Question 1: What are the two ways fructose exists in food?
Answer: Fructose exists in food as a monosaccharide (free fructose) or as a unit of a disaccharide (sucrose).
Question 2: What is the name of the transporter protein responsible for fructose absorption in the intestine?
Answer: Fructose absorption in the intestine occurs via facilitated transport involving GLUT5 transport proteins.
Question 3: Why is the rate of fructose metabolism faster than glucose metabolism?
Answer: Fructose metabolism is faster because it bypasses the key regulatory enzyme phosphofructokinase-1 (PFK-1) in glycolysis. Fructose is directly phosphorylated by fructokinase to fructose-1-phosphate, which is cleaved by aldolase B into dihydroxyacetone phosphate (DHAP) and glyceraldehyde, intermediates that enter glycolysis downstream of PFK-1.
Question 4: What is the biochemical basis of hereditary fructose intolerance?
Answer: Hereditary fructose intolerance is caused by a deficiency in the aldolase B enzyme. This deficiency prevents the breakdown of fructose-1-phosphate, leading to its accumulation in the liver and other organs.
Question 5: List three long-term consequences of excessive fructose exposure.
Answer: Three long-term consequences of excessive fructose exposure are liver failure, renal tubulopathy, and hyperuricemia.
Question 6: What is the difference between essential fructosuria and hereditary fructose intolerance?
Answer: Essential fructosuria is a deficiency of hepatic fructokinase, which leads to fructose being excreted in the urine. It is generally asymptomatic. Hereditary fructose intolerance is a deficiency of aldolase B, which leads to the accumulation of fructose-1-phosphate. It causes a range of symptoms, including vomiting, abdominal pain, and hypoglycemia.
Question 7: What is the primary dietary source of galactose?
Answer: The primary dietary source of galactose is lactose, which is found in milk and milk products.
Question 8: Name three important compounds that utilize UDP-galactose in their formation.
Answer: Three important compounds that utilize UDP-galactose in their formation are lactose, glycolipids (cerebrosides), and glycoproteins.
Question 9: What advice can be given to a lactose-intolerant pregnant woman regarding breastfeeding?
Answer: A lactose-intolerant pregnant woman can still breastfeed her baby. Lactose is synthesized from UDP galactose and glucose, and galactose can be synthesized from glucose if it is not present in the diet.
Question 10: List five clinical features associated with galactosemia.
Answer: Five clinical features associated with galactosemia include failure of neonates to thrive, vomiting and diarrhea following the ingestion of milk, impaired liver function, cataracts, and mental retardation in untreated cases.
Question 11: Besides the liver, which other organs are involved in fructose metabolism?
Answer: Fructose metabolism primarily occurs in the liver; however, fructokinase is also present in the kidneys and small intestine.
Question 12: In which tissues is the sorbitol pathway active, and what is its significance?
Answer: The sorbitol pathway is active in tissues like seminal vesicles, the liver, sperm, and ovaries. This pathway is significant because it generates free fructose in seminal plasma, which serves as the primary energy source for sperm motility.
Question 13: How does hyperglycemia impact the sorbitol pathway, and what are the potential consequences?
Answer: In hyperglycemic conditions, the excess glucose gets converted to sorbitol via the sorbitol pathway. Since the enzyme sorbitol dehydrogenase is deficient in tissues like the lens, nerves, and kidneys, sorbitol accumulates, leading to complications such as cataracts, neuropathies, and nephropathies.
Question 14: How does the affinity of hexokinase for glucose and fructose affect fructose metabolism? Answer: Hexokinase has a 20 times greater affinity for glucose than fructose. Consequently, only a negligible amount of fructose is phosphorylated by hexokinase unless fructose concentrations within the cell become unusually high.
Question 15: What is the mechanism behind hyperuricemia resulting from excessive fructose ingestion?
Answer: Excessive fructose intake depletes the inorganic phosphate pool, leading to the loss of inhibition on AMP deaminase. This results in increased uric acid production and hyperuricemia.
Question 16: Apart from lactose, what other sources contribute to galactose in the body?
Answer: Besides lactose from dietary sources, galactose can also be obtained through the breakdown of galactolipids and glycoproteins.
Question 17: Describe the role of UDP-galactose in lactose synthesis.
Answer: UDP-galactose provides the galactose moiety required for lactose synthesis. The enzyme lactose synthase, present in the endoplasmic reticulum of lactating mammary glands, catalyzes the transfer of galactose from UDP-galactose to glucose, forming lactose.
Question 18: What are the three enzyme deficiencies associated with galactosemia, and what are their clinical consequences?
Answer: Galactosemia can arise from deficiencies in three enzymes:
○ Galactose-1-phosphate uridyl transferase (GALT) deficiency, the most common type, leads to classical galactosemia, characterized by symptoms such as vomiting, diarrhea, liver dysfunction, and mental retardation.
○ Galactokinase deficiency results in a milder form of galactosemia.
○ UDP-galactose-4-epimerase deficiency is the rarest form of galactosemia.
Question 19: Explain why individuals with hereditary fructose intolerance (HFI) develop hypoglycemia after consuming fructose-containing foods.
Answer: In HFI, a deficiency in aldolase B leads to the accumulation of fructose-1-phosphate, which traps inorganic phosphate (Pi) and reduces its availability for ATP synthesis. This inhibits gluconeogenesis and glycogenolysis, causing hypoglycemia after fructose ingestion.
Question 20: How does a deficiency in galactose-1-phosphate uridyltransferase (GALT) lead to the symptoms of classic galactosemia?
Answer: A GALT deficiency results in the accumulation of galactose-1-phosphate and galactitol. These intermediates are toxic and damage tissues. Galactitol accumulates in the lens, causing cataracts, while galactose-1-phosphate disrupts liver and kidney function, leading to hepatomegaly, jaundice, and renal tubular dysfunction.
Question 21: Why does fructokinase deficiency result in benign fructosuria, whereas aldolase B deficiency causes severe symptoms?
Answer: Fructokinase deficiency leads to benign fructosuria because fructose cannot be efficiently phosphorylated and is excreted in the urine, with no toxic intermediates accumulating. Moreover, fructose can also be alternatively phosphorylated by Hexokinase. In contrast, aldolase B deficiency causes the accumulation of fructose-1-phosphate, which depletes Pi and ATP, leading to severe metabolic disturbances like hypoglycemia and liver dysfunction.
Question 22: How does the deficiency of aldose reductase impact the metabolism of galactose in galactosemia?
Answer: Aldose reductase converts galactose to galactitol in the polyol pathway. In galactosemia, aldose reductase deficiency would limit the accumulation of galactitol, reducing osmotic stress in tissues like the lens. However, it does not address the toxic effects of accumulated galactose-1-phosphate caused by other enzyme deficiencies like GALT.
Question 23: Why is the liver the primary site for fructose metabolism, and how does this differ from glucose metabolism?
Answer: The liver is the primary site for fructose metabolism because it expresses high levels of fructokinase and aldolase B, enzymes specific to the fructose metabolic pathway. In contrast, glucose metabolism occurs in almost all tissues due to the widespread presence of hexokinase and glycolytic enzymes. Fructose metabolism bypasses the key regulatory step catalyzed by phosphofructokinase-1 (PFK-1) in glycolysis.
Question 24: Explain why infants with galactosemia are at risk of developing cataracts early in life.
Answer: In galactosemia, a deficiency in enzymes like GALT leads to the accumulation of galactose, which is converted to galactitol by aldose reductase. Galactitol accumulates in the lens of the eye, causing osmotic stress and crystallin protein aggregation, leading to the formation of cataracts.
Question 25: How does the accumulation of fructose-1-phosphate in hereditary fructose intolerance affect cellular energy metabolism?
Answer: Fructose-1-phosphate accumulation in hereditary fructose intolerance sequesters inorganic phosphate (Pi), reducing its availability for ATP synthesis. This leads to energy depletion, inhibits gluconeogenesis and glycogenolysis, and results in hypoglycemia and metabolic derangements.
Question 26: What is the significance of UDP-galactose in galactose metabolism, and how is it connected to glucose metabolism?
Answer: UDP-galactose is crucial for the interconversion of galactose and glucose. Through the enzyme UDP-galactose-4-epimerase, UDP-galactose is converted to UDP-glucose, which can enter glycolysis or glycogenesis. This interconversion ensures that galactose can be utilized in energy metabolism and for the synthesis of glycoproteins and glycolipids.