells with the resultant increase in the circulating fructose load.
The toxic effects of F1P can also be exhibited in the form of hyperuricemia and hyperuricosuria by the mechanisms described separately.
Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!