Glycolysis

Glycolysis US Medical PG Question 1: A 4-month-old boy is brought to his pediatrician for a well-child visit. His parents have noticed that he has had poor growth compared to his older siblings. The boy was delivered vaginally after a normal pregnancy. His temperature is 98.8°F (37.1°C), blood pressure is 98/68 mmHg, pulse is 88/min, and respirations are 20/min. On exam, his abdomen appears protuberant, and the boy appears to have abnormally enlarged cheeks. A finger stick reveals that the patient’s fasting blood glucose is 50 mg/dL. On further laboratory testing, the patient is found to have elevated blood lactate levels, as well as no response to a glucagon stimulation test. What enzymatic defect is most likely present?

• A. Alpha-1,4-glucosidase
• B. Glycogen synthase
• C. Alpha-1,6-glucosidase
• D. Glucose-6-phosphatase (Correct Answer)
• E. Glycogen phosphorylase

Glycolysis Explanation: ***Glucose-6-phosphatase*** - The patient's symptoms, including **hypoglycemia**, **hepatomegaly** (implied by protuberant abdomen), **lactic acidosis** (elevated lactate), and lack of response to **glucagon stimulation**, are classic for **Type I glycogen storage disease (von Gierke disease)**, which is caused by a deficiency in **glucose-6-phosphatase**. - This enzyme is crucial for the final step of both **glycogenolysis** and **gluconeogenesis**, and its deficiency prevents the liver from releasing glucose into the bloodstream, leading to severe hypoglycemia. *Alpha-1,4-glucosidase* - A deficiency in **alpha-1,4-glucosidase (acid maltase)** causes **Type II glycogen storage disease (Pompe disease)**, which primarily affects muscle (cardiac and skeletal). - Symptoms include **cardiomyopathy**, **hypotonia**, and muscle weakness, and it does **not** typically present with hypoglycemia or lactic acidosis. *Glycogen synthase* - A deficiency in **glycogen synthase** would lead to an inability to synthesize glycogen, resulting in **hypoglycemia** but **low** (rather than high) glycogen levels. - Patients typically experience fasting hypoglycemia, but **no hepatomegaly** or lactic acidosis would be expected. *Alpha-1,6-glucosidase* - A deficiency in **alpha-1,6-glucosidase (debranching enzyme)** causes **Type III glycogen storage disease (Cori disease)**. - This condition presents with **hepatomegaly**, **hypoglycemia**, and sometimes muscle weakness, but patients typically **do respond to glucagon** and have less severe lactic acidosis compared to Type I. *Glycogen phosphorylase* - A deficiency in **glycogen phosphorylase (hepatic form, Type VI GSD or Hers disease)** primarily affects the liver's ability to break down glycogen. - This typically causes **hepatomegaly** and **hypoglycemia**, but usually, the patients **respond to glucagon** because other pathways for glucose release (like gluconeogenesis) are intact.

Glycolysis US Medical PG Question 2: Certain glucose transporters that are expressed predominantly on skeletal muscle cells and adipocytes are unique compared to those transporters found on other cell types within the body. Without directly affecting glucose transport in other cell types, which of the following would be most likely to selectively increase glucose uptake in skeletal muscle cells and adipocytes?

• A. Increased plasma glucose concentration
• B. It is physiologically impossible to selectively increase glucose uptake in specific cells
• C. Increased levels of circulating insulin (Correct Answer)
• D. Decreased plasma glucose concentration
• E. Decreased levels of circulating insulin

Glycolysis Explanation: ***Increased levels of circulating insulin*** - Insulin stimulates the translocation of **GLUT4 transporters** from intracellular vesicles to the cell membrane in **skeletal muscle** and **adipocytes**, thereby increasing glucose uptake. - This mechanism is **selective** because other cell types (e.g., brain, liver) primarily use insulin-independent glucose transporters (e.g., GLUT1, GLUT2, GLUT3) that are constitutively active or respond to different signals. *Increased plasma glucose concentration* - While increased glucose concentration would drive glucose uptake in many cells, it is not **selective** for skeletal muscle and adipocytes since other cells also take up glucose. - Insulin-independent tissues would also increase glucose uptake, making this a non-specific effect. *It is physiologically impossible to selectively increase glucose uptake in specific cells* - This statement is incorrect because the body has mechanisms, such as **insulin-mediated GLUT4 translocation**, that specifically regulate glucose uptake in certain cell types like skeletal muscle and adipocytes. - This regulatory specificity is crucial for maintaining **glucose homeostasis**. *Decreased plasma glucose concentration* - A decrease in plasma glucose would generally **reduce** glucose uptake across all cell types, including skeletal muscle and adipocytes. - It would not selectively increase uptake in any specific cell population. *Decreased levels of circulating insulin* - Decreased insulin levels would lead to **reduced** glucose uptake in insulin-sensitive tissues like skeletal muscle and adipocytes, as GLUT4 transporters would remain sequestered intracellularly. - This would result in higher circulating glucose levels rather than increased uptake.

Glycolysis US Medical PG Question 3: A 14-year-old female with no past medical history presents to the emergency department with nausea and abdominal pain. On physical examination, her blood pressure is 78/65, her respiratory rate is 30, her breath has a fruity odor, and capillary refill is > 3 seconds. Serum glucose is 820 mg/dL. After starting IV fluids, what is the next best step in the management of this patient?

• A. Intravenous Dextrose in water
• B. Subcutaneous insulin glargine
• C. Intravenous regular insulin (Correct Answer)
• D. Intravenous glucagon
• E. Subcutaneous insulin lispro

Glycolysis Explanation: ***Intravenous regular insulin*** - The patient presents with **diabetic ketoacidosis (DKA)**, characterized by **hyperglycemia**, **fruity breath** (due to ketones), and **hypotension**. Prompt administration of **intravenous regular insulin** is crucial to lower blood glucose and resolve ketoacidosis. - **Regular insulin** is preferred intravenously due to its **rapid onset** and short duration of action, allowing for precise titration and continuous adjustment based on glucose levels. *Intravenous Dextrose in water* - **Dextrose** would further increase the already severely elevated blood glucose level in a patient with DKA, worsening the metabolic derangements. - Dextrose is typically initiated only after blood glucose drops to safe levels (<200 mg/dL) to prevent **hypoglycemia** during insulin infusion. *Subcutaneous insulin glargine* - **Insulin glargine** is a **long-acting insulin** designed for basal insulin coverage, not for acute management of severe hyperglycemia or DKA. - Its **slow onset of action** and prolonged effect make it unsuitable for the urgent and rapid glucose reduction required in DKA. *Intravenous glucagon* - **Glucagon** is a hormone that **raises blood glucose levels**, counteracting the effects of insulin. - Administering glucagon would exacerbate the severe hyperglycemia present in DKA and is used only in cases of severe hypoglycemia. *Subcutaneous insulin lispro* - **Insulin lispro** is a **rapid-acting insulin analog** but is typically given subcutaneously. - While faster than regular insulin subcutaneously, the **subcutaneous route** has variable absorption in critically ill patients, and the immediate and precisely controllable effect of intravenous regular insulin is needed in DKA.

Glycolysis US Medical PG Question 4: An 11-year-old boy is brought to the emergency room with acute abdominal pain and hematuria. Past medical history is significant for malaria. On physical examination, he has jaundice and a generalized pallor. His hemoglobin is 5 g/dL, and his peripheral blood smear reveals fragmented RBC, microspherocytes, and eccentrocytes (bite cells). Which of the following reactions catalyzed by the enzyme is most likely deficient in this patient?

• A. Glucose-1-phosphate + UTP → UDP-glucose + pyrophosphate
• B. Glucose + ATP → Glucose-6-phosphate + ADP + H+
• C. D-glucose 6-phosphate → D-fructose-6-phosphate
• D. Glucose-6-phosphate + H2O → glucose + Pi
• E. D-glucose-6-phosphate + NADP+ → 6-phospho-D-glucono-1,5-lactone + NADPH + H+ (Correct Answer)

Glycolysis Explanation: ***D-glucose-6-phosphate + NADP+ → 6-phospho-D-glucono-1,5-lactone + NADPH + H+*** - This reaction is catalyzed by **glucose-6-phosphate dehydrogenase (G6PD)**, an enzyme critical for the production of **NADPH** in the **pentose phosphate pathway**. - **NADPH** is essential for reducing **oxidative stress** in red blood cells. A deficiency in G6PD leads to increased susceptibility to hemolysis, especially under oxidative triggers like malaria, resulting in symptoms such as **acute hemolytic anemia**, jaundice, and specific morphological changes (e.g., **fragmented RBCs**, **microspherocytes**, and **eccentrocytes**, also known as **bite cells**). *Glucose-1-phosphate + UTP → UDP-glucose + pyrophosphate* - This reaction is catalyzed by **UDP-glucose pyrophosphorylase** and is important for **glycogen synthesis**. - A deficiency in this enzyme would primarily affect glycogen metabolism and would not explain the **hemolytic anemia** or the characteristic red blood cell morphology seen in the patient. *Glucose + ATP → Glucose-6-phosphate + ADP + H+* - This reaction is catalyzed by **hexokinase**, the first committed step in **glycolysis**. - While hexokinase deficiency can cause **hemolytic anemia**, it generally presents with chronic, moderate anemia and does not typically involve the specific red blood cell morphology (eccentrocytes/bite cells) associated with oxidative damage found in G6PD deficiency. *D-glucose 6-phosphate → D-fructose-6-phosphate* - This reaction is catalyzed by **phosphoglucose isomerase** (also known as phosphohexose isomerase) and is part of **glycolysis**. - A deficiency in this enzyme would impair glycolysis and lead to **hemolytic anemia**, but its clinical presentation and RBC morphology differ from what is typically seen in G6PD deficiency, particularly the absence of oxidative stress markers like bite cells. *Glucose-6-phosphate + H2O → glucose + Pi* - This reaction is catalyzed by **glucose-6-phosphatase**, an enzyme found primarily in the liver and kidney, responsible for the final step in **gluconeogenesis** and glycogenolysis to release free glucose into the bloodstream. - A deficiency in glucose-6-phosphatase leads to **glycogen storage disease type I (Von Gierke's disease)**, characterized by **hypoglycemia**, **lactic acidosis**, and hepatomegaly, not hemolytic anemia.

Glycolysis US Medical PG Question 5: An 8-year old boy is brought to the emergency department because he has been lethargic and has had several episodes of nausea and vomiting for the past day. He has also had increased thirst over the past two months. He has lost 5.4 kg (11.9 lbs) during this time. He is otherwise healthy and has no history of serious illness. His temperature is 37.5 °C (99.5 °F), blood pressure is 95/68 mm Hg, pulse is 110/min, and respirations are 30/min. He is somnolent and slightly confused. His mucous membranes are dry. Laboratory studies show: Hemoglobin 16.2 g/dL Leukocyte count 9,500/mm3 Platelet count 380,000/mm3 Serum Na+ 130 mEq/L K+ 5.5 mEq/L Cl- 99 mEq/L HCO3- 16 mEq/L Creatinine 1.2 mg/dL Glucose 570 mg/dL Ketones positive Blood gases, arterial pH 7.25 pCO2 21 mm Hg Which of the following is the most appropriate next step in management?

• A. Intravenous hydration with 0.45% normal saline and insulin
• B. Intravenous hydration with 5% dextrose solution and 0.45% normal saline
• C. Intravenous sodium bicarbonate
• D. Intravenous hydration with 0.9% normal saline and insulin (Correct Answer)
• E. Intravenous hydration with 0.9% normal saline and potassium chloride

Glycolysis Explanation: ***Intravenous hydration with 0.9% normal saline and insulin*** - This patient presents with **diabetic ketoacidosis (DKA)**, characterized by hyperglycemia (glucose 570 mg/dL), metabolic acidosis (pH 7.25, HCO3- 16 mEq/L, ketones positive), and dehydration (dry mucous membranes, increased thirst, weight loss). - Initial management of DKA involves aggressive **volume expansion** with **0.9% normal saline** to restore perfusion and reduce hyperglycemia; subsequently, **insulin infusion** is started to correct hyperglycemia and halt ketogenesis. *Intravenous hydration with 0.45% normal saline and insulin* - While insulin is crucial, **0.45% normal saline (hypotonic saline)** is generally not the initial fluid of choice for DKA due to the risk of exacerbating cerebral edema, especially in children. - **Isotonic saline (0.9% normal saline)** is preferred for initial resuscitation to rapidly restore extracellular fluid volume. *Intravenous hydration with 5% dextrose solution and 0.45% normal saline* - **5% dextrose solution** should only be added to intravenous fluids when the blood glucose level falls to around 200-250 mg/dL, to prevent hypoglycemia while continuing insulin to resolve ketosis. - Administering dextrose initially would worsen the existing severe hyperglycemia. *Intravenous sodium bicarbonate* - **Sodium bicarbonate** is generally not recommended for mild to moderate DKA due to potential risks like cerebral edema and metabolic alkalosis, and potential paradoxical worsening of CNS acidosis. - Bicarbonate therapy is reserved for **severe acidosis (pH < 6.9 or 7.0)** with hemodynamic instability or impaired cardiac contractility, which is not the case here. *Intravenous hydration with 0.9% normal saline and potassium chloride* - While **0.9% normal saline** is appropriate, this option lacks **insulin therapy**, which is essential for treating DKA by halting ketogenesis and correcting hyperglycemia. - Although potassium supplementation will be necessary during DKA treatment (as insulin drives K+ into cells and can cause hypokalemia), the most appropriate **next step** is to initiate both fluid resuscitation and insulin therapy together. - The patient's current potassium level of 5.5 mEq/L is at the upper limit of normal, but reflects total body potassium depletion; potassium should be added to maintenance fluids once adequate urine output is established.

Glycolysis US Medical PG Question 6: The balance between glycolysis and gluconeogenesis is regulated at several steps, and accumulation of one or more products/chemicals can either promote or inhibit one or more enzymes in either pathway. Which of the following molecules if increased in concentration can promote gluconeogenesis?

• A. ADP
• B. Acetyl-CoA (Correct Answer)
• C. AMP
• D. Fructose-2,6-bisphosphate
• E. Insulin

Glycolysis Explanation: ***Acetyl-CoA*** - **Acetyl-CoA** promotes gluconeogenesis by activating **pyruvate carboxylase**, the enzyme that converts pyruvate to oxaloacetate, effectively pushing the pathway forward. - High levels of **Acetyl-CoA** generally signal a state of abundant energy from fatty acid oxidation, indicating that glucose is not immediately needed for energy and can be synthesized for storage or use elsewhere. *ADP* - **ADP** is a key indicator of low cellular energy and **stimulates** glycolysis while **inhibiting** gluconeogenesis to produce ATP. - Its presence signals a need for energy synthesis rather than glucose production. *AMP* - **AMP** also signals low energy status and is a powerful **allosteric activator** of **phosphofructokinase-1 (PFK-1)**, the rate-limiting enzyme in glycolysis. - Activates **AMP-activated protein kinase (AMPK)**, which promotes catabolic processes like glycolysis and inhibits anabolic processes like gluconeogenesis. *Fructose-2,6-bisphosphate* - **Fructose-2,6-bisphosphate** is a potent **allosteric activator** of **PFK-1** in glycolysis and a strong **inhibitor** of **fructose-1,6-bisphosphatase** in gluconeogenesis. - Its levels increase in response to insulin, promoting glucose utilization and inhibiting glucose production. *Insulin* - **Insulin** is a hormone that **promotes glucose uptake** and utilization by tissues and **inhibits gluconeogenesis**. - It achieves this by activating enzymes involved in glycolysis and glycogen synthesis while inhibiting key enzymes in gluconeogenesis, such as **fructose-1,6-bisphosphatase**.

Glycolysis US Medical PG Question 7: A 22-year-old man presents to his primary care provider because of fever, diarrhea, and abdominal cramps. He has returned from Dhaka, Bangladesh recently where he was visiting his relatives. He is diagnosed with Shigella infection, and ciprofloxacin is started. He develops severe nausea and weakness 2 days later and complains of passing dark urine. The lab test results reveal a hemoglobin level of 7.9 g/dL, increased unconjugated bilirubin, increased reticulocyte count, increased lactate dehydrogenase, and increased blood urea. Which of the following is the best next step for the diagnosis of this patient’s condition?

• A. Direct antiglobulin (Coombs) test
• B. ADAMTS-13 activity assay
• C. Eosin-5-maleimide (EMA) binding test
• D. Hemoglobin electrophoresis
• E. Glucose-6-phosphate dehydrogenase (G6PD) enzyme assay (Correct Answer)

Glycolysis Explanation: ***Glucose-6-phosphate dehydrogenase (G6PD) enzyme assay*** - The patient's symptoms (nausea, weakness, dark urine) and lab findings (hemoglobin 7.9 g/dL, increased unconjugated bilirubin, increased reticulocyte count, increased LDH) indicate **acute hemolytic anemia**. - **Ciprofloxacin** is an oxidant drug, and in a patient with recent travel history to Bangladesh, **glucose-6-phosphate dehydrogenase (G6PD) deficiency** should be strongly considered due to its higher prevalence in populations from South Asia, the Mediterranean, and Africa, and its role in drug-induced hemolysis. - The **G6PD enzyme assay** (quantitative measurement) is the definitive diagnostic test for G6PD deficiency. *Direct antiglobulin (Coombs) test* - This test detects **autoimmune hemolytic anemia** by identifying antibodies or complement components bound to red blood cells. - While the patient has hemolytic anemia, the context of **oxidant drug exposure (ciprofloxacin)** and travel to an endemic area makes G6PD deficiency a more likely cause than an autoimmune process. *ADAMTS-13 activity assay* - This assay is used to diagnose **Thrombotic Thrombocytopenic Purpura (TTP)** by measuring the activity of the ADAMTS13 enzyme. - TTP involves microangiopathic hemolytic anemia, thrombocytopenia, and organ damage; however, the patient's presentation does not include **thrombocytopenia** or other features of TTP, making this diagnosis less likely. *Eosin-5-maleimide (EMA) binding test* - This test is used to diagnose **hereditary spherocytosis**, a condition in which red blood cells have a defective membrane skeleton leading to increased fragility and chronic hemolysis. - While hereditary spherocytosis causes hemolytic anemia, the patient's **acute presentation immediately following ciprofloxacin use** makes G6PD deficiency a more pertinent diagnosis than a chronic hereditary condition. *Hemoglobin electrophoresis* - This test identifies abnormal hemoglobins, such as those found in **thalassemia** or **sickle cell disease**. - These conditions cause chronic hemolytic anemia, but the acute onset of severe hemolysis directly linked to **oxidant drug exposure** is inconsistent with these inherited hemoglobinopathies.

Glycolysis US Medical PG Question 8: A 12-year-old boy and his siblings are referred to a geneticist for evaluation of a mild but chronic hemolytic anemia that has presented with fatigue, splenomegaly, and scleral icterus. Coombs test is negative and blood smear does not show any abnormal findings. An enzymatic panel is assayed, and pyruvate kinase is found to be mutated on both alleles. The geneticist explains that pyruvate kinase functions in glycolysis and is involved in a classic example of feed-forward regulation. Which of the following metabolites is able to activate pyruvate kinase?

• A. Fructose-1,6-bisphosphate (Correct Answer)
• B. Alanine
• C. ATP
• D. Glucose-6-phosphate
• E. Glyceraldehyde-3-phosphate

Glycolysis Explanation: ***Fructose-1,6-bisphosphate*** - **Fructose-1,6-bisphosphate** is a potent **allosteric activator** of pyruvate kinase. This is an example of **feed-forward activation**, where a product of an early irreversible step in glycolysis (catalyzed by phosphofructokinase-1) activates a later enzyme (pyruvate kinase) in the pathway. - This activation ensures that substrates for the later steps of glycolysis are rapidly utilized when earlier steps are highly active, matching the rate of metabolite flow and increasing the overall efficiency of glycolysis for energy production. *Alanine* - **Alanine** is an **inhibitor** of pyruvate kinase, not an activator. It serves as an indicator of a high cellular energy state and ample amino acid supply. - High levels of alanine signal the cell that there is sufficient energy and building blocks, thus **shutting down** glycolysis at the pyruvate kinase step to conserve glucose for other needs like glycogen synthesis. *ATP* - **ATP** (adenosine triphosphate) is an **allosteric inhibitor** of pyruvate kinase. High ATP levels signal a high energy state in the cell. - When the cell has sufficient energy, ATP binds to a regulatory site on pyruvate kinase, reducing its activity and **slowing down glycolysis** to prevent overproduction of ATP. *Glucose-6-phosphate* - **Glucose-6-phosphate** is an intermediate in glycolysis but does not directly activate pyruvate kinase. It can act as an allosteric inhibitor of hexokinase, the first enzyme in glycolysis, but not pyruvate kinase. - Its accumulation typically signifies a **backup** in the glycolytic pathway (e.g., due to downstream inhibition), leading to a *reduction* in overall glucose flux rather than a direct activation of pyruvate kinase. *Glyceraldehyde-3-phosphate* - **Glyceraldehyde-3-phosphate** is an intermediate in glycolysis, but it does not directly activate pyruvate kinase. It is a substrate for glyceraldehyde-3-phosphate dehydrogenase. - While its presence indicates active glycolysis, it does not exert a specific allosteric regulatory effect on pyruvate kinase in the way fructose-1,6-bisphosphate does.

Glycolysis US Medical PG Question 9: A 1-year-old male with a history of recurrent pseudomonal respiratory infections and steatorrhea presents to the pediatrician for a sweat test. The results demonstrate a chloride concentration of 70 mEq/L (nl < 40 mEq/L). Which of the following defects has a similar AUTOSOMAL RECESSIVE mode of inheritance as the disorder experienced by this patient?

• A. Abnormal production of type IV collagen
• B. Trinucleotide repeat expansion of CAG on chromosome 4
• C. Mutated gene for mitochondrial-tRNA-Lys
• D. Accumulation of glycogen in the lysosome (Correct Answer)
• E. Inability to convert carbamoyl phosphate and ornithine into citrulline

Glycolysis Explanation: ***Accumulation of glycogen in the lysosome*** - The patient's symptoms (recurrent **pseudomonal respiratory infections**, **steatorrhea**, and elevated sweat chloride) are classic for **cystic fibrosis (CF)**, an **autosomal recessive** disorder. - Accumulation of glycogen in the lysosome describes **Pompe disease (Type II Glycogen Storage Disease)**, which is also an **autosomal recessive** disorder, making this the correct answer. *Abnormal production of type IV collagen* - This defect is characteristic of **Alport syndrome**, which is predominantly **X-linked dominant** (~80-85% of cases), though autosomal recessive forms exist. - The question context and typical board exam framing classify this as X-linked, not autosomal recessive. - Alport syndrome primarily affects the kidneys, ears, and eyes, and does not present with recurrent pseudomonal infections or steatorrhea. *Trinucleotide repeat expansion of CAG on chromosome 4* - This genetic defect is responsible for **Huntington's disease**, which is an **autosomal dominant** neurodegenerative disorder. - Huntington's disease presents with chorea, cognitive decline, and psychiatric symptoms, which are distinct from CF. *Mutated gene for mitochondrial-tRNA-Lys* - A mutated gene for mitochondrial-tRNA-Lys is associated with **MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes)**, which is inherited through **maternal (mitochondrial)** inheritance. - This mode of inheritance is distinct from the autosomal recessive pattern seen in cystic fibrosis. *Inability to convert carbamoyl phosphate and ornithine into citrulline* - This describes a defect in **ornithine transcarbamylase (OTC) deficiency**, an **X-linked recessive** disorder, not autosomal recessive. - OTC deficiency leads to hyperammonemia and metabolic disturbances, without the pulmonary and gastrointestinal symptoms typical of cystic fibrosis.

Glycolysis US Medical PG Question 10: An 11-month-old boy is brought to a pediatrician by his parents with a recurrent cough, which he has had since the age of 2 months. He has required 3 hospitalizations for severe wheezing episodes. His mother also mentions that he often has diarrhea. The boy’s detailed history reveals that he required hospitalization for meconium ileus during the neonatal period. Upon physical examination, his temperature is 37.0°C (98.6ºF), pulse rate is 104/min, respiratory rate is 40/min, and blood pressure is 55/33 mm Hg. An examination of the boy’s respiratory system reveals the presence of bilateral wheezing and scattered crepitations. An examination of his cardiovascular system does not reveal any abnormality. His length is 67.3 cm (26.5 in) and weight is 15 kg (33 lbs). His sweat chloride level is 74 mmol/L. His genetic evaluation confirms that he has an autosomal recessive disorder resulting in a dysfunctional membrane-bound protein. Which of the following best describes the mechanism associated with the most common mutation that causes this disorder?

• A. Decreased chloride transport through the protein
• B. Disordered regulation of the protein
• C. Decreased transcription of the protein due to splicing defect
• D. Complete absence of the protein
• E. Defective maturation and early degradation of the protein (Correct Answer)

Glycolysis Explanation: ***Defective maturation and early degradation of the protein*** - The clinical picture (recurrent cough, wheezing, diarrhea, meconium ileus, elevated sweat chloride, autosomal recessive inheritance) strongly points to **cystic fibrosis (CF)**. The most common mutation in CF is **F508del**, which leads to misfolding of the **CFTR protein**, causing retention in the endoplasmic reticulum and subsequent degradation before reaching the cell membrane. - This **defective processing and early degradation** result in a significant reduction or absence of functional CFTR protein at the cell surface, leading to impaired chloride transport. *Decreased chloride transport through the protein* - While **decreased chloride transport** is the ultimate functional consequence of cystic fibrosis, it is not the direct mechanism associated with the **F508del mutation's impact** on the CFTR protein itself. - This option describes the **physiological result** of the protein defect, not the cellular/molecular mechanism of the most common mutation. *Disordered regulation of the protein* - **Disordered regulation** could be a potential mechanism for some CFTR mutations (Class IV mutations), affecting how the channel opens and closes or responds to signaling. - However, for the **F508del mutation** (Class II mutation), the primary issue is the **lack of properly localized protein** due to misfolding and degradation, rather than a problem with the regulation or gating of the protein once it reaches the membrane. *Decreased transcription of the protein due to splicing defect* - **Decreased transcription** or **splicing defects** (Class I and V mutations) would result in reduced mRNA levels or incorrectly formed mRNA, leading to less protein synthesis. - The **F508del mutation** involves a deletion of three nucleotides in exon 10, leading to a missing phenylalanine at position 508. Importantly, **transcription and splicing occur normally**; the mRNA is produced correctly. The problem arises at the **post-translational level** with protein folding, not at the transcriptional or splicing level. *Complete absence of the protein* - While functional CFTR protein is largely absent at the cell surface in F508del, the protein is **initially synthesized** in the endoplasmic reticulum. - The problem is its **misfolding and rapid degradation**, preventing it from reaching the membrane, rather than a complete failure of protein synthesis from the outset (which would be seen in nonsense or frameshift mutations causing Class I defects).

Glycolysis Flashcard 1 of 10

Question: Pyruvate kinase defiency results in increased levels of _____, which causes decreased Hb affinity for O2

Answer: 2,3-BPG

Glycolysis Flashcard 2 of 10

Question: Hexokinase is characterized by a _____ Vmax relative to glucokinase

Answer: low

Glycolysis Flashcard 3 of 10

Question: Which steps (2) of glycolysis produce ATP? _____

Answer:

Glycolysis Flashcard 4 of 10

Question: Which steps (2) of glycolysis require ATP? _____

Answer:

Glycolysis Flashcard 5 of 10

Question: Pyruvate kinase is regulated via positive feedback by _____ (glycolysis)

Answer: fructose-1,6-bisphosphate

Glycolysis Flashcard 6 of 10

Question: What is the rate-limiting enzyme of glycolysis?_____

Answer: Phosphofructokinase-1 (PFK-1)

Glycolysis Flashcard 7 of 10

Question: phosphofructokinase-2/fructose bisphosphatase-2 (PFK-2/FBP-2)

Answer:

Extra Information: balances glycolysis and gluconeogenesisF-2,6-BP

Glycolysis Flashcard 8 of 10

Question: Where does glycolysis take place?

Answer: cytoplasm

Glycolysis Flashcard 9 of 10

Question: glycolysis

Answer: phosphofructokinase-1 (PFK-1)

Glycolysis Flashcard 10 of 10

Question: What enzyme converts pyruvate to lactate?

Answer: lactate dehydrogenase (LDH)