1. An exclusively breast-fed infant presents with vomiting, weight loss, jaundice, hepatomegaly, and bilateral cataracts. Which condition is most likely responsible for these symptoms?
A. Breast milk jaundice
B. Classical Galactosemia
C. Hereditary fructose intolerance
D. Type 1 Diabetes mellitus
E. Von Gierke’s disease
Correct Answer: B. Classical Galactosemia
Explanation: Classical galactosemia is a rare metabolic disorder caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT). This enzyme deficiency leads to the accumulation of toxic metabolites such as galactitol and galactose-1-phosphate when galactose is ingested. Symptoms typically appear after the infant begins consuming breast milk or formula containing lactose (a source of galactose). Key features include vomiting, weight loss, jaundice, hepatomegaly, and bilateral cataracts. Early diagnosis and the elimination of galactose from the diet are critical to prevent severe complications like liver failure, sepsis, and developmental delays.
Incorrect options
A. Breast milk jaundice
• Explanation: Breast milk jaundice is a benign condition characterized by prolonged unconjugated hyperbilirubinemia in otherwise healthy breastfed infants. It is not associated with hepatomegaly, vomiting, cataracts, or weight loss. It is caused by substances in breast milk that may inhibit the conjugation of bilirubin, but it does not lead to the severe metabolic and systemic symptoms described.
C. Hereditary fructose intolerance
• Explanation: This disorder is caused by a deficiency of aldolase B, leading to an inability to metabolize fructose-1-phosphate. Symptoms typically manifest after introducing fructose-containing foods (e.g., fruits, sucrose, or honey) and are not present exclusively in breast-fed infants. Symptoms include vomiting, hypoglycemia, hepatomegaly, and failure to thrive, but cataracts are not a feature.
D. Type 1 Diabetes mellitus
• Explanation: Type 1 diabetes mellitus is an autoimmune condition leading to insulin deficiency and hyperglycemia. It typically presents in older children or adolescents and is associated with symptoms like polyuria, polydipsia, and weight loss. It does not cause cataracts, jaundice, or hepatomegaly in neonates.
E. Von Gierke’s disease
• Explanation: Von Gierke’s disease (glycogen storage disease type I) is a metabolic disorder caused by glucose-6-phosphatase deficiency. It leads to severe fasting hypoglycemia, hepatomegaly, lactic acidosis, and hyperlipidemia. While jaundice and hepatomegaly may be present, cataracts and vomiting are not typical features.
2. A nutritionist explains to a patient with digestive issues the various mechanisms through which different sugars are absorbed in the intestines. Regarding fructose, the nutritionist mentions a specific mode of uptake on the mucosal membrane. How is fructose primarily absorbed?
A. Active transport
B. Combination of active transport and facilitated diffusion
C. Combination of active transport and passive diffusion
D. Facilitated diffusion
E. Passive diffusion
Correct Answer: D. Facilitated diffusion
• Explanation: Fructose is primarily absorbed in the intestines through facilitated diffusion. This process is mediated by the GLUT5 transporter on the apical (mucosal) membrane of enterocytes. Facilitated diffusion does not require energy, as fructose moves down its concentration gradient. Once inside the enterocyte, fructose is transported across the basolateral membrane into the bloodstream via the GLUT2 transporter.
Incorrect options
A. Active transport
• Explanation: Active transport requires energy, typically in the form of ATP, and is used for substances transported against their concentration gradient. Glucose and galactose are absorbed through secondary active transport using the sodium-glucose co-transporter (SGLT1), but this mechanism does not apply to fructose.
B. Combination of active transport and facilitated diffusion
• Explanation: This option does not apply to fructose absorption, as active transport is not involved. Fructose absorption relies exclusively on facilitated diffusion via GLUT5.
C. Combination of active transport and passive diffusion
• Explanation: This mechanism is incorrect for fructose absorption. Passive diffusion involves the movement of molecules directly across the membrane without the aid of a transporter, and fructose specifically requires GLUT5 for facilitated diffusion.
E. Passive diffusion
• Explanation: Passive diffusion involves the movement of substances across the cell membrane without a transporter and down their concentration gradient. Fructose absorption does not occur via this mechanism because it requires a specific transporter (GLUT5) for facilitated diffusion.
3. A reproductive endocrinologist was counseling a couple facing fertility challenges. The husband’s semen analysis indicated normal sperm count but reduced motility. Intrigued by this, the doctor ordered a metabolic profile of the seminal fluid. The results showed an unusually high concentration of an osmolyte compound, hinting at a possible enzymatic deficiency that prevents this compound’s conversion to fructose. Which enzyme is most likely deficient in this context?
A. Aldolase
B. Aldose reductase
C. Fructokinase
D. Hexokinase
E. Sorbitol dehydrogenase
Correct Answer: E. Sorbitol dehydrogenase
• Explanation: Sorbitol dehydrogenase is the enzyme responsible for converting sorbitol to fructose in the seminal vesicles. Fructose is an important energy source for sperm motility. A deficiency in sorbitol dehydrogenase results in the accumulation of sorbitol in seminal fluid, leading to reduced fructose availability and consequently impaired sperm motility. This aligns with the observed high concentration of the osmolyte (sorbitol) and reduced motility in the patient’s sperm.
Incorrect options
A. Aldolase
• Explanation: Aldolase is involved in the glycolytic pathway, converting fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. It is not directly involved in the conversion of sorbitol to fructose, making it an unlikely cause in this scenario.
B. Aldose reductase
• Explanation: Aldose reductase catalyzes the reduction of glucose to sorbitol, which is the first step in the polyol pathway. While its deficiency would prevent sorbitol formation, the case describes an accumulation of sorbitol, ruling out this enzyme as the cause.
C. Fructokinase
• Explanation: Fructokinase catalyzes the phosphorylation of fructose to fructose-1-phosphate in the liver and is not involved in the seminal conversion of sorbitol to fructose. A deficiency in this enzyme would lead to fructosuria rather than the symptoms described.
D. Hexokinase
• Explanation: Hexokinase phosphorylates glucose to glucose-6-phosphate as part of glycolysis. It is unrelated to the metabolism of sorbitol and fructose in the seminal pathway, making it an incorrect choice.
4. A 2-month-old infant was brought to the pediatrician by her parents due to poor feeding, vomiting, and jaundice. They reported that these symptoms began shortly after they started her on a regular formula feed. Blood tests and a metabolic profile were ordered. The results indicated a significant buildup of a specific compound. Given the infant’s presentation and history, which compound is most likely accumulating at toxic levels due to Classical Galactosemia?
A. Galactose-1-P
B. Glucose 6-P
C. Glucose-1-P
D. UDP Galactose
E. UDP Glucose
Correct Answer: A. Galactose-1-P
• Explanation: In Classical Galactosemia, there is a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT). This leads to the accumulation of galactose-1-phosphate (Galactose-1-P) in tissues, causing toxic effects in the liver, kidneys, and brain. The symptoms of poor feeding, vomiting, jaundice, and hepatomegaly are characteristic of this condition. Early detection and the elimination of dietary galactose (from lactose) are crucial for preventing long-term complications.
Incorrect options
B. Glucose 6-P
• Explanation: Glucose-6-phosphate is a key intermediate in glycolysis and gluconeogenesis but is not directly related to the galactose metabolism pathway. Its accumulation is seen in conditions like Von Gierke’s disease (glycogen storage disease type I), which presents differently with severe fasting hypoglycemia and lactic acidosis.
C. Glucose-1-P
• Explanation: Glucose-1-phosphate is a precursor for glycogen synthesis and is not the primary metabolite accumulating in Classical Galactosemia. Its buildup is not linked to the symptoms described in this case.
D. UDP Galactose
• Explanation: UDP-galactose is an intermediate in the conversion of galactose-1-phosphate to UDP-glucose. While UDP-galactose levels may be affected, the toxic metabolite responsible for the clinical symptoms in Classical Galactosemia is galactose-1-phosphate.
E. UDP Glucose
• Explanation: UDP-glucose is another intermediate in carbohydrate metabolism and is not the compound accumulating at toxic levels in Classical Galactosemia. Its metabolism is not directly impaired in this condition.
5. A 12-year-old boy, John, was brought to a metabolic specialist by his parents due to concerns about a potential hereditary metabolic disorder. They explained that several family members were diagnosed with familial fructokinase deficiency. However, those relatives seemed asymptomatic throughout their lives, and John himself didn’t display any overt symptoms despite the genetic predisposition. The metabolic specialist was not surprised and explained that there’s a specific reason why familial fructokinase deficiency typically doesn’t manifest with symptoms. What is that reason?
A. Excess fructose escapes into urine
B. Excess fructose is excreted through feces
C. Hexokinase can phosphorylate fructose
D. Liver Aldolase can metabolize it
E. Liver Glucokinase can phosphorylate fructose
Correct Answer: C. Hexokinase can phosphorylate fructose
• Explanation: In familial fructokinase deficiency (essential fructosuria), there is a deficiency in fructokinase, which normally converts fructose to fructose-1-phosphate in the liver. However, this condition is benign because hexokinase, an enzyme found in various tissues, can compensate by phosphorylating fructose to fructose-6-phosphate. This alternative pathway prevents fructose from accumulating in the blood to toxic levels, explaining the lack of symptoms in affected individuals.
Incorrect options
A. Excess fructose escapes into urine
• Explanation: In familial fructokinase deficiency (essential fructosuria), excess fructose that is not metabolized due to the lack of fructokinase escapes into the urine. While this is a characteristic feature of the condition, it is not harmful and does not contribute to any clinical symptoms. This benign excretion of fructose explains why individuals with essential fructosuria remain asymptomatic. However, the lack of symptoms is primarily due to compensation by hexokinase, which metabolizes fructose via an alternative pathway, making Option C the most precise answer.
B. Excess fructose is excreted through feces
• Explanation: Excess fructose is not typically excreted through feces in essential fructosuria. Fructose absorption occurs in the intestine, and any unphosphorylated fructose may escape into the urine rather than being excreted in feces.
D. Liver Aldolase can metabolize it
• Explanation: Aldolase B in the liver metabolizes fructose-1-phosphate, a product of fructokinase activity. However, in essential fructosuria, the deficiency of fructokinase prevents fructose from being converted to fructose-1-phosphate, so Aldolase B is not involved.
E. Liver Glucokinase can phosphorylate fructose
• Explanation: Glucokinase specifically phosphorylates glucose, not fructose. It plays no role in compensating for the deficiency of fructokinase in essential fructosuria.
6. Dr. Emily, a pediatric geneticist, was consulted for a 3-month-old baby girl named Mia. Mia’s parents reported that she had difficulty feeding and exhibited symptoms of jaundice. Initial blood tests showed elevated levels of galactose. Dr. suspected an enzyme deficiency early in the metabolic pathway of galactose. Which enzyme is responsible for this conversion?
A. Aldolase
B. Epimerase
C. Galactokinase
D. Galactose-1-P uridyl transferase
E. Hexokinase
Correct Answer: C. Galactokinase
• Explanation: Galactokinase is the enzyme responsible for the phosphorylation of galactose to galactose-1-phosphate in the first step of galactose metabolism. This phosphorylation traps galactose within the cell and prepares it for subsequent conversion to UDP-galactose by galactose-1-phosphate uridyltransferase. A deficiency in galactokinase can lead to galactosemia and an accumulation of galactitol, which is associated with cataracts but typically causes milder symptoms compared to deficiencies in other enzymes in the pathway.
Incorrect options:
A. Aldolase
• Explanation: Aldolase catalyzes a reaction in glycolysis and fructose metabolism, but it is not involved in the phosphorylation of galactose. It is irrelevant in this context.
B. Epimerase
• Explanation: UDP-galactose-4-epimerase converts UDP-galactose to UDP-glucose in the final step of the galactose metabolism pathway. This enzyme works downstream of the initial phosphorylation step and is not responsible for the conversion of galactose to galactose-1-phosphate.
D. Galactose-1-P uridyl transferase
• Explanation: Galactose-1-phosphate uridyltransferase (GALT) catalyzes the conversion of galactose-1-phosphate to UDP-galactose in the second step of galactose metabolism. Deficiency in this enzyme causes Classical Galactosemia, which leads to severe symptoms. However, this is not the enzyme responsible for the initial phosphorylation of galactose.
E. Hexokinase
• Explanation: Hexokinase phosphorylates glucose to glucose-6-phosphate and has minimal activity toward galactose. It does not play a significant role in galactose metabolism.
7. A 2-week-old infant is brought to the emergency department. Her metabolic screening indicates elevated galactose-1-phosphate levels, confirming a diagnosis of galactosemia. Which of the following manifestations is unlikely to be seen in this patient?
A. Cataracts
B. Elevated blood glucose levels
C. Hepatomegaly
D. Increased susceptibility to infections
E. Jaundice
Correct Answer: B. Elevated blood glucose levels
• Explanation: Galactosemia results from the inability to metabolize galactose due to an enzymatic deficiency (most commonly galactose-1-phosphate uridyltransferase). This condition does not cause elevated blood glucose levels; in fact, hypoglycemia is a more likely finding due to impaired liver function and disrupted glycogen metabolism.
Incorrect options:
A. Cataracts
• Explanation: Cataracts are a classic manifestation of galactosemia caused by the accumulation of galactitol in the lens. This occurs when excess galactose is converted to galactitol by aldose reductase, leading to osmotic stress and lens clouding.
C. Hepatomegaly
• Explanation: Hepatomegaly is a common finding in galactosemia due to liver damage caused by the accumulation of toxic metabolites like galactose-1-phosphate, which interferes with liver function and causes swelling of the liver.
D. Increased susceptibility to infections
• Explanation: Children with galactosemia are particularly susceptible to infections, especially E. coli sepsis. This increased risk is due to immune dysfunction and the systemic effects of toxic metabolite accumulation.
E. Jaundice
• Explanation: Jaundice is a typical feature of galactosemia, resulting from liver dysfunction and the inability to conjugate bilirubin properly due to toxic metabolite interference in hepatic pathways.
8. A 6-week-old infant is brought to the pediatric clinic by his parents. They report that he seems distressed after feedings, often leading to refusal of feeds. Blood work reveals liver and kidney dysfunction, and neurological assessments hint at some brain abnormalities. The metabolic profile shows a buildup of the toxic compound, galactose-1-P. Which of the following enzymatic reactions is likely impaired in this infant?
A. Galactose to Galactose-1-P
B. Galactose-1-P to Glucose-1-P
C. Glucose-1-P to Galactose-1-P
D. Glucose-1-P to Glucose-6-P
E. UDP Galactose to UDP Glucose
Correct Answer: B. Galactose-1-P to Glucose-1-P
• Explanation: The enzymatic reaction that converts galactose-1-phosphate (Galactose-1-P) to glucose-1-phosphate (Glucose-1-P) is catalyzed by galactose-1-phosphate uridyltransferase (GALT). A deficiency in GALT leads to the accumulation of galactose-1-phosphate, which is toxic to the liver, kidneys, and brain. This enzymatic block is the hallmark of Classical Galactosemia and explains the infant’s symptoms, including feeding distress, liver dysfunction, and neurological abnormalities.
Incorrect options:
A. Galactose to Galactose-1-P
• Explanation: This reaction is catalyzed by galactokinase, which phosphorylates galactose to galactose-1-phosphate. While a deficiency in galactokinase can also cause elevated galactose-1-phosphate levels, it is less severe than GALT deficiency and primarily causes cataracts without significant liver or neurological involvement.
C. Glucose-1-P to Galactose-1-P
• Explanation: This reaction is not part of the galactose metabolism pathway. Instead, glucose-1-phosphate is involved in glycogen metabolism and does not convert to galactose-1-phosphate. This option is irrelevant to the case.
D. Glucose-1-P to Glucose-6-P
• Explanation: This reaction is part of glycogenolysis, catalyzed by phosphoglucomutase. It is unrelated to the galactose pathway and would not explain the buildup of galactose-1-phosphate in this infant.
E. UDP Galactose to UDP Glucose
• Explanation: This reaction is catalyzed by UDP-galactose-4-epimerase, an enzyme further downstream in the galactose metabolism pathway. While this enzyme is essential for the interconversion of UDP-galactose and UDP-glucose, its deficiency does not lead to the accumulation of galactose-1-phosphate.
9. A 54-year-old man diagnosed with Type 1 diabetes consults an ophthalmologist due to deteriorating vision. Upon examination, the early stages of a cataract are detected. Given his diabetic condition, which enzyme is most likely to contribute to cataract formation in this patient?
A. Aldolase
B. Aldose reductase
C. Fructokinase
D. Hexokinase
E. Sorbitol dehydrogenase
Correct Answer: B. Aldose reductase
• Explanation: Aldose reductase is the enzyme responsible for converting glucose to sorbitol in the polyol pathway, which becomes active in hyperglycemic conditions such as diabetes. Sorbitol accumulates in tissues like the lens of the eye because its conversion to fructose by sorbitol dehydrogenase is slow or limited. The accumulation of sorbitol causes osmotic stress, leading to lens clouding and cataract formation, which is common in diabetic patients.
Incorrect options:
A. Aldolase
• Explanation: Aldolase is involved in glycolysis and fructose metabolism, but it is not part of the polyol pathway. It does not play a role in cataract formation related to diabetes.
C. Fructokinase
• Explanation: Fructokinase catalyzes the phosphorylation of fructose to fructose-1-phosphate. It is not involved in glucose metabolism or the polyol pathway, making it irrelevant to cataract formation in diabetes.
D. Hexokinase
• Explanation: Hexokinase phosphorylates glucose to glucose-6-phosphate in glycolysis. While it plays a role in normal glucose metabolism, it does not contribute to the sorbitol accumulation that causes cataracts in diabetes.
E. Sorbitol dehydrogenase
• Explanation: Sorbitol dehydrogenase converts sorbitol to fructose in the polyol pathway. While it can reduce sorbitol levels, its activity is relatively slow in certain tissues like the lens, leading to sorbitol accumulation when glucose levels are elevated. However, the primary culprit in sorbitol buildup is aldose reductase.
10. A student studying nutrition read a statement, “Fructose is not a direct energy source for muscles and the brain.” Curious about the underlying reasons, the student researched to understand why certain tissues might not utilize fructose directly. The lack of which of the following in both muscle and brain explains the statement?
A. Fructokinase
B. GLUT2 transporters
C. GLUT2 transporters and Fructokinase
D. GLUT5 transporters
E. GLUT5 transporters and Fructokinase
Correct Answer: E. GLUT5 transporters and Fructokinase
• Explanation: Fructose is absorbed into cells via GLUT5 transporters, which are specific for fructose. These transporters are highly expressed in the intestine and liver but are absent or expressed at low levels in muscle and brain tissues. Additionally, fructose metabolism begins with phosphorylation by fructokinase, an enzyme primarily found in the liver and kidney. The absence of both GLUT5 transporters and fructokinase in muscle and brain tissues limits the ability of these tissues to utilize fructose directly as an energy source. Instead, fructose is metabolized in the liver and converted into glucose or other intermediates that can then be used by these tissues.
Incorrect options:
A. Fructokinase
• Explanation: While fructokinase is crucial for fructose metabolism, its absence alone does not fully explain why muscles and the brain cannot directly utilize fructose. The lack of fructose transport into these tissues (via GLUT5) is also a key factor.
B. GLUT2 transporters
• Explanation: GLUT2 transporters are primarily responsible for transporting glucose and galactose into hepatocytes, pancreatic β-cells, and some other tissues. They do not play a significant role in fructose uptake in the brain or muscles.
C. GLUT2 transporters and Fructokinase
• Explanation: GLUT2 transporters are not the primary transporters for fructose. Therefore, their absence does not explain the inability of muscle and brain tissues to utilize fructose directly.
D. GLUT5 transporters
• Explanation: GLUT5 is the primary transporter for fructose uptake, and its absence in muscle and brain is one reason fructose cannot be utilized directly. However, the absence of fructokinase also contributes significantly to this limitation.
11. Which of the following enzymes catalyzes the last step of lactose biosynthesis in lactating mammary glands?
A. Epimerase
B. Galactokinase
C. Lactose synthase
D. Phosphoglucomutase
E. UDP-Glucose Pyrophosphorylase
Correct Answer: C. Lactose synthase
• Explanation: Lactose synthase catalyzes the final step of lactose biosynthesis in the lactating mammary gland. It combines UDP-galactose and glucose to form lactose and UDP. Lactose synthase is a complex enzyme consisting of two subunits: β-1,4-galactosyltransferase and α-lactalbumin, where α-lactalbumin lowers the Km of the enzyme for glucose, enabling efficient lactose synthesis during lactation.
Incorrect options
A. Epimerase
• Explanation: UDP-galactose-4-epimerase catalyzes the conversion of UDP-galactose to UDP-glucose. While important in galactose metabolism, it does not play a role in the final step of lactose biosynthesis.
B. Galactokinase
• Explanation: Galactokinase phosphorylates galactose to galactose-1-phosphate in the initial step of galactose metabolism. It is unrelated to lactose biosynthesis.
D. Phosphoglucomutase
• Explanation: Phosphoglucomutase catalyzes the conversion of glucose-1-phosphate to glucose-6-phosphate. It is part of carbohydrate metabolism but is not directly involved in lactose synthesis.
E. UDP-Glucose Pyrophosphorylase
• Explanation: UDP-glucose pyrophosphorylase catalyzes the formation of UDP-glucose from glucose-1-phosphate and UTP. While UDP-glucose is a precursor in lactose biosynthesis, this enzyme does not catalyze the final step.
12. Fructose metabolism is related to increased lipogenesis. Which of the following metabolic pathways best explains this observation?
A. Fructose is directly converted to pyruvate, fueling the Krebs cycle
B. Fructose-1-phosphate enters glycolysis after the phosphofructokinase-1 step, producing excess acetyl-CoA
C. Fructose increases hepatic gluconeogenesis, depleting ATP reserves
D. Fructokinase activity is tightly regulated, enhancing fatty acid synthesis
E. Fructose metabolism directly increases glycogen synthesis, diverting glucose to lipids
Correct Answer: B.Fructose-1-phosphate enters glycolysis after the phosphofructokinase-1 step, producing excess acetyl-CoA.
• Explanation: Fructose is phosphorylated by fructokinase to fructose-1-phosphate and then cleaved by aldolase B to form dihydroxyacetone phosphate (DHAP) and glyceraldehyde. These intermediates bypass phosphofructokinase-1, resulting in unregulated glycolysis and excess acetyl-CoA production, which fuels lipogenesis.
Incorrect options:
A. Fructose is not directly converted to pyruvate; it enters glycolysis downstream of key regulatory steps.
C. Fructose does not increase hepatic gluconeogenesis but rather lipogenesis.
D. Fructokinase is not regulated; this lack of control contributes to lipogenesis.
E. Fructose metabolism does not promote glycogen synthesis directly.
13. How does a defect in galactose-1-phosphate uridyltransferase (GALT) potentially affect brain development?
A. UDP-galactose cannot be formed, impairing myelin synthesis and causing neurological deficits.
B. Excess galactose-1-phosphate disrupts glycolysis, starving neurons of energy
C. The inability to metabolize galactose leads to hyperglycemia, damaging neuronal tissue
D. Galactose accumulation impairs neurotransmitter synthesis
E. Galactose is diverted to the polyol pathway, leading to osmotic stress in the brain
Correct Answer: A. UDP-galactose cannot be formed, impairing myelin synthesis and causing neurological deficits.
• Explanation: GALT deficiency in galactosemia prevents the formation of UDP-galactose from galactose-1-phosphate. UDP-galactose is vital for synthesizing galactolipids, which are critical for myelination. This can lead to neurological deficits in untreated galactosemia.
Incorrect options:
B. Excess galactose-1-phosphate disrupts glycolysis, starving neurons of energy
Explanation: Excess galactose-1-phosphate affects energy pathways but doesn’t directly starve neurons.
C. The inability to metabolize galactose leads to hyperglycemia, damaging neuronal tissue.
Explanation: Galactose metabolism does not cause hyperglycemia but toxic metabolite accumulation.
D. Galactose accumulation impairs neurotransmitter synthesis
Explanation: Galactose metabolism is unrelated to neurotransmitter synthesis
E. Galactose is diverted to the polyol pathway, leading to osmotic stress in the brain
Explanation: Osmotic stress occurs in the lens, not the brain, in galactosemia.
