Topic: Gluconeogenesis
Subtopic: Sites and Regulation
Keyword Definitions:
• Gluconeogenesis: Process of glucose synthesis from non-carbohydrate precursors.
• Liver: Primary site of gluconeogenesis, maintains blood glucose.
• Kidney: Secondary site of gluconeogenesis, especially in prolonged fasting.
• Muscle: Lacks glucose-6-phosphatase, cannot release glucose into blood.
• Gut: Intestinal cells may perform minor gluconeogenesis but not significant.
Lead Question - 2013
Gluconeogenesis occurs in all except?
a) Liver
b) Kidney
c) Gut
d) Muscle
Explanation:
Gluconeogenesis mainly occurs in the liver and kidney. The gut contributes minimally in fasting states. Muscle lacks glucose-6-phosphatase, hence cannot release free glucose into the blood. Therefore, gluconeogenesis does not occur in Muscle (Answer: d). This is a key differentiating feature between hepatic and muscle carbohydrate metabolism.
1) The first committed step in gluconeogenesis is catalyzed by:
a) Pyruvate carboxylase
b) PEP carboxykinase
c) Fructose-1,6-bisphosphatase
d) Glucose-6-phosphatase
Explanation:
The first committed step of gluconeogenesis is the conversion of pyruvate to oxaloacetate, catalyzed by pyruvate carboxylase, requiring biotin and ATP. This distinguishes it from glycolysis reversal. Thus, the correct answer is Pyruvate carboxylase (Answer: a). This regulatory step ensures glucose synthesis during fasting or starvation.
2) A patient with biotin deficiency will have impaired activity of:
a) Pyruvate carboxylase
b) Fructokinase
c) Glucokinase
d) Hexokinase
Explanation:
Biotin is a coenzyme required for carboxylation reactions, including pyruvate carboxylase. Its deficiency impairs gluconeogenesis, leading to hypoglycemia. Fructokinase, glucokinase, and hexokinase do not require biotin. Therefore, the enzyme affected is Pyruvate carboxylase (Answer: a). Clinical features include metabolic acidosis and neurological dysfunction.
3) Cori cycle links muscle glycolysis with hepatic gluconeogenesis by transporting:
a) Pyruvate
b) Lactate
c) Alanine
d) Glycerol
Explanation:
In the Cori cycle, lactate produced by anaerobic glycolysis in muscle is transported to the liver, where it undergoes gluconeogenesis to form glucose. The glucose returns to the muscle. Thus, the correct transported metabolite is Lactate (Answer: b). This cycle helps maintain blood glucose during exercise.
4) A patient with liver failure will have impaired gluconeogenesis leading to:
a) Hyperglycemia
b) Hypoglycemia
c) Hyperlipidemia
d) Gout
Explanation:
The liver is the primary site for gluconeogenesis. In liver failure, inability to generate glucose results in Hypoglycemia (Answer: b). This is especially severe during fasting. Hypoglycemia in such patients is a critical clinical feature requiring glucose infusion for stabilization.
5) Which amino acid is the major gluconeogenic precursor?
a) Alanine
b) Lysine
c) Leucine
d) Valine
Explanation:
Alanine, derived from muscle protein breakdown, is the most important gluconeogenic amino acid. It enters the glucose-alanine cycle, transporting nitrogen to the liver. Lysine and leucine are ketogenic, not gluconeogenic. Therefore, the major precursor is Alanine (Answer: a). This process becomes significant during fasting and starvation.
6) A patient with fasting hypoglycemia and lactic acidosis likely has deficiency of:
a) Glucokinase
b) Glucose-6-phosphatase
c) Hexokinase
d) Phosphofructokinase
Explanation:
Deficiency of glucose-6-phosphatase causes glycogen storage disease type I (von Gierke’s disease), presenting with hypoglycemia and lactic acidosis due to impaired gluconeogenesis and glycogenolysis. Hence, the enzyme deficient is Glucose-6-phosphatase (Answer: b). This condition also shows hepatomegaly and hyperuricemia.
7) Which step in gluconeogenesis bypasses pyruvate kinase?
a) Pyruvate → Oxaloacetate
b) Oxaloacetate → PEP
c) Fructose-1,6-bisphosphate → Fructose-6-phosphate
d) Glucose-6-phosphate → Glucose
Explanation:
Pyruvate kinase is bypassed by the two-step reaction catalyzed by pyruvate carboxylase and PEP carboxykinase. Together, they convert pyruvate into phosphoenolpyruvate. Thus, the bypass step is Pyruvate → Oxaloacetate and Oxaloacetate → PEP (Answer: a & b combined). This ensures irreversible steps of glycolysis are circumvented.
8) A malnourished alcoholic patient is given glucose infusion and develops lactic acidosis. The likely deficiency is:
a) Thiamine
b) Biotin
c) Vitamin C
d) Vitamin K
Explanation:
Alcoholics often develop thiamine deficiency. Without thiamine, pyruvate cannot enter the TCA cycle via PDH, leading to shunting of pyruvate to lactate, causing lactic acidosis. Therefore, the deficiency is Thiamine (Answer: a). Giving glucose without thiamine supplementation worsens this condition clinically (Wernicke encephalopathy risk).
9) Glycerol enters gluconeogenesis after conversion to:
a) Glycerol-3-phosphate
b) Dihydroxyacetone phosphate
c) Pyruvate
d) Acetyl-CoA
Explanation:
Glycerol released from lipolysis is converted to glycerol-3-phosphate by glycerol kinase, then oxidized to dihydroxyacetone phosphate, which enters gluconeogenesis. Thus, the correct intermediate is Dihydroxyacetone phosphate (Answer: b). This pathway becomes significant during prolonged fasting when triglycerides are mobilized.
10) A child with hepatomegaly, hypoglycemia, and increased blood lactate is suspected of having:
a) Von Gierke’s disease
b) McArdle’s disease
c) Pompe’s disease
d) Hers’ disease
Explanation:
Von Gierke’s disease (Type I glycogen storage disease) results from glucose-6-phosphatase deficiency. It presents with hepatomegaly, severe fasting hypoglycemia, lactic acidosis, and hyperuricemia. Thus, the correct answer is Von Gierke’s disease (Answer: a). Early diagnosis and dietary management are crucial to prevent complications.
11) The gluconeogenic enzyme absent in muscle is:
a) Pyruvate carboxylase
b) PEP carboxykinase
c) Fructose-1,6-bisphosphatase
d) Glucose-6-phosphatase
Explanation:
Muscle contains enzymes like pyruvate carboxylase, PEP carboxykinase, and fructose-1,6-bisphosphatase but lacks glucose-6-phosphatase. Hence, it cannot release free glucose into the bloodstream. Therefore, the absent enzyme is Glucose-6-phosphatase (Answer: d). This is why gluconeogenesis in muscle does not contribute to blood glucose regulation.
Topic: Gluconeogenesis
Subtopic: Substrates and Regulation
Keyword Definitions:
• Gluconeogenesis: Formation of glucose from non-carbohydrate precursors.
• Alanine: A major gluconeogenic amino acid from muscle breakdown.
• Lactate: Produced in anaerobic glycolysis, converted back to glucose via Cori cycle.
• Glycerol: Derived from triglycerides, enters gluconeogenesis via DHAP.
• Muscle: Lacks glucose-6-phosphatase, hence cannot release glucose.
Lead Question - 2013
True about gluconeogenesis?
a) Occurs mainly in muscle
b) It is reverse of glycolysis
c) Alanine & lactate both can serve as substrate
d) Glycerol is not a substrate
Explanation:
Gluconeogenesis occurs mainly in liver and kidney, not in muscle. It is not a complete reversal of glycolysis because bypass reactions are required. Both alanine and lactate act as substrates. Glycerol also serves as a precursor. Correct statement is Alanine & lactate both can serve as substrate (Answer: c).
1) Which of the following is not a gluconeogenic substrate?
a) Alanine
b) Lactate
c) Glycerol
d) Acetyl-CoA
Explanation:
Alanine, lactate, and glycerol enter gluconeogenesis to form glucose. Acetyl-CoA cannot be converted into glucose due to irreversible pyruvate dehydrogenase reaction. Thus, the correct answer is Acetyl-CoA (Answer: d). This is why fatty acids with even carbons do not contribute to glucose production during fasting.
2) A patient with uncontrolled diabetes develops high ketone bodies. Which substrate fails to support gluconeogenesis due to lack of oxaloacetate?
a) Alanine
b) Lactate
c) Acetyl-CoA
d) Glycerol
Explanation:
Acetyl-CoA cannot support gluconeogenesis because it requires oxaloacetate for entry into TCA cycle. In diabetes, oxaloacetate is diverted to gluconeogenesis, leaving acetyl-CoA for ketone body formation. Thus, the substrate unable to produce glucose is Acetyl-CoA (Answer: c). This leads to diabetic ketoacidosis in clinical practice.
3) The first enzyme unique to gluconeogenesis is:
a) Pyruvate carboxylase
b) Hexokinase
c) Phosphofructokinase-1
d) Pyruvate kinase
Explanation:
Pyruvate carboxylase catalyzes the conversion of pyruvate to oxaloacetate in mitochondria, the first committed step in gluconeogenesis. It requires biotin and ATP. Hexokinase and PFK-1 belong to glycolysis, and pyruvate kinase is bypassed in gluconeogenesis. Thus, the correct answer is Pyruvate carboxylase (Answer: a). It is a regulated mitochondrial enzyme.
4) A child presents with fasting hypoglycemia and hepatomegaly. Enzyme deficiency likely is:
a) Pyruvate kinase
b) Glucose-6-phosphatase
c) Citrate synthase
d) PFK-2
Explanation:
Deficiency of glucose-6-phosphatase causes von Gierke’s disease (GSD type I). Patients present with fasting hypoglycemia, lactic acidosis, hepatomegaly, and hyperuricemia. Other enzymes listed are not related to gluconeogenesis impairment. Thus, the deficient enzyme is Glucose-6-phosphatase (Answer: b). It is located in the endoplasmic reticulum of hepatocytes.
5) In Cori cycle, lactate from muscle is transported to:
a) Brain
b) Adipose tissue
c) Liver
d) Kidney
Explanation:
In the Cori cycle, lactate generated by anaerobic glycolysis in muscle is transported via blood to the liver. Here, it undergoes gluconeogenesis to produce glucose, which is sent back to muscle. Thus, the site is Liver (Answer: c). This cycle helps sustain glucose supply during anaerobic exercise.
6) A patient with biotin deficiency will have impaired activity of:
a) Pyruvate carboxylase
b) Hexokinase
c) Fructokinase
d) PFK-1
Explanation:
Biotin acts as a cofactor for carboxylase enzymes, including pyruvate carboxylase. Its deficiency impairs gluconeogenesis and leads to hypoglycemia, metabolic acidosis, and neurological symptoms. Hexokinase, fructokinase, and PFK-1 do not require biotin. Thus, the enzyme affected is Pyruvate carboxylase (Answer: a). Egg white diet can predispose to this deficiency.
7) Which of the following bypasses the irreversible step of PFK-1 in gluconeogenesis?
a) Glucose-6-phosphatase
b) Fructose-1,6-bisphosphatase
c) PEP carboxykinase
d) Pyruvate carboxylase
Explanation:
The irreversible step catalyzed by phosphofructokinase-1 in glycolysis is bypassed by fructose-1,6-bisphosphatase in gluconeogenesis. This enzyme hydrolyzes fructose-1,6-bisphosphate to fructose-6-phosphate. Hence, the correct answer is Fructose-1,6-bisphosphatase (Answer: b). It is a major regulatory point inhibited by AMP and fructose-2,6-bisphosphate.
8) A patient with liver disease shows impaired gluconeogenesis from alanine. The enzyme likely defective is:
a) Alanine aminotransferase
b) Glucokinase
c) Hexokinase
d) Pyruvate kinase
Explanation:
Alanine aminotransferase converts alanine to pyruvate, which then enters gluconeogenesis. Impairment leads to reduced glucose production, causing hypoglycemia in fasting states. Glucokinase and hexokinase are glycolytic enzymes, and pyruvate kinase is not involved here. Thus, the enzyme defective is Alanine aminotransferase (Answer: a). ALT levels are also markers of liver injury.
9) Which of the following hormones stimulates gluconeogenesis?
a) Insulin
b) Glucagon
c) ADH
d) Calcitonin
Explanation:
Glucagon stimulates gluconeogenesis by increasing transcription of PEP carboxykinase and fructose-1,6-bisphosphatase, while insulin suppresses the process. ADH and calcitonin do not regulate glucose metabolism directly. Thus, the hormone stimulating gluconeogenesis is Glucagon (Answer: b). Cortisol also plays a role in prolonged fasting by increasing substrate availability.
10) Which of the following best explains why fatty acids cannot serve as gluconeogenic precursors?
a) Lack of NADH
b) Irreversible conversion of pyruvate to acetyl-CoA
c) Absence of carnitine
d) Direct oxidation in mitochondria
Explanation:
Fatty acids produce acetyl-CoA, but the PDH reaction is irreversible, preventing conversion back to pyruvate for gluconeogenesis. Therefore, fatty acids cannot generate glucose. The correct answer is Irreversible conversion of pyruvate to acetyl-CoA (Answer: b). Only odd-chain fatty acids yield propionyl-CoA, a gluconeogenic substrate.
11) The gluconeogenic enzyme absent in skeletal muscle is:
a) Pyruvate carboxylase
b) PEP carboxykinase
c) Fructose-1,6-bisphosphatase
d) Glucose-6-phosphatase
Explanation:
Muscle contains several gluconeogenic enzymes but lacks glucose-6-phosphatase. Thus, it cannot release free glucose into circulation. Therefore, the absent enzyme is Glucose-6-phosphatase (Answer: d). This ensures that gluconeogenesis in muscle supports its own energy needs rather than contributing to systemic blood glucose regulation.
Topic: Metabolism
Subtopic: Gluconeogenesis
Keyword Definitions:
• Gluconeogenesis: Process of synthesizing glucose from non-carbohydrate sources.
• Lactate: End product of anaerobic glycolysis, used as substrate for gluconeogenesis.
• Pyruvate: Key intermediate formed from lactate and alanine.
• Alanine: Amino acid that can be converted to pyruvate via transamination.
• Cori Cycle: Cycle involving lactate transport from muscle to liver for gluconeogenesis.
Lead Question - 2013
Gluconeogenesis from lactate needs all except ?
a) Transport of lactate from muscle to liver
b) Conversion of lactate to pyruvate
c) Transamination of pyruvate to alanine
d) None of the above
Explanation: Transamination of pyruvate to alanine is not a necessary step for gluconeogenesis from lactate. The main requirement is lactate transport, conversion to pyruvate, and subsequent glucose synthesis via the Cori cycle. Answer: c) Transamination of pyruvate to alanine.
1) Which of the following cycles connects lactate metabolism in muscle with gluconeogenesis in liver?
a) Urea cycle
b) Cori cycle
c) TCA cycle
d) Glyoxylate cycle
Explanation: The Cori cycle describes the conversion of lactate from muscle to glucose in the liver. This prevents lactic acidosis and maintains glucose supply during anaerobic conditions. Answer: b) Cori cycle.
2) A patient with liver failure develops severe lactic acidosis after exercise. Which pathway is defective?
a) Glycolysis
b) Gluconeogenesis
c) Glycogenolysis
d) Pentose phosphate pathway
Explanation: In liver failure, gluconeogenesis is impaired, leading to defective utilization of lactate via the Cori cycle, causing lactic acidosis. Answer: b) Gluconeogenesis.
3) Which enzyme converts lactate to pyruvate in gluconeogenesis?
a) Lactate dehydrogenase
b) Pyruvate kinase
c) Pyruvate carboxylase
d) Alanine transaminase
Explanation: Lactate is oxidized to pyruvate by lactate dehydrogenase, using NAD⁺. This is the first step of lactate utilization in gluconeogenesis. Answer: a) Lactate dehydrogenase.
4) A marathon runner develops increased serum lactate after prolonged activity. Which tissue helps remove it through gluconeogenesis?
a) Brain
b) Liver
c) Muscle
d) RBC
Explanation: The liver removes lactate via gluconeogenesis during exercise, converting it into glucose, which is supplied back to muscles. Answer: b) Liver.
5) In gluconeogenesis, pyruvate is converted to oxaloacetate by:
a) Pyruvate carboxylase
b) Pyruvate kinase
c) Pyruvate dehydrogenase
d) Lactate dehydrogenase
Explanation: Pyruvate carboxylase catalyzes the conversion of pyruvate to oxaloacetate in mitochondria using biotin and ATP. Answer: a) Pyruvate carboxylase.
6) A patient with biotin deficiency is unable to utilize lactate for gluconeogenesis. Which enzyme is impaired?
a) Pyruvate carboxylase
b) PEP carboxykinase
c) Lactate dehydrogenase
d) Pyruvate kinase
Explanation: Pyruvate carboxylase requires biotin. Its deficiency impairs pyruvate to oxaloacetate conversion, blocking gluconeogenesis. Answer: a) Pyruvate carboxylase.
7) Which of the following substrates cannot be used for gluconeogenesis?
a) Glycerol
b) Fatty acids
c) Lactate
d) Alanine
Explanation: Most fatty acids (long-chain) cannot serve as substrates because acetyl-CoA cannot form glucose. Glycerol, lactate, and alanine are gluconeogenic. Answer: b) Fatty acids.
8) In Cori cycle, lactate is produced in:
a) RBC and muscle
b) Brain
c) Liver
d) Kidney
Explanation: Lactate is produced mainly in RBCs (no mitochondria) and active muscles. The liver converts this lactate to glucose. Answer: a) RBC and muscle.
9) Which coenzyme is required for lactate dehydrogenase reaction?
a) NAD⁺/NADH
b) FAD/FADH₂
c) TPP
d) Biotin
Explanation: Lactate dehydrogenase requires NAD⁺/NADH as coenzyme for reversible conversion of lactate and pyruvate. Answer: a) NAD⁺/NADH.
10) A patient with mitochondrial dysfunction cannot carry out pyruvate carboxylase reaction. Which process is impaired?
a) Glycolysis
b) Gluconeogenesis
c) Urea cycle
d) Glycogenolysis
Explanation: Pyruvate carboxylase is mitochondrial and essential for gluconeogenesis. Mitochondrial dysfunction blocks glucose synthesis from lactate. Answer: b) Gluconeogenesis.
Chapter: Biochemistry
Topic: Carbohydrate Metabolism
Subtopic: Glycolysis and Gluconeogenesis
Keyword Definitions:
• Glycolysis: Breakdown of glucose to pyruvate generating ATP.
• Gluconeogenesis: Formation of glucose from non-carbohydrate sources.
• Enzyme: Protein catalyst regulating biochemical reactions.
• Pyruvate kinase: Converts phosphoenolpyruvate to pyruvate.
• PFK (Phosphofructokinase): Key regulatory enzyme of glycolysis.
• Hexokinase: Converts glucose to glucose-6-phosphate.
• Phosphoglycerate kinase: Converts 1,3-BPG to 3-phosphoglycerate.
Lead Question - 2013
Which of the enzyme of glycolysis is a part of gluconeogenesis ?
a) Pyruvate kinase
b) PFK
c) Hexokinase
d) Phosphoglycerate kinase
Explanation: The correct answer is d) Phosphoglycerate kinase. This enzyme catalyzes a reversible step, functioning in both glycolysis and gluconeogenesis. Other listed enzymes catalyze irreversible steps specific to glycolysis. Thus, phosphoglycerate kinase is crucial in energy metabolism, highlighting shared pathways between glucose breakdown and synthesis. Answer is option d.
1) Guessed Question
Which glycolytic enzyme is bypassed in gluconeogenesis?
a) Phosphofructokinase
b) Aldolase
c) Enolase
d) Triose phosphate isomerase
Explanation: The correct answer is a) Phosphofructokinase. This irreversible step is bypassed by fructose-1,6-bisphosphatase in gluconeogenesis. Bypass reactions are necessary to overcome energy barriers of irreversible glycolytic steps. Understanding these bypasses is key in metabolic regulation and clinical disorders of glucose metabolism. Answer is option a.
2) Guessed Question
A patient with hypoglycemia after fasting likely has a deficiency in which gluconeogenic enzyme?
a) Glucose-6-phosphatase
b) Enolase
c) Phosphoglycerate mutase
d) Pyruvate kinase
Explanation: The correct answer is a) Glucose-6-phosphatase. Deficiency causes impaired gluconeogenesis and glycogenolysis, leading to fasting hypoglycemia, hepatomegaly, and lactic acidosis (Von Gierke’s disease). This enzyme is crucial for final glucose release into blood. Clinically, patients present with severe fasting intolerance. Answer is option a.
3) Guessed Question
Which cofactor is essential for pyruvate carboxylase in gluconeogenesis?
a) Thiamine
b) Biotin
c) Riboflavin
d) Niacin
Explanation: The correct answer is b) Biotin. Pyruvate carboxylase requires biotin as a coenzyme to catalyze the conversion of pyruvate to oxaloacetate in mitochondria. Biotin deficiency can impair gluconeogenesis, leading to hypoglycemia and metabolic disturbances. This highlights the importance of vitamins as enzyme cofactors. Answer is option b.
4) Guessed Question
Which of the following is an irreversible enzyme of glycolysis?
a) Hexokinase
b) Phosphoglycerate kinase
c) Enolase
d) Triose phosphate isomerase
Explanation: The correct answer is a) Hexokinase. Hexokinase catalyzes the phosphorylation of glucose to glucose-6-phosphate, an irreversible reaction under physiological conditions. Irreversible steps in glycolysis are key regulatory points that must be bypassed in gluconeogenesis to maintain metabolic balance. Answer is option a.
5) Guessed Question
A patient with alcohol intoxication is hypoglycemic. Which mechanism best explains this?
a) Increased gluconeogenesis
b) Inhibition of glycolysis
c) Increased NADH inhibits gluconeogenesis
d) Increased glycogen synthesis
Explanation: The correct answer is c) Increased NADH inhibits gluconeogenesis. Alcohol metabolism increases NADH/NAD+ ratio, diverting pyruvate to lactate and oxaloacetate to malate, preventing gluconeogenesis. This explains fasting hypoglycemia in alcoholics. Clinical management includes glucose supplementation and vitamin support. Answer is option c.
6) Guessed Question
Which enzyme connects gluconeogenesis and the urea cycle by generating fumarate?
a) Pyruvate carboxylase
b) PEP carboxykinase
c) Argininosuccinate lyase
d) Glucose-6-phosphatase
Explanation: The correct answer is c) Argininosuccinate lyase. This enzyme produces fumarate in the urea cycle, which enters gluconeogenesis via malate. Such metabolic interconnections integrate nitrogen and carbohydrate metabolism, essential for energy homeostasis and ammonia detoxification. Answer is option c.
7) Guessed Question
Which of the following steps is common to both glycolysis and gluconeogenesis?
a) Conversion of glucose to glucose-6-phosphate
b) Conversion of 1,3-BPG to 3-PG
c) Conversion of PEP to pyruvate
d) Conversion of fructose-6-phosphate to F-1,6-BP
Explanation: The correct answer is b) Conversion of 1,3-BPG to 3-PG. This reaction, catalyzed by phosphoglycerate kinase, is reversible and occurs in both glycolysis and gluconeogenesis. Shared steps conserve enzymes and resources, while bypass steps ensure directionality of pathways. Answer is option b.
8) Guessed Question
A neonate presents with severe lactic acidosis. Defect in which enzyme of gluconeogenesis is most likely?
a) Pyruvate carboxylase
b) Enolase
c) Aldolase
d) Triose phosphate isomerase
Explanation: The correct answer is a) Pyruvate carboxylase. Its deficiency leads to impaired conversion of pyruvate to oxaloacetate, blocking gluconeogenesis and causing lactic acidosis. Clinically, patients present with hypoglycemia, neurologic deficits, and failure to thrive. Treatment involves dietary modifications and supplements. Answer is option a.
9) Guessed Question
Which organ is the primary site of gluconeogenesis?
a) Muscle
b) Kidney
c) Liver
d) Adipose tissue
Explanation: The correct answer is c) Liver. The liver is the main site for gluconeogenesis, particularly during fasting. The kidney contributes during prolonged starvation. Other tissues lack the full complement of enzymes needed. This pathway maintains blood glucose homeostasis, crucial for brain and RBCs. Answer is option c.
10) Guessed Question
In uncontrolled diabetes, gluconeogenesis is stimulated mainly by which hormone?
a) Insulin
b) Glucagon
c) Epinephrine
d) Cortisol
Explanation: The correct answer is b) Glucagon. In diabetes, low insulin and high glucagon levels stimulate gluconeogenesis, worsening hyperglycemia. Glucagon activates key enzymes like PEP carboxykinase and fructose-1,6-bisphosphatase. This explains fasting hyperglycemia seen in type 1 diabetes mellitus. Answer is option b.
Topic: Carbohydrate Metabolism
Subtopic: Glycolysis
Keyword Definitions:
• Glycolysis: Pathway converting glucose to pyruvate with ATP production.
• Substrate level phosphorylation: Direct ATP generation from high-energy intermediates.
• Cancer cells: Depend on glycolysis (Warburg effect) for energy supply.
• NADPH: Reducing equivalent generated in pentose phosphate pathway, not glycolysis.
• Pyruvate kinase: Catalyzes final step of glycolysis, producing ATP.
• G3P dehydrogenase: Enzyme producing NADH during glycolysis.
• Two-carbon end product: Not true; glycolysis produces three-carbon pyruvate.
Lead Question - 2013
True about glycolysis are all except ?
a) Provide nutrition to cancer cells
b) Substrate level phosphorylation at pyruvate kinase
c) Two carbon end product is formed
d) NADPH is formed by glyceraldhyde-3-phosphate dehydrogenase
Explanation: The correct answer is d) NADPH is formed by glyceraldehyde-3-phosphate dehydrogenase. Glycolysis generates NADH, not NADPH. NADPH is produced in the pentose phosphate pathway. Glycolysis produces pyruvate (three-carbon), supports cancer metabolism, and includes substrate-level phosphorylation steps at phosphoglycerate kinase and pyruvate kinase. Thus, statement d is false. Answer is option d.
1) Guessed Question
Which glycolytic enzyme produces NADH?
a) Enolase
b) Aldolase
c) Glyceraldehyde-3-phosphate dehydrogenase
d) Pyruvate kinase
Explanation: The correct answer is c) Glyceraldehyde-3-phosphate dehydrogenase. This enzyme converts G3P to 1,3-bisphosphoglycerate, generating NADH. NADH later enters oxidative phosphorylation to produce ATP. Defects can impair glycolysis and energy yield. This makes G3P dehydrogenase a vital enzyme in energy metabolism. Answer is option c.
2) Guessed Question
A patient with pyruvate kinase deficiency will present with which clinical feature?
a) Hypoglycemia
b) Hemolytic anemia
c) Muscle weakness
d) Jaundice-free anemia
Explanation: The correct answer is b) Hemolytic anemia. Pyruvate kinase deficiency reduces ATP production in RBCs, impairing membrane stability, causing hemolysis. Clinically, patients show jaundice, splenomegaly, and anemia. Energy failure in RBCs explains the pathology. This condition is inherited and managed with supportive care. Answer is option b.
3) Guessed Question
Which step of glycolysis is inhibited by fluoride?
a) Pyruvate kinase
b) Enolase
c) Hexokinase
d) PFK-1
Explanation: The correct answer is b) Enolase. Fluoride inhibits enolase, preventing conversion of 2-phosphoglycerate to phosphoenolpyruvate. This is clinically significant for preserving blood glucose in fluoride tubes used for laboratory assays. Inhibition prevents glycolysis during sample storage. Answer is option b.
4) Guessed Question
Which glycolytic enzyme catalyzes an irreversible step?
a) Aldolase
b) Hexokinase
c) Phosphoglycerate kinase
d) Enolase
Explanation: The correct answer is b) Hexokinase. Hexokinase catalyzes the phosphorylation of glucose to glucose-6-phosphate, an irreversible step under cellular conditions. Such irreversible steps are key control points in glycolysis and must be bypassed in gluconeogenesis. Answer is option b.
5) Guessed Question
A neonate with severe lactic acidosis likely has a deficiency of which enzyme?
a) Pyruvate dehydrogenase
b) Enolase
c) Hexokinase
d) Triose phosphate isomerase
Explanation: The correct answer is a) Pyruvate dehydrogenase. Deficiency blocks conversion of pyruvate to acetyl-CoA, leading to lactic acidosis. Patients present with neurologic deficits, hypotonia, and developmental delay. Clinical management includes ketogenic diet to bypass glycolysis. Answer is option a.
6) Guessed Question
Which step of glycolysis directly generates ATP?
a) Pyruvate kinase
b) Enolase
c) Aldolase
d) Hexokinase
Explanation: The correct answer is a) Pyruvate kinase. Pyruvate kinase catalyzes substrate-level phosphorylation, producing ATP when phosphoenolpyruvate is converted to pyruvate. This is one of two ATP-generating steps in glycolysis, the other being phosphoglycerate kinase. This explains net ATP gain. Answer is option a.
7) Guessed Question
A patient on isoniazid therapy develops pellagra-like symptoms due to deficiency of which glycolytic cofactor?
a) Niacin
b) Riboflavin
c) Thiamine
d) Pyridoxine
Explanation: The correct answer is a) Niacin. Niacin deficiency reduces NAD+ availability, impairing glyceraldehyde-3-phosphate dehydrogenase activity in glycolysis. Clinically, pellagra manifests with diarrhea, dermatitis, and dementia. Isoniazid interferes with vitamin metabolism, aggravating deficiency. Answer is option a.
8) Guessed Question
Which glycolytic enzyme defect leads to hereditary hemolytic anemia other than pyruvate kinase deficiency?
a) Hexokinase
b) Phosphoglycerate kinase
c) PFK-1
d) Aldolase
Explanation: The correct answer is a) Hexokinase. Hexokinase deficiency decreases glycolytic ATP production in RBCs, causing hereditary hemolytic anemia. Clinical features include anemia, jaundice, and splenomegaly. Such enzyme deficiencies impair RBC survival due to their dependence on glycolysis for energy. Answer is option a.
9) Guessed Question
Which tissue relies exclusively on glycolysis for ATP generation?
a) Brain
b) Red blood cells
c) Heart
d) Liver
Explanation: The correct answer is b) Red blood cells. RBCs lack mitochondria, relying solely on glycolysis for ATP. This dependence explains their vulnerability to glycolytic enzyme defects. Brain also uses glycolysis but relies heavily on oxidative phosphorylation. RBCs are unique in complete glycolytic dependence. Answer is option b.
10) Guessed Question
A patient with sepsis develops high lactate levels. This is due to?
a) Increased aerobic glycolysis
b) Decreased oxygen supply causing anaerobic glycolysis
c) Increased gluconeogenesis
d) Inhibition of hexokinase
Explanation: The correct answer is b) Decreased oxygen supply causing anaerobic glycolysis. In sepsis, hypoperfusion and hypoxia stimulate anaerobic glycolysis, leading to lactate accumulation. Clinically, lactic acidosis is a poor prognostic sign in septic shock. Management requires oxygenation and hemodynamic support. Answer is option b.
Topic: Carbohydrate Metabolism
Subtopic: Anaerobic Glycolysis
Keyword Definitions:
• Anaerobic glycolysis: Glucose breakdown without oxygen, producing lactate.
• RBCs: Lack mitochondria; depend entirely on anaerobic glycolysis for ATP.
• Muscles: Use anaerobic glycolysis during intense exercise when oxygen is limited.
• Brain: Primarily aerobic; anaerobic glycolysis not physiologically significant.
• Kidney: Utilizes aerobic glycolysis and oxidative phosphorylation.
• Lactate: End product of anaerobic glycolysis in humans.
• ATP: Cellular energy generated from glycolysis and oxidative pathways.
Lead Question - 2013
Anaerobic glycolysis occurs in all places except
a) Muscles
b) RBCs
c) Brain
d) Kidney
Explanation: The correct answer is d) Kidney. Anaerobic glycolysis occurs in tissues lacking sufficient oxygen or mitochondria, such as RBCs and exercising muscle. The brain mainly relies on aerobic metabolism. Kidney is primarily aerobic and does not significantly use anaerobic glycolysis. Thus, kidney is the exception. Answer is option d.
1) Guessed Question
Which is the main end product of anaerobic glycolysis in humans?
a) Ethanol
b) Lactate
c) Acetyl-CoA
d) Pyruvate
Explanation: The correct answer is b) Lactate. In anaerobic glycolysis, pyruvate is reduced to lactate by lactate dehydrogenase, regenerating NAD+ for glycolysis continuation. This process sustains ATP production in oxygen-poor conditions. Unlike yeast producing ethanol, humans generate lactate under anaerobic conditions. Answer is option b.
2) Guessed Question
A marathon runner develops muscle cramps due to anaerobic glycolysis. Which metabolite accumulates?
a) Lactate
b) Citrate
c) Acetyl-CoA
d) Oxaloacetate
Explanation: The correct answer is a) Lactate. During intense exercise, oxygen supply is insufficient, leading to anaerobic glycolysis. Lactate accumulates, lowering pH and causing muscle cramps and fatigue. This reversible process is relieved after rest and oxygen supply restoration. Answer is option a.
3) Guessed Question
Which enzyme catalyzes the conversion of pyruvate to lactate?
a) Pyruvate dehydrogenase
b) Lactate dehydrogenase
c) Pyruvate carboxylase
d) Malate dehydrogenase
Explanation: The correct answer is b) Lactate dehydrogenase. This enzyme reduces pyruvate to lactate, regenerating NAD+ needed for glycolysis. It is essential in anaerobic metabolism, especially in tissues like RBCs and exercising muscles. Elevated lactate dehydrogenase levels indicate tissue injury or hemolysis clinically. Answer is option b.
4) Guessed Question
Which tissue relies exclusively on anaerobic glycolysis for ATP?
a) Liver
b) Kidney
c) RBCs
d) Brain
Explanation: The correct answer is c) RBCs. Red blood cells lack mitochondria, hence cannot perform aerobic metabolism. They depend completely on anaerobic glycolysis for ATP generation. This makes glycolysis essential for RBC survival and function. Deficiency of glycolytic enzymes causes hemolytic anemia. Answer is option c.
5) Guessed Question
A patient in septic shock develops high blood lactate. The cause is:
a) Enhanced gluconeogenesis
b) Anaerobic glycolysis due to tissue hypoxia
c) Increased glycogenolysis
d) Inhibition of oxidative phosphorylation
Explanation: The correct answer is b) Anaerobic glycolysis due to tissue hypoxia. In septic shock, poor perfusion and hypoxia shift metabolism to anaerobic glycolysis, producing excess lactate and causing lactic acidosis. Elevated lactate is a marker of severity and poor prognosis. Answer is option b.
6) Guessed Question
Which organ clears most of the lactate produced by anaerobic glycolysis?
a) Heart
b) Brain
c) Liver
d) Kidney
Explanation: The correct answer is c) Liver. Lactate is transported to the liver and converted back to glucose via gluconeogenesis in the Cori cycle. This maintains glucose homeostasis and prevents severe lactic acidosis. The liver’s metabolic role is essential in clearing lactate from circulation. Answer is option c.
7) Guessed Question
A newborn presents with persistent lactic acidosis and developmental delay. Which enzyme deficiency is most likely?
a) Pyruvate carboxylase
b) Lactate dehydrogenase
c) Hexokinase
d) Enolase
Explanation: The correct answer is a) Pyruvate carboxylase. Deficiency blocks conversion of pyruvate to oxaloacetate, shunting pyruvate to lactate and causing lactic acidosis. Clinical features include neurologic impairment and failure to thrive. Dietary modifications and supportive therapy are management approaches. Answer is option a.
8) Guessed Question
Which laboratory test uses fluoride to inhibit anaerobic glycolysis in blood samples?
a) Urea test
b) Glucose estimation
c) Serum creatinine
d) Bilirubin levels
Explanation: The correct answer is b) Glucose estimation. Sodium fluoride inhibits enolase, preventing glycolysis in collected blood samples. This stabilizes glucose levels for accurate laboratory testing. Without inhibition, glycolysis would artificially lower glucose concentration during storage. Answer is option b.
9) Guessed Question
In ischemic heart tissue, anaerobic glycolysis leads to accumulation of which metabolite?
a) Acetyl-CoA
b) Lactate
c) Succinyl-CoA
d) Oxaloacetate
Explanation: The correct answer is b) Lactate. In ischemia, oxygen deficiency forces cardiac cells to depend on anaerobic glycolysis, producing lactate. This causes intracellular acidosis and contributes to myocardial injury. Clinical findings include elevated serum lactate in ischemic conditions. Answer is option b.
10) Guessed Question
Which condition shows increased anaerobic glycolysis even in presence of oxygen (Warburg effect)?
a) Diabetes mellitus
b) Cancer
c) Starvation
d) Hypothyroidism
Explanation: The correct answer is b) Cancer. Tumor cells preferentially use anaerobic glycolysis even with adequate oxygen, a phenomenon called the Warburg effect. This supports rapid proliferation and survival in hypoxic tumor microenvironments. It also forms the basis for PET imaging using glucose analogs. Answer is option b.
Topic: Carbohydrate Metabolism
Subtopic: Krebs Cycle (TCA Cycle)
Keyword Definitions:
• Krebs Cycle: Central aerobic pathway oxidizing acetyl-CoA to CO₂.
• ATP: Main cellular energy molecule generated in metabolism.
• NADH: Reduced coenzyme yielding ATP via oxidative phosphorylation.
• FADH₂: Reduced coenzyme yielding ATP through electron transport chain.
• Substrate level phosphorylation: Direct ATP or GTP generation in cycle.
• Oxidative phosphorylation: ATP synthesis using mitochondrial electron transport chain.
• Succinate dehydrogenase: Enzyme producing FADH₂ in Krebs cycle.
Lead Question - 2013
The number of ATPs generated in krebs cycle are ?
a) 12
b) 24
c) 15
d) 30
Explanation: The correct answer is a) 12. One turn of the Krebs cycle generates 3 NADH, 1 FADH₂, and 1 GTP. This corresponds to 9 ATP from NADH, 2 ATP from FADH₂, and 1 ATP from GTP, totaling 12 ATP equivalents per cycle. Answer is option a.
1) Guessed Question
Which enzyme of the Krebs cycle produces GTP directly?
a) Citrate synthase
b) Succinate thiokinase
c) Isocitrate dehydrogenase
d) Fumarase
Explanation: The correct answer is b) Succinate thiokinase. Also known as succinyl-CoA synthetase, this enzyme catalyzes substrate-level phosphorylation, producing GTP from GDP. This is the only step in the cycle generating ATP/GTP directly without oxidative phosphorylation. Answer is option b.
2) Guessed Question
A patient with thiamine deficiency has impaired Krebs cycle at which enzyme?
a) Succinate dehydrogenase
b) α-Ketoglutarate dehydrogenase
c) Fumarase
d) Malate dehydrogenase
Explanation: The correct answer is b) α-Ketoglutarate dehydrogenase. Thiamine (Vitamin B1) is a cofactor for α-ketoglutarate dehydrogenase. Its deficiency impairs ATP generation and causes lactic acidosis. Clinically, it presents as Beriberi and Wernicke-Korsakoff syndrome. Answer is option b.
3) Guessed Question
Which is the only enzyme of Krebs cycle embedded in the inner mitochondrial membrane?
a) Malate dehydrogenase
b) Succinate dehydrogenase
c) Aconitase
d) Isocitrate dehydrogenase
Explanation: The correct answer is b) Succinate dehydrogenase. This enzyme catalyzes the conversion of succinate to fumarate, producing FADH₂. It is unique because it is part of both the Krebs cycle and electron transport chain (Complex II). Answer is option b.
4) Guessed Question
How many NADH molecules are produced per acetyl-CoA in Krebs cycle?
a) 2
b) 3
c) 4
d) 1
Explanation: The correct answer is b) 3. Each acetyl-CoA oxidation in the Krebs cycle yields 3 NADH molecules through isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate dehydrogenase steps. These NADH molecules generate 9 ATP via oxidative phosphorylation. Answer is option b.
5) Guessed Question
A patient with fumarase deficiency would show accumulation of which metabolite?
a) Succinate
b) Fumarate
c) Malate
d) Citrate
Explanation: The correct answer is b) Fumarate. Fumarase catalyzes the hydration of fumarate to malate. Deficiency leads to fumarate accumulation and impaired ATP generation. Clinically, this rare condition presents with encephalopathy, seizures, and developmental delay. Answer is option b.
6) Guessed Question
Which cofactor is required by succinate dehydrogenase?
a) Biotin
b) FAD
c) NAD+
d) Coenzyme A
Explanation: The correct answer is b) FAD. Succinate dehydrogenase requires flavin adenine dinucleotide (FAD) as a cofactor, producing FADH₂ when succinate is converted to fumarate. FAD is derived from riboflavin (Vitamin B2). Riboflavin deficiency impairs this step. Answer is option b.
7) Guessed Question
In myocardial ischemia, Krebs cycle activity decreases due to deficiency of?
a) Oxygen
b) Glucose
c) FADH₂
d) Acetyl-CoA
Explanation: The correct answer is a) Oxygen. Oxygen is the final electron acceptor in oxidative phosphorylation. In ischemia, lack of oxygen halts electron transport, reducing NAD+ and FAD availability, thereby inhibiting the Krebs cycle. This results in lactate accumulation and energy deficit. Answer is option a.
8) Guessed Question
How many FADH₂ molecules are generated in one turn of the Krebs cycle?
a) 1
b) 2
c) 3
d) 4
Explanation: The correct answer is a) 1. Succinate dehydrogenase produces 1 FADH₂ per acetyl-CoA oxidized in the Krebs cycle. This corresponds to 2 ATP equivalents through oxidative phosphorylation. Answer is option a.
9) Guessed Question
A patient with mitochondrial malate dehydrogenase defect would show impaired production of?
a) NADH
b) FADH₂
c) GTP
d) Acetyl-CoA
Explanation: The correct answer is a) NADH. Malate dehydrogenase converts malate to oxaloacetate, generating NADH. A defect decreases NADH production and ATP yield, impairing Krebs cycle progression. Clinically, energy deficiency leads to muscle weakness and neurologic symptoms. Answer is option a.
10) Guessed Question
Which of the following links glycolysis with the Krebs cycle?
a) Acetyl-CoA
b) Fumarate
c) Oxaloacetate
d) GTP
Explanation: The correct answer is a) Acetyl-CoA. Pyruvate from glycolysis is converted into acetyl-CoA by pyruvate dehydrogenase. Acetyl-CoA then enters the Krebs cycle. This step is essential for carbohydrate oxidation under aerobic conditions, linking glycolysis and the Krebs cycle. Answer is option a.
Topic: Carbohydrate Metabolism
Subtopic: Krebs Cycle (TCA Cycle)
Keyword Definitions:
• Krebs Cycle: Aerobic pathway oxidizing acetyl-CoA to CO₂ and energy.
• ATP: Universal cellular energy currency generated in metabolism.
• NADH: Reduced coenzyme yielding ATP through oxidative phosphorylation.
• FADH₂: Reduced flavoprotein coenzyme producing ATP via electron transport.
• GTP: Energy molecule produced by substrate-level phosphorylation.
• Oxaloacetate: Final product regenerating the cycle.
• Substrate level phosphorylation: Direct ATP/GTP synthesis in metabolic cycles.
Lead Question - 2013
One Krebs cycle generates how many ATP ?
a) 6
b) 12
c) 24
d) 36
Explanation: The correct answer is b) 12. A single turn of the Krebs cycle produces 3 NADH, 1 FADH₂, and 1 GTP. Through oxidative phosphorylation, this yields 9 ATP from NADH, 2 ATP from FADH₂, and 1 ATP from GTP. The total is 12 ATP. Answer is option b.
1) Guessed Question
Which Krebs cycle enzyme produces GTP directly?
a) Succinate thiokinase
b) Malate dehydrogenase
c) Aconitase
d) Citrate synthase
Explanation: The correct answer is a) Succinate thiokinase. Also called succinyl-CoA synthetase, this enzyme catalyzes the substrate-level phosphorylation step, forming GTP from GDP. This is the only direct energy-producing step in the Krebs cycle without electron transport. Thus, the answer is option a.
2) Guessed Question
In thiamine deficiency, which Krebs cycle enzyme activity decreases?
a) α-Ketoglutarate dehydrogenase
b) Succinate dehydrogenase
c) Malate dehydrogenase
d) Isocitrate dehydrogenase
Explanation: The correct answer is a) α-Ketoglutarate dehydrogenase. This enzyme requires thiamine pyrophosphate as a cofactor. Deficiency leads to impaired ATP production, accumulation of α-ketoglutarate, and lactic acidosis. It is implicated in diseases like beriberi and Wernicke-Korsakoff syndrome. Answer is option a.
3) Guessed Question
How many NADH molecules are formed per cycle of Krebs cycle?
a) 2
b) 3
c) 4
d) 1
Explanation: The correct answer is b) 3. Three NADH molecules are produced in the Krebs cycle by isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate dehydrogenase reactions. Each NADH contributes 3 ATP, totaling 9 ATP from these steps. Answer is option b.
4) Guessed Question
A newborn with fumarase deficiency will accumulate which metabolite?
a) Malate
b) Succinate
c) Fumarate
d) Citrate
Explanation: The correct answer is c) Fumarate. Fumarase normally hydrates fumarate to malate. Deficiency causes fumarate accumulation, impaired energy generation, and neurologic symptoms like seizures and developmental delay. It is a rare autosomal recessive condition. Answer is option c.
5) Guessed Question
Which enzyme links the Krebs cycle and the electron transport chain?
a) Succinate dehydrogenase
b) Citrate synthase
c) Malate dehydrogenase
d) Aconitase
Explanation: The correct answer is a) Succinate dehydrogenase. This unique enzyme is located in the inner mitochondrial membrane and is also Complex II of the electron transport chain. It catalyzes conversion of succinate to fumarate, producing FADH₂. Answer is option a.
6) Guessed Question
A patient with myocardial infarction has reduced ATP due to impaired?
a) Oxygen supply
b) Acetyl-CoA supply
c) NADH supply
d) GTP supply
Explanation: The correct answer is a) Oxygen supply. Oxygen is the final electron acceptor in the electron transport chain. Lack of oxygen halts oxidative phosphorylation, reduces NAD+ and FAD regeneration, and inhibits Krebs cycle, causing energy failure in ischemic tissues. Answer is option a.
7) Guessed Question
How many FADH₂ molecules are produced per acetyl-CoA in Krebs cycle?
a) 1
b) 2
c) 3
d) 4
Explanation: The correct answer is a) 1. Succinate dehydrogenase catalyzes the oxidation of succinate to fumarate, producing one FADH₂ per acetyl-CoA. This FADH₂ generates 2 ATP through oxidative phosphorylation. Answer is option a.
8) Guessed Question
In pyruvate dehydrogenase deficiency, which substrate accumulates?
a) Pyruvate
b) Acetyl-CoA
c) Fumarate
d) Oxaloacetate
Explanation: The correct answer is a) Pyruvate. Pyruvate dehydrogenase converts pyruvate into acetyl-CoA. Deficiency results in pyruvate accumulation, which is shunted to lactate, causing lactic acidosis and neurologic symptoms. This enzyme links glycolysis and Krebs cycle. Answer is option a.
9) Guessed Question
Which is the final product of Krebs cycle before regeneration?
a) Malate
b) Citrate
c) Oxaloacetate
d) Succinate
Explanation: The correct answer is c) Oxaloacetate. The cycle begins with acetyl-CoA combining with oxaloacetate to form citrate, and ends with regeneration of oxaloacetate from malate. This ensures continuous cycling. Answer is option c.
10) Guessed Question
A patient with riboflavin deficiency will have reduced activity of which enzyme?
a) Succinate dehydrogenase
b) Malate dehydrogenase
c) Isocitrate dehydrogenase
d) Citrate synthase
Explanation: The correct answer is a) Succinate dehydrogenase. Riboflavin (Vitamin B2) is a precursor of FAD, required by succinate dehydrogenase. Deficiency leads to reduced FADH₂ production and decreased ATP yield, impairing energy metabolism. Answer is option a.
Topic: Carbohydrate Metabolism
Subtopic: TCA Cycle (Krebs Cycle) Cofactors
Keyword Definitions:
• TCA Cycle: Tricarboxylic acid cycle oxidizing acetyl-CoA to CO₂ and energy.
• Niacin: Vitamin B3, precursor of NAD⁺ required for dehydrogenase reactions.
• Riboflavin: Vitamin B2, precursor of FAD used by succinate dehydrogenase.
• Thiamine: Vitamin B1, cofactor for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase.
• Folic acid: Vitamin B9, required for one-carbon metabolism, not directly in TCA.
• NAD⁺: Oxidized coenzyme accepting electrons in TCA.
• FAD: Oxidized flavoprotein accepting electrons in TCA.
Lead Question - 2013
Vitamin not required in TCA cycle ?
a) Niacin
b) Riboflavin
c) Thiamine
d) Folic acid
Explanation: The correct answer is d) Folic acid. Niacin (NAD⁺), riboflavin (FAD), and thiamine (TPP) are essential cofactors for dehydrogenases in the TCA cycle. Folic acid is involved in one-carbon metabolism and not directly required for TCA cycle reactions. Therefore, the vitamin not needed is folic acid. Answer is option d.
1) Guessed Question
Which TCA cycle enzyme requires thiamine pyrophosphate as a cofactor?
a) Citrate synthase
b) α-Ketoglutarate dehydrogenase
c) Succinate dehydrogenase
d) Malate dehydrogenase
Explanation: The correct answer is b) α-Ketoglutarate dehydrogenase. Thiamine pyrophosphate is essential for decarboxylation of α-ketoglutarate to succinyl-CoA. Deficiency leads to impaired ATP production and accumulation of upstream metabolites, causing lactic acidosis. Clinical manifestations include Wernicke-Korsakoff syndrome and beriberi. Answer is option b.
2) Guessed Question
Which vitamin forms the coenzyme FAD used in TCA cycle?
a) Niacin
b) Riboflavin
c) Thiamine
d) Pantothenic acid
Explanation: The correct answer is b) Riboflavin. Riboflavin (Vitamin B2) is converted into FAD, which acts as an electron acceptor in succinate dehydrogenase reaction. FAD is essential for electron transport and ATP generation. Riboflavin deficiency impairs energy metabolism. Answer is option b.
3) Guessed Question
A patient with niacin deficiency will have decreased activity of which coenzyme in TCA cycle?
a) NAD⁺
b) FAD
c) CoA
d) TPP
Explanation: The correct answer is a) NAD⁺. Niacin is the precursor of NAD⁺, required for several dehydrogenase reactions in TCA cycle, including isocitrate, α-ketoglutarate, and malate dehydrogenase. NAD⁺ deficiency reduces ATP generation and energy production. Answer is option a.
4) Guessed Question
Which cofactor links glycolysis to TCA cycle via pyruvate dehydrogenase?
a) NAD⁺
b) TPP (Thiamine pyrophosphate)
c) FAD
d) Biotin
Explanation: The correct answer is b) TPP (Thiamine pyrophosphate). TPP is a cofactor for pyruvate dehydrogenase converting pyruvate to acetyl-CoA, linking glycolysis to TCA. Deficiency leads to energy depletion, accumulation of pyruvate, and lactic acidosis. Answer is option b.
5) Guessed Question
Which coenzyme is produced from niacin and participates in electron transfer in TCA cycle?
a) NAD⁺
b) FAD
c) CoA
d) GTP
Explanation: The correct answer is a) NAD⁺. Niacin-derived NAD⁺ acts as an electron acceptor in dehydrogenase reactions of TCA cycle. It generates NADH, which donates electrons to the electron transport chain for ATP synthesis. Niacin deficiency reduces NADH and ATP production. Answer is option a.
6) Guessed Question
A patient presents with Wernicke’s encephalopathy. Which TCA enzyme is affected?
a) Isocitrate dehydrogenase
b) α-Ketoglutarate dehydrogenase
c) Fumarase
d) Malate dehydrogenase
Explanation: The correct answer is b) α-Ketoglutarate dehydrogenase. Thiamine deficiency impairs α-ketoglutarate dehydrogenase, reducing ATP production in brain tissue. This contributes to neurological symptoms such as ophthalmoplegia, ataxia, and confusion, characteristic of Wernicke’s encephalopathy. Answer is option b.
7) Guessed Question
Which TCA cycle enzyme uses FAD as a cofactor?
a) Citrate synthase
b) Succinate dehydrogenase
c) α-Ketoglutarate dehydrogenase
d) Malate dehydrogenase
Explanation: The correct answer is b) Succinate dehydrogenase. FAD is required to oxidize succinate to fumarate, producing FADH₂. This reaction is linked to the electron transport chain for ATP generation. Riboflavin deficiency impairs FAD synthesis, reducing ATP production. Answer is option b.
8) Guessed Question
Which vitamin is NOT a direct cofactor in TCA cycle reactions?
a) Niacin
b) Riboflavin
c) Thiamine
d) Vitamin C
Explanation: The correct answer is d) Vitamin C. Vitamin C is an antioxidant but is not directly involved as a cofactor in TCA cycle enzyme reactions. Niacin, riboflavin, and thiamine are all essential cofactors for dehydrogenases and decarboxylases in the cycle. Answer is option d.
9) Guessed Question
Which vitamin deficiency impairs conversion of pyruvate to acetyl-CoA?
a) Riboflavin
b) Thiamine
c) Niacin
d) Pantothenic acid
Explanation: The correct answer is b) Thiamine. Thiamine pyrophosphate is required by pyruvate dehydrogenase. Deficiency results in pyruvate accumulation and lactic acidosis. This links carbohydrate metabolism to the TCA cycle, and deficiency impairs energy production. Answer is option b.
10) Guessed Question
Which vitamin contributes to formation of coenzyme A, essential for TCA cycle entry?
a) Pantothenic acid
b) Thiamine
c) Riboflavin
d) Niacin
Explanation: The correct answer is a) Pantothenic acid. Pantothenic acid is a component of coenzyme A, which forms acetyl-CoA entering the TCA cycle. Its deficiency impairs energy metabolism by reducing substrate availability. Answer is option a.
Topic: Carbohydrate Metabolism
Subtopic: Glycogenesis
Keyword Definitions:
• Glycogenesis: Process of synthesizing glycogen from glucose.
• UTP: Uridine triphosphate, energy donor for glycogen synthesis.
• GTP: Guanosine triphosphate, energy molecule not primarily used in glycogenesis.
• UDP-glucose: Activated glucose donor formed using UTP.
• Glycogen synthase: Enzyme catalyzing elongation of glycogen chain.
• Energy currency: Molecules like ATP, GTP, UTP providing energy for biosynthesis.
• UDP: Uridine diphosphate, formed after UTP donates energy in glycogenesis.
Lead Question - 2013
The energy for glycogenesis is provided by -
a) GTP
b) GDP
c) UTP
d) AMP
Explanation: The correct answer is c) UTP. Glycogenesis requires UTP to form UDP-glucose, which donates glucose units to glycogen chains. UTP acts as the energy source enabling the enzymatic addition of glucose to glycogen. GTP, GDP, and AMP are not used directly in glycogen synthesis. Answer is option c.
1) Guessed Question
Which enzyme converts glucose-1-phosphate to UDP-glucose?
a) Glycogen synthase
b) UDP-glucose pyrophosphorylase
c) Phosphoglucomutase
d) Glycogen phosphorylase
Explanation: The correct answer is b) UDP-glucose pyrophosphorylase. This enzyme activates glucose-1-phosphate using UTP to form UDP-glucose, the immediate glucose donor for glycogen elongation. This step is essential for glycogen synthesis. Answer is option b.
2) Guessed Question
Which enzyme elongates the glycogen chain?
a) Glycogen synthase
b) Branching enzyme
c) Phosphoglucomutase
d) Glucose-6-phosphatase
Explanation: The correct answer is a) Glycogen synthase. Glycogen synthase adds glucose units from UDP-glucose to the growing glycogen chain via α-1,4-glycosidic bonds. It is the key regulatory enzyme in glycogenesis. Branching enzyme introduces α-1,6 branches. Answer is option a.
3) Guessed Question
Which energy molecule is hydrolyzed to form UDP-glucose?
a) ATP
b) UTP
c) GTP
d) ADP
Explanation: The correct answer is b) UTP. UTP combines with glucose-1-phosphate to form UDP-glucose, releasing pyrophosphate. This reaction provides the energy needed to activate glucose for incorporation into glycogen. ATP or GTP are not used directly in this step. Answer is option b.
4) Guessed Question
Which enzyme introduces α-1,6 branch points in glycogen?
a) Branching enzyme
b) Glycogen synthase
c) Debranching enzyme
d) Phosphoglucomutase
Explanation: The correct answer is a) Branching enzyme. It transfers a segment of α-1,4-linked glucoses to create α-1,6 branches, increasing solubility and accessibility for glycogen phosphorylase. This branching is essential for efficient glycogen metabolism. Answer is option a.
5) Guessed Question
In liver, glycogenesis is stimulated by which hormone?
a) Glucagon
b) Insulin
c) Epinephrine
d) Cortisol
Explanation: The correct answer is b) Insulin. Insulin activates glycogen synthase and inhibits glycogen phosphorylase, promoting glycogen storage in liver and muscle. Glucagon and epinephrine stimulate glycogenolysis. Insulin signaling ensures glucose is stored during fed state. Answer is option b.
6) Guessed Question
A patient with glycogen storage disease type 0 has deficiency of which enzyme?
a) Glycogen synthase
b) Branching enzyme
c) Debranching enzyme
d) Phosphoglucomutase
Explanation: The correct answer is a) Glycogen synthase. Type 0 disease is caused by deficiency of glycogen synthase, resulting in impaired glycogen storage, fasting hypoglycemia, and postprandial hyperglycemia. Energy storage is compromised. Answer is option a.
7) Guessed Question
Which cofactor is required for glycogen phosphorylase activity during glycogenolysis?
a) Pyridoxal phosphate (Vitamin B6)
b) TPP
c) NAD⁺
d) FAD
Explanation: The correct answer is a) Pyridoxal phosphate (Vitamin B6). Pyridoxal phosphate acts as a coenzyme for glycogen phosphorylase, enabling cleavage of α-1,4 glycosidic bonds to release glucose-1-phosphate during glycogen breakdown. Answer is option a.
8) Guessed Question
Which molecule is immediate glucose donor for glycogen synthesis?
a) Glucose-6-phosphate
b) UDP-glucose
c) Glucose-1-phosphate
d) ATP
Explanation: The correct answer is b) UDP-glucose. UDP-glucose is formed from glucose-1-phosphate and UTP. Glycogen synthase uses UDP-glucose to elongate glycogen chains, making it the immediate donor of glucose residues. Answer is option b.
9) Guessed Question
Which hormone inhibits glycogenesis in muscle?
a) Glucagon
b) Epinephrine
c) Insulin
d) Growth hormone
Explanation: The correct answer is b) Epinephrine. Epinephrine activates glycogen phosphorylase via cAMP-mediated phosphorylation, inhibiting glycogen synthase and halting glycogenesis. This ensures glucose mobilization during stress or exercise. Insulin promotes glycogenesis. Answer is option b.
10) Guessed Question
Which enzyme converts glucose-6-phosphate to glucose-1-phosphate in glycogenesis?
a) Phosphoglucomutase
b) Glycogen synthase
c) Branching enzyme
d) Hexokinase
Explanation: The correct answer is a) Phosphoglucomutase. Phosphoglucomutase converts glucose-6-phosphate to glucose-1-phosphate, which is then activated by UTP to form UDP-glucose for glycogen synthesis. This is an essential preparatory step in glycogenesis. Answer is option a.