Topic: Electron Transport Chain & Uncouplers
Subtopic: Uncoupling Agents & Oxidative Phosphorylation
Keyword Definitions:
• Uncoupler: A molecule that dissipates the proton gradient across the inner mitochondrial membrane, producing heat instead of ATP.
• Thermogenin (UCP1): Natural uncoupling protein located in brown adipose tissue generating heat (non-shivering thermogenesis).
• 2,4-Dinitrophenol (DNP): A chemical protonophore uncoupler that increases metabolic rate and produces heat.
• Oligomycin: An inhibitor of ATP synthase (FoF1), blocking proton flow and ATP production.
• Oxidative phosphorylation: ATP generation driven by electron transport and proton-motive force across the inner mitochondrial membrane.
Lead Question - 2013
Natural uncoupler is ?
a) Thermogonin
b) 2, 4 nitrophenol
c) 2, 4 Dinitrophenol
d) Oligomycin
Answer & Explanation:
Thermogenin is the natural mitochondrial uncoupler in brown adipose tissue that dissipates the proton gradient and generates heat instead of ATP. Chemical uncouplers like 2,4-dinitrophenol are synthetic, and oligomycin inhibits ATP synthase. Correct answer is a) Thermogonin. This thermogenic mechanism is vital for neonatal and cold adaptation in mammalian physiology.
1) 2,4-Dinitrophenol acts by ?
a) Inhibiting ATP synthase
b) Increasing proton conductance
c) Blocking Complex IV
d) Inhibiting glycolysis
Explanation:
2,4-Dinitrophenol acts as a protonophore, increasing proton conductance across the inner mitochondrial membrane and collapsing the proton gradient. This uncouples electron transport from ATP synthesis, increasing oxygen consumption and heat production while decreasing ATP yield. Therefore, the correct answer is b) Increasing proton conductance, causing heat production and energy wastage.
2) Which protein is the natural uncoupler in brown adipose tissue?
a) Thermogenin
b) ATP synthase
c) Cytochrome c
d) Ferritin
Explanation:
Thermogenin, also called uncoupling protein UCP1, is embedded in the inner mitochondrial membrane of brown adipose tissue. It dissipates the proton gradient to produce heat, contributing to non-shivering thermogenesis. This natural uncoupler's physiological role is adaptive thermoregulation. Correct answer is a) Thermogenin, critical for neonatal survival during acute cold exposure.
3) 2,4-Dinitrophenol was historically used for ?
a) Antioxidant therapy
b) Antipyretic medication
c) Weight loss by increasing metabolic rate
d) Antibacterial agent
Explanation:
2,4-Dinitrophenol is a chemical uncoupler historically used for weight loss by increasing metabolic rate. It transports protons across mitochondrial membranes, collapsing proton motive force, generating heat instead of ATP, and causing hyperthermia and fatal toxicity at high doses. Correct answer is c) 2,4 Dinitrophenol, leading to dangerous metabolic derangements often.
4) Oligomycin inhibits ATP synthesis by binding to ?
a) Fo subunit of ATP synthase
b) F1 catalytic subunit
c) Complex IV
d) Complex I
Explanation:
Oligomycin binds to the Fo subunit of ATP synthase, blocking proton channel and preventing proton flow through ATP synthase. This inhibits ATP synthesis despite intact electron transport, leading to reduced ATP levels and increased proton gradient. Therefore, oligomycin’s mechanism is Fo subunit inhibition; correct answer is a) Fo subunit activity.
5) Uncouplers affect oxygen consumption by ?
a) Increasing oxygen consumption
b) Decreasing oxygen consumption
c) No change in oxygen consumption
d) Variable effect only in liver
Explanation:
Uncouplers increase oxygen consumption because electron transport accelerates to restore the dissipated proton gradient, but ATP synthesis falls. Cells consume more oxygen and substrates while producing heat. Clinically, this causes hyperthermia and increased metabolic rate. Therefore, the correct answer is a) Increase in oxygen consumption and decreased ATP yield consequently.
6) DNP (2,4-dinitrophenol) overdose typically causes ?
a) Hyperthermia and systemic toxicity
b) Hypothermia and bradycardia
c) Hypoglycemia only
d) Renal colic
Explanation:
Dinitrophenol overdose uncouples oxidative phosphorylation, causing uncontrolled heat production, hyperthermia, tachycardia, diaphoresis, metabolic acidosis, and potentially fatal multiorgan failure. Treatment is supportive with cooling and symptomatic care; no specific antidote exists. Correct answer is a) Hyperthermia and related systemic toxicity following DNP poisoning requiring intensive supportive care in hospital settings.
7) Uncouplers cause which change in ATP and heat production?
a) Increased ATP and decreased heat
b) Decreased ATP and increased heat
c) Increased both ATP and heat
d) No change in either
Explanation:
Uncouplers decrease ATP production while increasing heat generation because they dissipate the proton gradient, preventing ATP synthase from harnessing proton-motive force. The energy from substrate oxidation is released as heat. Clinically, this shifts cellular metabolism toward increased substrate consumption and thermogenesis. Correct answer is b) Decreased ATP and increased heat.
8) Which compound is a specific inhibitor of Complex I?
a) Antimycin A
b) Cyanide
c) Rotenone
d) Oligomycin
Explanation:
Rotenone is a plant-derived inhibitor of mitochondrial Complex I (NADH dehydrogenase), blocking electron transfer to coenzyme Q. This inhibition reduces proton pumping, collapses ATP synthesis, and increases reactive oxygen species. Rotenone exposure causes neurotoxicity and experimental Parkinsonism. Correct answer is c) Rotenone, a Complex I inhibitor used in experimental neurotoxicology studies.
9) Which of the following is NOT an uncoupler?
a) 2,4-Dinitrophenol
b) Thermogenin (UCP1)
c) Carbonyl cyanide m-chlorophenyl hydrazone (CCCP)
d) Oligomycin
Explanation:
Oligomycin is not an uncoupler; it inhibits ATP synthase by blocking Fo proton channel, preventing proton flow and ATP production. Uncouplers instead increase proton permeability, collapsing the gradient and producing heat. Therefore, oligomycin reduces ATP synthesis without increasing oxygen consumption as classical uncouplers do. Correct answer is d) Oligomycin here.
10) Besides thermogenesis, physiological uncoupling can help to ?
a) Increase ATP yield per substrate
b) Reduce reactive oxygen species production
c) Promote DNA synthesis
d) Inhibit glycolysis
Explanation:
Uncoupling proteins decrease mitochondrial membrane potential and thereby reduce reactive oxygen species production, protecting cells from oxidative damage. Apart from thermogenesis, mild uncoupling regulates metabolic efficiency and redox balance. Thus, physiological uncoupling can be cytoprotective. Correct answer is b) Reduction of reactive oxygen species by mild uncoupling in mitochondria generally.
Topic: Mitochondrial Physiology
Subtopic: Physiological Uncouplers of Oxidative Phosphorylation
Keyword Definitions:
• Uncoupler: Compound that dissipates the proton gradient across the inner mitochondrial membrane, generating heat instead of ATP.
• Thyroxine: Thyroid hormone that increases basal metabolic rate partly by mild mitochondrial uncoupling.
• Free fatty acids: Substrates that act as natural uncouplers enhancing proton leakage.
• Thermogenin: Uncoupling protein (UCP1) in brown fat responsible for non-shivering thermogenesis.
• Oxidative phosphorylation: Process coupling electron transport chain to ATP production via ATP synthase.
Lead Question - 2013
Physiological uncoupler is ?
a) Thyroxine
b) Free fatty acids
c) Thermogenin
d) All of the above
Answer & Explanation:
Physiological uncouplers include thyroid hormone, free fatty acids, and thermogenin. They naturally increase metabolic rate and thermogenesis by dissipating proton gradient in mitochondria. Thermogenin in brown fat is the most prominent, but thyroxine and fatty acids also contribute. Correct answer is d) All of the above as physiological uncouplers.
1) Clinical effect of thermogenin activity?
a) Heat generation
b) ATP accumulation
c) Hypothermia
d) Hypometabolism
Explanation:
Thermogenin (UCP1) in brown adipose tissue uncouples oxidative phosphorylation, generating heat instead of ATP. This non-shivering thermogenesis is important in neonates and cold adaptation. It prevents hypothermia by converting stored energy into body heat. Correct answer is a) Heat generation through proton gradient dissipation and enhanced oxygen consumption in mitochondria.
2) Thyroxine causes mild uncoupling by?
a) Inhibiting cytochrome oxidase
b) Enhancing proton leak across inner mitochondrial membrane
c) Inhibiting glycolysis
d) Blocking ATP synthase directly
Explanation:
Thyroxine increases basal metabolic rate by stimulating mitochondrial biogenesis and enhancing proton leakage across the inner mitochondrial membrane. This mild uncoupling raises oxygen consumption and heat production. It does not directly inhibit ATP synthase or glycolysis. Correct answer is b) Enhancing proton leak across the inner mitochondrial membrane physiologically.
3) Free fatty acids act as uncouplers by?
a) Increasing proton conductance
b) Blocking complex III
c) Inhibiting adenylate kinase
d) Reducing NADH supply
Explanation:
Free fatty acids insert into the mitochondrial inner membrane and increase proton conductance, leading to dissipation of proton motive force. This reduces ATP synthesis and increases heat generation. Thus, they act as physiological uncouplers at high concentrations. Correct answer is a) Increasing proton conductance across inner mitochondrial membrane gradients.
4) A neonate kept in cold room resists hypothermia due to?
a) White adipose tissue
b) Brown adipose tissue with thermogenin
c) Skeletal muscle glycogen
d) Liver gluconeogenesis
Explanation:
Neonates resist hypothermia through non-shivering thermogenesis mediated by thermogenin (UCP1) in brown adipose tissue. This specialized fat generates heat by uncoupling oxidative phosphorylation, protecting against cold stress. White adipose tissue mainly stores energy, not heat. Correct answer is b) Brown adipose tissue with thermogenin-mediated heat production in neonates.
5) Excess thyroxine in hyperthyroidism leads to?
a) Hypothermia
b) Increased metabolic rate and heat intolerance
c) Decreased oxygen consumption
d) Decreased heart rate
Explanation:
Hyperthyroidism increases basal metabolic rate due to mitochondrial uncoupling effects of thyroxine. Patients develop heat intolerance, weight loss despite increased appetite, tachycardia, and sweating. Correct answer is b) Increased metabolic rate and heat intolerance due to physiological uncoupling induced by elevated thyroxine hormone levels chronically.
6) In brown adipose tissue, thermogenin is located in?
a) Outer mitochondrial membrane
b) Inner mitochondrial membrane
c) Cytosol
d) Nucleus
Explanation:
Thermogenin (UCP1) is specifically located in the inner mitochondrial membrane of brown adipocytes. It acts as a proton channel, bypassing ATP synthase, dissipating proton gradient, and generating heat. Correct answer is b) Inner mitochondrial membrane where thermogenin uncoupling occurs during adaptive thermogenesis in mammals, especially infants and hibernating animals.
7) Which of the following is NOT a physiological uncoupler?
a) Thyroxine
b) Thermogenin
c) Free fatty acids
d) Cyanide
Explanation:
Cyanide is not a physiological uncoupler but a poison that inhibits cytochrome oxidase (Complex IV), halting electron transport and ATP production. Physiological uncouplers include thermogenin, thyroxine, and free fatty acids. Correct answer is d) Cyanide, which causes histotoxic hypoxia and cellular asphyxia, not uncoupling activity.
8) A patient overdosed with DNP develops hyperthermia. The mechanism is similar to?
a) Thermogenin in brown fat
b) Cyanide toxicity
c) Oligomycin inhibition
d) Rotenone inhibition
Explanation:
DNP is a chemical uncoupler that collapses the proton gradient similar to thermogenin action. It increases oxygen consumption and heat production without ATP synthesis. Cyanide and rotenone inhibit ETC complexes, while oligomycin blocks ATP synthase. Correct answer is a) Thermogenin in brown fat physiology.
9) Clinical importance of physiological uncouplers?
a) Heat production and metabolic regulation
b) ATP overproduction
c) Reduced oxygen requirement
d) Protein synthesis regulation
Explanation:
Physiological uncouplers regulate energy balance by generating heat instead of ATP, critical in neonates, hibernating animals, and adaptation to cold. They also modulate oxygen consumption and free radical generation. Correct answer is a) Heat production and metabolic regulation as their main physiological importance in humans and animals.
10) Which hormone acts as a mild physiological uncoupler by stimulating metabolism?
a) Cortisol
b) Insulin
c) Thyroxine
d) Aldosterone
Explanation:
Thyroxine increases metabolic rate partly via mitochondrial uncoupling, enhancing oxygen consumption and heat generation. This hormone elevates basal metabolic rate and energy expenditure. Insulin, cortisol, and aldosterone act by other mechanisms. Correct answer is c) Thyroxine, a mild physiological uncoupler important in metabolic and thermal regulation mechanisms naturally.
Topic: Cellular Respiration
Subtopic: Shuttles for Reducing Equivalents in Glycolysis
Keyword Definitions:
• Reducing equivalents: Electrons carried mainly by NADH or FADH₂ for ATP production.
• Malate shuttle: Pathway transferring cytosolic NADH electrons into mitochondria via malate-oxaloacetate.
• Glutamate shuttle: Transfers reducing equivalents using glutamate-aspartate transaminases.
• Carnitine: Molecule required for fatty acid transport into mitochondria, not NADH transport.
• Creatine: Energy buffer compound, not used in NADH shuttling.
Lead Question - 2013
Reducing equivalants produced in glycolysis are transported from cytosol to mitochondria by ?
a) Carnitine
b) Creatine
c) Malate shuttle
d) Glutamate shuttle
Answer & Explanation:
Cytosolic NADH cannot directly enter mitochondria. Instead, electrons are transferred by specific shuttles. The malate-aspartate shuttle is the main mechanism in most tissues, while glycerol-3-phosphate shuttle is used in some. Carnitine and creatine are unrelated. Correct answer is c) Malate shuttle for NADH transport across mitochondrial membranes.
1) In skeletal muscle, the major shuttle for NADH transfer is?
a) Malate-aspartate shuttle
b) Glycerol-3-phosphate shuttle
c) Carnitine shuttle
d) Citrate shuttle
Explanation:
Skeletal muscle primarily uses the glycerol-3-phosphate shuttle, which transfers electrons from NADH to FADH₂ at the mitochondrial membrane. This results in slightly less ATP yield compared to the malate shuttle. Correct answer is b) Glycerol-3-phosphate shuttle as the major system in skeletal muscle glycolysis.
2) Malate-aspartate shuttle transfers reducing equivalents into mitochondria as?
a) NADH
b) Malate
c) Succinate
d) Lactate
Explanation:
The malate-aspartate shuttle converts oxaloacetate into malate, which carries reducing equivalents across the mitochondrial inner membrane. Once inside, malate is reconverted to oxaloacetate, regenerating NADH in the mitochondrial matrix. Correct answer is b) Malate as the transported intermediate.
3) Which shuttle is more energy efficient?
a) Malate-aspartate shuttle
b) Glycerol-3-phosphate shuttle
c) Carnitine shuttle
d) Citrate shuttle
Explanation:
The malate-aspartate shuttle is more energy efficient because it regenerates NADH inside mitochondria, yielding ~3 ATP per NADH. The glycerol-3-phosphate shuttle regenerates FADH₂, yielding ~2 ATP per electron pair. Correct answer is a) Malate-aspartate shuttle, which maximizes ATP production.
4) A neonate with defective malate-aspartate shuttle will show?
a) Reduced ATP generation from glycolysis
b) Increased creatine levels
c) Impaired fatty acid transport
d) Enhanced gluconeogenesis
Explanation:
Defective malate-aspartate shuttle prevents cytosolic NADH reoxidation, leading to impaired ATP yield from glycolysis and possible lactic acidosis. Fatty acid transport involves carnitine, not this shuttle. Correct answer is a) Reduced ATP generation from glycolysis due to blocked NADH utilization.
5) Glutamate-aspartate shuttle is active in?
a) Liver and heart
b) Skeletal muscle only
c) Adipose tissue only
d) RBCs
Explanation:
The glutamate-aspartate shuttle is most active in liver, kidney, and heart where efficient NADH transfer is crucial for aerobic metabolism. RBCs lack mitochondria, so shuttles are absent. Correct answer is a) Liver and heart.
6) Carnitine shuttle mainly transports?
a) Fatty acids into mitochondria
b) NADH into mitochondria
c) ATP out of mitochondria
d) CO₂ into mitochondria
Explanation:
The carnitine shuttle transfers long-chain fatty acids into mitochondria for β-oxidation. It does not transport reducing equivalents. Correct answer is a) Fatty acids into mitochondria.
7) Clinical defect in carnitine shuttle presents with?
a) Hypoketotic hypoglycemia
b) Lactic acidosis
c) Hyperammonemia
d) Ketoacidosis
Explanation:
Deficiency of carnitine or CPT enzymes impairs fatty acid entry into mitochondria, preventing β-oxidation and ketone body formation. This leads to hypoketotic hypoglycemia during fasting. Correct answer is a) Hypoketotic hypoglycemia.
8) In neurons, which shuttle is predominant for NADH transfer?
a) Malate-aspartate shuttle
b) Glycerol-3-phosphate shuttle
c) Carnitine shuttle
d) Pyruvate shuttle
Explanation:
Neurons depend on the malate-aspartate shuttle to maximize ATP generation. This shuttle ensures high-energy yield for neuronal function. Correct answer is a) Malate-aspartate shuttle.
9) During hypoxia, which effect occurs due to failure of shuttles?
a) Accumulation of NADH in cytosol
b) Increased ATP from oxidative phosphorylation
c) Increased fatty acid β-oxidation
d) Enhanced electron transport chain function
Explanation:
In hypoxia, NADH reoxidation is impaired, leading to cytosolic NADH accumulation and lactate production. Correct answer is a) Accumulation of NADH in cytosol with lactic acidosis.
10) Which shuttle links glycolysis to oxidative phosphorylation most efficiently?
a) Malate-aspartate shuttle
b) Glycerol-3-phosphate shuttle
c) Carnitine shuttle
d) Citrate shuttle
Explanation:
The malate-aspartate shuttle directly couples cytosolic NADH with mitochondrial NADH, efficiently linking glycolysis to oxidative phosphorylation. Correct answer is a) Malate-aspartate shuttle.
Chapter: Carbohydrates
Topic: Monosaccharides
Subtopic: Aldoses and Ketoses
Keyword Definitions:
• Aldose: Monosaccharide with an aldehyde group.
• Ketose: Monosaccharide with a ketone group.
• Fructose: Ketohexose commonly called fruit sugar.
• Glucose: An aldohexose and primary blood sugar.
• Erythrulose: A ketotetrose, not an aldose.
Lead Question - 2013
Which of the following is Aldosugar ?
a) Fructose
b) Erythrulose
c) Glucose
d) None
Answer & Explanation:
Aldoses are sugars containing an aldehyde group at carbon one. Among the options, glucose is an aldohexose, while fructose and erythrulose are ketoses. Therefore, the correct answer is c) Glucose. Aldoses play a major role in glycolysis, gluconeogenesis, and as precursors for polysaccharides.
1) Which of the following is a ketohexose?
a) Glucose
b) Fructose
c) Galactose
d) Mannose
Explanation:
Ketohexoses contain six carbons and a ketone group. Fructose is the most common ketohexose, found in fruits and honey. Glucose, galactose, and mannose are aldohexoses. Correct answer is b) Fructose, an important dietary sugar metabolized in the liver via fructolysis.
2) Which sugar is an aldotetrose?
a) Erythrose
b) Ribose
c) Erythrulose
d) Fructose
Explanation:
Aldotetroses are four-carbon sugars with an aldehyde group. Erythrose is an aldotetrose, important in the pentose phosphate pathway. Ribose is a pentose, while erythrulose is a ketotetrose. Correct answer is a) Erythrose.
3) A patient with essential fructosuria cannot metabolize which sugar?
a) Glucose
b) Fructose
c) Galactose
d) Mannose
Explanation:
Essential fructosuria results from deficiency of fructokinase. This prevents phosphorylation of fructose, leading to benign fructose accumulation in urine. Glucose, galactose, and mannose metabolism remain normal. Correct answer is b) Fructose.
4) Which aldose sugar is a component of RNA?
a) Deoxyribose
b) Ribose
c) Glucose
d) Arabinose
Explanation:
RNA contains ribose, an aldopentose, with an OH group at carbon 2. DNA contains deoxyribose lacking this OH. Correct answer is b) Ribose, which stabilizes RNA and participates in nucleotide structure.
5) A neonate with vomiting and hypoglycemia after milk feeding likely has?
a) Galactosemia
b) Fructosuria
c) Essential pentosuria
d) Glycogen storage disease
Explanation:
Galactosemia occurs due to galactose-1-phosphate uridyltransferase deficiency, leading to hypoglycemia, vomiting, and jaundice after milk intake. Correct answer is a) Galactosemia.
6) Which sugar is both an aldohexose and the most abundant monosaccharide in blood?
a) Galactose
b) Fructose
c) Glucose
d) Mannose
Explanation:
Glucose, an aldohexose, is the main blood sugar and universal energy substrate. Its regulation is critical for homeostasis. Correct answer is c) Glucose.
7) Which monosaccharide accumulates in hereditary fructose intolerance?
a) Glucose
b) Fructose-1-phosphate
c) Galactose
d) Mannose
Explanation:
Hereditary fructose intolerance is due to aldolase B deficiency, causing accumulation of fructose-1-phosphate. This traps phosphate, impairs gluconeogenesis, and causes hypoglycemia. Correct answer is b) Fructose-1-phosphate.
8) Which aldose sugar is most important in glycolysis entry?
a) Galactose
b) Glucose
c) Fructose
d) Mannose
Explanation:
Glucose is the primary aldose metabolized in glycolysis, providing ATP for cellular functions. Correct answer is b) Glucose.
9) In a diabetic patient with uncontrolled hyperglycemia, which pathway converts excess glucose to sorbitol?
a) Polyol pathway
b) Glycolysis
c) Pentose phosphate pathway
d) Gluconeogenesis
Explanation:
In hyperglycemia, excess glucose is reduced to sorbitol by aldose reductase via the polyol pathway. Sorbitol accumulation causes cataracts and neuropathy. Correct answer is a) Polyol pathway.
10) Which sugar is a ketotetrose?
a) Erythrulose
b) Erythrose
c) Ribose
d) Arabinose
Explanation:
Ketotetroses are four-carbon sugars with a ketone group. Erythrulose is the classic ketotetrose. Erythrose is an aldotetrose, ribose a pentose, and arabinose an aldopentose. Correct answer is a) Erythrulose.
Chapter: Carbohydrate Metabolism
Topic: Glycolysis
Subtopic: Regulation of Phosphofructokinase-1 (PFK-1)
Keyword Definitions:
• PFK-1: Key regulatory enzyme of glycolysis converting fructose-6-phosphate to fructose-1,6-bisphosphate.
• AMP: Activator of glycolysis during low energy states.
• Citrate: TCA cycle intermediate and negative regulator of PFK-1.
• Glucose-6-phosphate: Regulates hexokinase, not PFK-1 directly.
• Insulin: Hormone promoting glycolysis.
Lead Question - 2013
PFK-I inhibitor ?
a) AMP
b) Citrate
c) Glucose 6 phosphate
d) Insulin
Answer & Explanation:
Phosphofructokinase-1 (PFK-1) is the rate-limiting enzyme of glycolysis. It is activated by AMP and fructose-2,6-bisphosphate. Citrate, a TCA cycle intermediate, inhibits PFK-1, linking glycolysis with the Krebs cycle. Correct answer is b) Citrate. This ensures glycolysis slows when cellular energy is already sufficient.
1) Which is the rate-limiting enzyme of glycolysis?
a) Hexokinase
b) PFK-1
c) Pyruvate kinase
d) Glucose-6-phosphate dehydrogenase
Explanation:
The rate-limiting enzyme of glycolysis is phosphofructokinase-1 (PFK-1). It catalyzes the irreversible conversion of fructose-6-phosphate to fructose-1,6-bisphosphate. This step commits glucose to glycolysis. Regulation is by allosteric activators (AMP, F-2,6-BP) and inhibitors (ATP, citrate). Correct answer is b) PFK-1.
2) Which metabolite is an allosteric activator of PFK-1?
a) ATP
b) Citrate
c) Fructose-2,6-bisphosphate
d) Acetyl-CoA
Explanation:
Fructose-2,6-bisphosphate is the most potent activator of PFK-1. It overrides inhibition by ATP and promotes glycolysis even in energy-rich states. Correct answer is c) Fructose-2,6-bisphosphate. This mechanism ensures balance between glycolysis and gluconeogenesis in the liver.
3) A patient with liver PFK-1 deficiency will have?
a) Impaired glycolysis
b) Excess lactate production
c) Increased glycogenolysis
d) Increased gluconeogenesis
Explanation:
PFK-1 deficiency impairs glycolysis, leading to exercise intolerance, hypoglycemia, and muscle weakness. Lactate production decreases as glucose metabolism stalls. Correct answer is a) Impaired glycolysis.
4) Which enzyme links glycolysis with the pentose phosphate pathway?
a) PFK-1
b) Glucose-6-phosphate dehydrogenase
c) Pyruvate kinase
d) Hexokinase
Explanation:
Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway. It diverts glucose-6-phosphate away from glycolysis to generate NADPH and ribose-5-phosphate. Correct answer is b) Glucose-6-phosphate dehydrogenase.
5) Which enzyme deficiency causes exercise-induced muscle cramps and myoglobinuria?
a) Hexokinase
b) PFK-1 (Tarui disease)
c) Glucose-6-phosphatase
d) Pyruvate dehydrogenase
Explanation:
PFK-1 deficiency in muscles is known as Tarui disease, a glycogen storage disorder (Type VII). It presents with cramps, weakness, and myoglobinuria after exercise. Correct answer is b) PFK-1.
6) Which metabolite inhibits both PFK-1 and pyruvate kinase?
a) Citrate
b) ATP
c) Acetyl-CoA
d) NADH
Explanation:
High ATP levels inhibit PFK-1 and pyruvate kinase, reducing glycolysis when energy is abundant. Correct answer is b) ATP. This feedback regulation maintains energy homeostasis.
7) A patient with sepsis develops increased glycolysis. Which metabolite activates PFK-1 under hypoxia?
a) ATP
b) Fructose-2,6-bisphosphate
c) Citrate
d) NADPH
Explanation:
During hypoxia, anaerobic glycolysis increases. Fructose-2,6-bisphosphate strongly activates PFK-1, ensuring rapid ATP production. Correct answer is b) Fructose-2,6-bisphosphate.
8) Which enzyme catalyzes the final step of glycolysis?
a) PFK-1
b) Pyruvate kinase
c) Lactate dehydrogenase
d) Aldolase
Explanation:
Pyruvate kinase catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate, generating ATP. Correct answer is b) Pyruvate kinase.
9) A patient with ischemic heart disease has increased anaerobic glycolysis. Which end product accumulates?
a) Pyruvate
b) Lactate
c) Acetyl-CoA
d) Citrate
Explanation:
Under anaerobic conditions, pyruvate is converted to lactate by lactate dehydrogenase. This regenerates NAD+, sustaining glycolysis. Lactate accumulates in ischemic tissue. Correct answer is b) Lactate.
10) Which enzyme deficiency leads to hemolytic anemia due to impaired glycolysis in RBCs?
a) Hexokinase
b) Pyruvate kinase
c) PFK-1
d) Aldolase
Explanation:
Pyruvate kinase deficiency is a common cause of nonspherocytic hemolytic anemia. RBCs depend solely on glycolysis for ATP, and deficiency impairs ion pumps, causing hemolysis. Correct answer is b) Pyruvate kinase.
Chapter: Carbohydrate Metabolism
Topic: Glycolysis
Subtopic: Regulation of Phosphofructokinase-1 (PFK-1)
Keyword Definitions:
• Phosphofructokinase-1 (PFK-1): Key regulatory enzyme of glycolysis converting fructose-6-phosphate to fructose-1,6-bisphosphate.
• Allosteric activator: Molecule binding at a site other than the active site, increasing enzyme activity.
• Fructose-2,6-bisphosphate: Potent activator of PFK-1, promoting glycolysis.
• PEP (Phosphoenolpyruvate): Glycolytic intermediate, usually an inhibitor of PFK-1.
• Feedback control: Mechanism by which downstream products regulate upstream enzymes.
Lead Question - 2013
Phosphofructokinase-1 occupies a key position in regulating glycolysis and is also subjected to feedback control. Which among the following is the allosteric activators of phosphofructokinase-1?
a) Fructose 2, 3 bisphosphate
b) Fructose 2, 6 bisphosphate
c) Glucokinase
d) PEP
Answer & Explanation:
Fructose-2,6-bisphosphate is the most potent allosteric activator of PFK-1. It enhances glycolysis by overriding ATP-mediated inhibition, especially in the liver. Other regulators like AMP also activate PFK-1, but F-2,6-BP is dominant. Correct answer is b) Fructose-2,6-bisphosphate.
1) Which enzyme catalyzes the committed step of glycolysis?
a) Hexokinase
b) PFK-1
c) Pyruvate kinase
d) Aldolase
Explanation:
The committed step of glycolysis is catalyzed by PFK-1, converting fructose-6-phosphate to fructose-1,6-bisphosphate. It is the most regulated step, controlled by ATP, AMP, citrate, and fructose-2,6-bisphosphate. Correct answer is b) PFK-1.
2) Which molecule is the strongest activator of PFK-1 in hepatocytes?
a) AMP
b) ATP
c) Fructose-2,6-bisphosphate
d) NADH
Explanation:
Fructose-2,6-bisphosphate is the strongest activator of PFK-1 in hepatocytes. It ensures glycolysis proceeds even when ATP levels are high. Correct answer is c) Fructose-2,6-bisphosphate.
3) A patient with liver disease shows defective fructose-2,6-bisphosphate synthesis. Which pathway is most impaired?
a) Glycogenolysis
b) Gluconeogenesis inhibition
c) Glycolysis
d) TCA cycle
Explanation:
Absence of fructose-2,6-bisphosphate reduces PFK-1 activity, impairing glycolysis and promoting gluconeogenesis. Correct answer is c) Glycolysis.
4) Which enzyme deficiency causes Tarui disease (Glycogen storage disorder type VII)?
a) Hexokinase
b) PFK-1
c) Glucose-6-phosphatase
d) Pyruvate kinase
Explanation:
Tarui disease is caused by deficiency of PFK-1 in muscles, leading to exercise intolerance, cramps, and myoglobinuria. Correct answer is b) PFK-1.
5) Which metabolite inhibits PFK-1 activity?
a) AMP
b) Citrate
c) Fructose-2,6-bisphosphate
d) ADP
Explanation:
Citrate, a TCA cycle intermediate, inhibits PFK-1 activity. High citrate levels indicate sufficient energy, slowing glycolysis. Correct answer is b) Citrate.
6) During hypoxia, PFK-1 is primarily activated by?
a) ATP
b) AMP
c) Citrate
d) Acetyl-CoA
Explanation:
During hypoxia, ATP decreases and AMP accumulates. AMP directly activates PFK-1, stimulating glycolysis to produce ATP anaerobically. Correct answer is b) AMP.
7) Which is a feedback inhibitor of PFK-1?
a) NADPH
b) ATP
c) ADP
d) AMP
Explanation:
High ATP levels feedback inhibit PFK-1, signaling sufficient cellular energy. This reduces glycolysis. Correct answer is b) ATP.
8) In septic patients, glycolysis is enhanced due to increased levels of?
a) Citrate
b) Fructose-2,6-bisphosphate
c) NADPH
d) Acetyl-CoA
Explanation:
In sepsis, glycolysis is enhanced by increased fructose-2,6-bisphosphate, ensuring ATP production under stress. Correct answer is b) Fructose-2,6-bisphosphate.
9) Which enzyme catalyzes conversion of fructose-1,6-bisphosphate to DHAP and G3P?
a) Aldolase
b) PFK-1
c) Pyruvate kinase
d) Enolase
Explanation:
Aldolase splits fructose-1,6-bisphosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). Correct answer is a) Aldolase.
10) In RBCs, increased 2,3-bisphosphoglycerate levels will?
a) Activate PFK-1 strongly
b) Decrease oxygen affinity of hemoglobin
c) Inhibit glycolysis
d) Increase ATP generation directly
Explanation:
2,3-bisphosphoglycerate decreases hemoglobin’s oxygen affinity, facilitating oxygen release to tissues. It does not directly regulate PFK-1. Correct answer is b) Decrease oxygen affinity of hemoglobin.
Topic: Enzyme Regulation in Glycolysis
Subtopic: Hexokinase Regulation
Keyword Definitions:
• Hexokinase: Enzyme catalyzing phosphorylation of glucose to glucose-6-phosphate in glycolysis.
• Glucose-6-phosphate: Product of the hexokinase reaction, acts as a feedback inhibitor.
• Feedback inhibition: Process where an end product inhibits the enzyme that catalyzed its formation.
• Insulin: Hormone promoting glucose uptake and utilization.
• Glucagon: Hormone increasing blood glucose by promoting glycogen breakdown.
Lead Question - 2013
Hexokinase is inhibited by ?
a) Glucose-6-phosphate
b) Glucagon
c) Glucose
d) Insulin
Explanation: Hexokinase, the key glycolytic enzyme, is regulated by product inhibition. It is inhibited by Glucose-6-phosphate, ensuring balanced glucose utilization. This feedback mechanism prevents excessive phosphorylation of glucose when energy supply is sufficient, maintaining cellular homeostasis and conserving ATP for critical needs.
1) A patient with high blood glucose but normal insulin levels likely has impaired regulation of hexokinase by:
a) Glucagon
b) Glucose-6-phosphate
c) ATP
d) NADH
Explanation: Impaired feedback inhibition of hexokinase by Glucose-6-phosphate can cause continuous glucose phosphorylation despite adequate insulin. This clinical condition may contribute to metabolic imbalance and energy wastage, highlighting the importance of product inhibition in glycolysis regulation.
2) Which enzyme catalyzes the first irreversible step of glycolysis?
a) Hexokinase
b) Phosphofructokinase-1
c) Pyruvate kinase
d) Aldolase
Explanation: Hexokinase catalyzes the first irreversible step of glycolysis, phosphorylating glucose to glucose-6-phosphate. This commits glucose to metabolic pathways inside the cell, preventing its escape and marking the beginning of glycolysis.
3) In red blood cells, hexokinase inhibition leads to decreased:
a) Oxygen binding
b) ATP production
c) 2,3-BPG synthesis
d) CO₂ transport
Explanation: In red blood cells, glycolysis is the sole ATP source. Inhibition of hexokinase decreases glycolytic flux, reducing ATP production. This impairs energy-dependent processes such as ion pumping and membrane stability, leading to hemolysis.
4) Which of the following acts as an isoenzyme of hexokinase with low affinity but high capacity for glucose?
a) Hexokinase I
b) Hexokinase II
c) Glucokinase
d) Aldolase
Explanation: Glucokinase, an isoenzyme of hexokinase in liver and pancreas, has low affinity but high capacity for glucose. Unlike hexokinase, it is not inhibited by glucose-6-phosphate, allowing liver cells to trap glucose effectively after meals.
5) Which of the following best describes the Km of hexokinase compared to glucokinase?
a) High Km
b) Low Km
c) Same Km
d) Zero Km
Explanation: Hexokinase has a low Km for glucose, meaning high affinity. This allows it to function efficiently even at low glucose concentrations, unlike glucokinase which has high Km and is active only when glucose levels are elevated.
6) A neonate presenting with hypoglycemia may have a mutation in which enzyme?
a) Hexokinase
b) Glucokinase
c) Phosphofructokinase-1
d) Pyruvate kinase
Explanation: Mutations in Glucokinase impair the ability of pancreatic beta cells to sense glucose properly, leading to inappropriate insulin secretion and hypoglycemia. Clinical identification of such mutations is important for managing neonatal metabolic disorders.
7) Which cofactor is required for hexokinase activity?
a) Mg²⁺
b) Ca²⁺
c) Zn²⁺
d) Fe²⁺
Explanation: Mg²⁺ acts as a cofactor for hexokinase by stabilizing ATP during the phosphorylation of glucose. This ensures efficient transfer of the phosphate group in the glycolytic pathway.
8) Which organ has glucokinase activity but not hexokinase activity as dominant?
a) Brain
b) Muscle
c) Liver
d) Red blood cells
Explanation: The liver predominantly uses glucokinase, which is specialized to handle high glucose concentrations after meals. This ensures efficient glucose uptake and storage as glycogen, supporting whole-body glucose regulation.
9) Which of the following is a competitive inhibitor of hexokinase?
a) Glucose analog 2-deoxyglucose
b) Fructose
c) Lactose
d) Galactose
Explanation: 2-deoxyglucose is a competitive inhibitor of hexokinase. It is phosphorylated but cannot proceed further in glycolysis, thus blocking glucose utilization and ATP production, used experimentally and in cancer therapy research.
10) In glycolysis, the inhibition of hexokinase prevents accumulation of which metabolite?
a) Pyruvate
b) Glucose-6-phosphate
c) Fructose-6-phosphate
d) ATP
Explanation: Inhibition of hexokinase prevents formation of Glucose-6-phosphate, the immediate product of glucose phosphorylation. This controls glycolytic entry and avoids unnecessary trapping of glucose in cells.
Topic: Metabolic Regulation in Fasting
Subtopic: Enzyme Activity during Starvation
Keyword Definitions:
• Fasting/Starvation: A metabolic state where the body shifts from glucose utilization to fat and ketone metabolism.
• Hexokinase: Enzyme catalyzing phosphorylation of glucose in glycolysis.
• Glucokinase: Liver enzyme with high Km for glucose, active postprandially.
• PDH (Pyruvate Dehydrogenase): Converts pyruvate to acetyl-CoA for TCA cycle.
• Pyruvate Kinase: Enzyme catalyzing conversion of phosphoenolpyruvate to pyruvate in glycolysis.
Lead Question - 2013
All of the following are inhibited during fasting/ starvation, except ?
a) Hexokinase
b) Glucokinase
c) PDH
d) Pyruvate kinase
Explanation: During fasting, glycolytic and oxidative enzymes such as Glucokinase, Pyruvate kinase, and PDH are inhibited to conserve glucose. Hexokinase, however, continues functioning in essential tissues like the brain and red blood cells. Hence, Hexokinase is not inhibited, ensuring glucose utilization in critical organs.
1) In fasting state, which hormone primarily regulates suppression of glycolytic enzymes?
a) Insulin
b) Glucagon
c) Cortisol
d) Epinephrine
Explanation: Glucagon dominates during fasting, reducing glycolytic enzyme activity and promoting gluconeogenesis. By lowering insulin and activating cAMP pathways, glucagon shifts metabolism from glucose utilization to fat oxidation, preserving glucose for essential tissues like the brain and red blood cells.
2) PDH deficiency in a child presents with which major clinical feature?
a) Hypoglycemia
b) Lactic acidosis
c) Ketoacidosis
d) Hyperammonemia
Explanation: Lactic acidosis occurs in PDH deficiency due to accumulation of pyruvate, which is shunted to lactate. Patients present with neurological dysfunction, muscle weakness, and metabolic acidosis. Early diagnosis and ketogenic diet therapy can improve prognosis in such metabolic disorders.
3) Which tissue continues to use glucose during prolonged fasting?
a) Skeletal muscle
b) Brain
c) Liver
d) Adipose tissue
Explanation: The brain continues to use glucose during fasting, although it gradually adapts to ketone body utilization. RBCs also rely exclusively on glucose since they lack mitochondria, emphasizing the need for basal glucose metabolism even in starvation.
4) A patient with fasting hypoglycemia is most likely deficient in which enzyme?
a) Glucokinase
b) Pyruvate kinase
c) Hexokinase
d) Glycogen phosphorylase
Explanation: Glucokinase deficiency in the liver impairs glucose phosphorylation and storage as glycogen after meals. This leads to fasting hypoglycemia, since glycogen stores are limited and glucose metabolism is poorly regulated.
5) During starvation, activity of pyruvate kinase is inhibited by which mechanism?
a) Allosteric activation by F1,6BP
b) Inhibition by ATP
c) Phosphorylation by glucagon-mediated kinases
d) Activation by citrate
Explanation: Pyruvate kinase is inhibited in fasting through phosphorylation mediated by glucagon. This prevents glycolysis and diverts substrates for gluconeogenesis. ATP and alanine also contribute to inhibition, conserving energy and ensuring glucose availability for vital tissues.
6) In prolonged fasting, which pathway becomes the major source of glucose?
a) Glycolysis
b) Glycogenolysis
c) Gluconeogenesis
d) Pentose phosphate pathway
Explanation: Gluconeogenesis is the major pathway for glucose supply during prolonged fasting. It uses substrates like lactate, glycerol, and amino acids, sustaining blood glucose for essential tissues when glycogen stores are depleted.
7) Which enzyme is upregulated in starvation to support gluconeogenesis?
a) Hexokinase
b) Glucokinase
c) PEP carboxykinase
d) Pyruvate kinase
Explanation: PEP carboxykinase is upregulated during fasting, converting oxaloacetate to phosphoenolpyruvate, a crucial step in gluconeogenesis. This enzyme ensures continued glucose production for brain and RBCs, compensating for reduced glycolysis.
8) A patient in prolonged starvation develops muscle wasting due to excessive use of which substrate for gluconeogenesis?
a) Fatty acids
b) Amino acids
c) Lactate
d) Ketone bodies
Explanation: Amino acids from muscle proteins are used extensively for gluconeogenesis in prolonged starvation. This results in muscle wasting and nitrogen loss, although ketone body adaptation later reduces protein breakdown.
9) Which glycolytic enzyme is bypassed in gluconeogenesis by glucose-6-phosphatase?
a) Hexokinase
b) Phosphofructokinase-1
c) Pyruvate kinase
d) Enolase
Explanation: Hexokinase catalyzes phosphorylation of glucose to glucose-6-phosphate. In gluconeogenesis, this is bypassed by glucose-6-phosphatase, which dephosphorylates glucose-6-phosphate to free glucose, enabling its release into the blood by liver cells.
10) During starvation, acetyl-CoA produced from β-oxidation primarily enters which pathway?
a) TCA cycle
b) Gluconeogenesis
c) Ketogenesis
d) Urea cycle
Explanation: In starvation, acetyl-CoA from fatty acid β-oxidation primarily enters ketogenesis in the liver. This produces ketone bodies (acetoacetate, β-hydroxybutyrate), which serve as alternate fuels for brain and muscle, sparing glucose and protein stores.
Topic: Gluconeogenesis
Subtopic: Substrates of Gluconeogenesis
Keyword Definitions:
• Gluconeogenesis: Process of synthesizing glucose from non-carbohydrate precursors, mainly in liver and kidney.
• Oleate: A long-chain fatty acid, provides energy but cannot yield net glucose.
• Succinate: TCA cycle intermediate that contributes carbon skeletons for gluconeogenesis.
• Glutamate: Amino acid converted to α-ketoglutarate, entering gluconeogenesis.
• Aspartate: Amino acid feeding oxaloacetate, a gluconeogenic substrate.
Lead Question - 2013
All are used in gluconeogenesis except ?
a) Oleate
b) Succinate
c) Glutamate
d) Aspartate
Explanation: Gluconeogenesis requires carbon skeletons from amino acids and TCA intermediates. Succinate, Glutamate, and Aspartate contribute carbons for glucose synthesis. Oleate, a pure fatty acid, undergoes β-oxidation to yield acetyl-CoA, which cannot be converted to glucose due to irreversible pyruvate dehydrogenase step. Thus, oleate is not used.
1) Which amino acid directly enters gluconeogenesis via conversion to oxaloacetate?
a) Alanine
b) Aspartate
c) Glutamate
d) Serine
Explanation: Aspartate directly transaminates to oxaloacetate, a crucial substrate for gluconeogenesis. This allows efficient glucose production in fasting state, especially in liver. Thus, aspartate is classified as a glucogenic amino acid.
2) A child with fatty acid oxidation disorder develops hypoglycemia. Why?
a) Ketone overproduction
b) Lack of NADH for gluconeogenesis
c) Excessive glycogen breakdown
d) Hyperactive PDH complex
Explanation: In fatty acid oxidation defects, NADH generation is impaired, reducing energy for gluconeogenesis. This leads to fasting hypoglycemia and low ketone production, a hallmark of these disorders.
3) Which of the following is a purely ketogenic amino acid?
a) Glutamate
b) Lysine
c) Aspartate
d) Alanine
Explanation: Lysine is purely ketogenic and cannot yield glucose. It is converted to acetyl-CoA, which enters ketogenesis. Glucogenic amino acids like alanine, aspartate, and glutamate provide carbon skeletons for gluconeogenesis.
4) Which pathway supplies glycerol for gluconeogenesis?
a) Lipolysis
b) Glycolysis
c) Pentose phosphate pathway
d) TCA cycle
Explanation: Lipolysis of triglycerides releases glycerol, which is converted to dihydroxyacetone phosphate (DHAP), a gluconeogenic substrate. This process is crucial during prolonged fasting, when glycerol becomes a significant glucose source.
5) A patient with PDH deficiency cannot use pyruvate for acetyl-CoA formation. Pyruvate is instead shunted to?
a) Oxaloacetate
b) Fumarate
c) Citrate
d) Malate
Explanation: In PDH deficiency, pyruvate cannot convert to acetyl-CoA. Instead, it is carboxylated to oxaloacetate via pyruvate carboxylase, fueling gluconeogenesis. This compensatory mechanism helps prevent hypoglycemia, though lactic acidosis is common.
6) Which hormone stimulates gluconeogenesis most strongly?
a) Insulin
b) Glucagon
c) Growth hormone
d) Thyroxine
Explanation: Glucagon is the primary stimulator of gluconeogenesis. It activates cAMP and increases expression of gluconeogenic enzymes such as PEP carboxykinase, ensuring glucose availability during fasting.
7) Why can odd-chain fatty acids contribute to gluconeogenesis?
a) They produce acetyl-CoA
b) They produce succinyl-CoA
c) They produce citrate
d) They produce oxaloacetate
Explanation: Odd-chain fatty acids yield succinyl-CoA, which enters the TCA cycle and serves as a gluconeogenic substrate. In contrast, even-chain fatty acids yield only acetyl-CoA, which cannot produce net glucose.
8) A patient with chronic alcoholism has impaired gluconeogenesis due to excess NADH. Which intermediate is reduced to lactate?
a) Malate
b) Pyruvate
c) Oxaloacetate
d) Acetyl-CoA
Explanation: Excess NADH in alcoholism drives conversion of pyruvate to lactate, blocking its entry into gluconeogenesis. This results in lactic acidosis and hypoglycemia.
9) Which enzyme catalyzes the final step of gluconeogenesis, releasing free glucose?
a) Pyruvate carboxylase
b) PEP carboxykinase
c) Glucose-6-phosphatase
d) Fructose-1,6-bisphosphatase
Explanation: Glucose-6-phosphatase catalyzes the last step of gluconeogenesis, converting glucose-6-phosphate to free glucose. This enzyme is present in the liver and kidney, but absent in muscle, preventing glucose release from muscle glycogen.
10) In gluconeogenesis, which enzyme bypasses phosphofructokinase-1?
a) Pyruvate carboxylase
b) Glucose-6-phosphatase
c) Fructose-1,6-bisphosphatase
d) PEP carboxykinase
Explanation: Fructose-1,6-bisphosphatase bypasses PFK-1, converting fructose-1,6-bisphosphate to fructose-6-phosphate. This is a key regulatory step, stimulated by ATP and inhibited by AMP and fructose-2,6-bisphosphate.
Topic: Carbohydrate Metabolism
Subtopic: Oxidative Decarboxylation of Pyruvate
Keyword Definitions:
• Thiamine: A coenzyme (TPP) needed for oxidative decarboxylation.
• Niacin: Vitamin B3, precursor of NAD⁺ used in redox reactions.
• Riboflavin: Vitamin B2, precursor of FAD, essential in oxidation reactions.
• Biotin: Vitamin B7, functions as a CO₂ carrier in carboxylation reactions.
• Pyruvate Dehydrogenase Complex: Multienzyme system converting pyruvate to acetyl-CoA.
Lead Question - 2013
Which of the following vitamins does not participate in oxidative decarboxylation of pyruvate to acetyl CoA?
a) Thiamine
b) Niacine
c) Riboflavin
d) Biotin
Explanation:
The oxidative decarboxylation of pyruvate requires thiamine (TPP), riboflavin (FAD), niacin (NAD⁺), and lipoic acid. Biotin, however, functions in carboxylation reactions and not in this pathway. Thus, the vitamin not involved is Biotin (Answer: d). This distinction is vital in metabolism understanding.
1) Pyruvate dehydrogenase complex requires which cofactor?
a) Biotin
b) Lipoic acid
c) Vitamin K
d) Vitamin C
Explanation:
Pyruvate dehydrogenase complex requires thiamine pyrophosphate, FAD, NAD⁺, coenzyme A, and lipoic acid as cofactors. Biotin and vitamins C, K are not part of this complex. Hence, the correct cofactor here is Lipoic acid (Answer: b). This is essential for acetyl-CoA generation from pyruvate.
2) A patient with thiamine deficiency will primarily show impaired:
a) Glycolysis
b) Pyruvate to Acetyl-CoA conversion
c) Glycogenolysis
d) Gluconeogenesis
Explanation:
Thiamine deficiency impairs pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, blocking acetyl-CoA production. Glycolysis itself continues normally. Thus, the impaired process is Pyruvate to Acetyl-CoA conversion (Answer: b). This explains neurological symptoms in thiamine deficiency such as Wernicke-Korsakoff syndrome.
3) Which vitamin deficiency mimics arsenic poisoning due to PDH inhibition?
a) Biotin
b) Niacin
c) Thiamine
d) Riboflavin
Explanation:
Both thiamine deficiency and arsenic toxicity inhibit pyruvate dehydrogenase complex, causing pyruvate accumulation and lactic acidosis. Therefore, the vitamin whose deficiency mimics arsenic poisoning is Thiamine (Answer: c). This association is clinically important in neurological manifestations and metabolic acidosis.
4) A child presents with lactic acidosis and neurological symptoms. Deficiency of which enzyme is suspected?
a) Glucokinase
b) Pyruvate carboxylase
c) Pyruvate dehydrogenase
d) Hexokinase
Explanation:
Defective pyruvate dehydrogenase prevents conversion of pyruvate to acetyl-CoA, leading to accumulation of lactate and neurological dysfunction. Thus, the deficient enzyme is Pyruvate dehydrogenase (Answer: c). This clinical presentation is consistent with PDH deficiency, a rare but serious metabolic disorder.
5) Which cofactor of PDH complex is derived from riboflavin?
a) NAD⁺
b) CoA
c) TPP
d) FAD
Explanation:
Riboflavin (Vitamin B2) is the precursor of FAD, a crucial cofactor in oxidative decarboxylation. TPP comes from thiamine, NAD⁺ from niacin, and CoA from pantothenic acid. Therefore, the riboflavin-derived cofactor is FAD (Answer: d). This role is essential in redox metabolism of carbohydrates.
6) Which vitamin deficiency will impair both PDH and α-ketoglutarate dehydrogenase complexes?
a) Thiamine
b) Biotin
c) Vitamin C
d) Vitamin K
Explanation:
Both PDH and α-ketoglutarate dehydrogenase require thiamine pyrophosphate (TPP) as a cofactor. Hence, thiamine deficiency affects both pathways, leading to reduced ATP production. Therefore, the correct answer is Thiamine (Answer: a). This explains neurological and cardiac symptoms seen in beriberi and Wernicke’s encephalopathy.
7) A patient with biotin deficiency will show impairment in which pathway?
a) Glycolysis
b) Gluconeogenesis
c) Oxidative decarboxylation
d) Glycogenolysis
Explanation:
Biotin is a coenzyme in carboxylation reactions such as pyruvate carboxylase in gluconeogenesis. Its deficiency causes impaired gluconeogenesis and hypoglycemia. Therefore, the affected pathway is Gluconeogenesis (Answer: b). This distinguishes biotin’s role from vitamins involved in oxidative decarboxylation of pyruvate.
8) Which of the following is not a cofactor of pyruvate dehydrogenase complex?
a) NAD⁺
b) FAD
c) Biotin
d) Lipoic acid
Explanation:
The pyruvate dehydrogenase complex requires TPP, FAD, NAD⁺, CoA, and lipoic acid. Biotin is not involved in this process but functions in carboxylation reactions. Hence, the correct answer is Biotin (Answer: c). This clarifies the specific cofactor requirements of PDH complex in energy metabolism.
9) Which clinical condition results from PDH complex deficiency?
a) Hypoglycemia
b) Lactic acidosis
c) Hyperammonemia
d) Gout
Explanation:
A deficiency of PDH complex leads to accumulation of pyruvate, which is shunted to lactate, causing lactic acidosis. This is a hallmark clinical feature. Hence, the condition caused is Lactic acidosis (Answer: b). This explains neurological deficits and metabolic disturbances in patients with PDH deficiency.
10) A newborn with failure to thrive and lactic acidosis most likely has deficiency of:
a) Pyruvate carboxylase
b) Pyruvate dehydrogenase
c) Fructokinase
d) Aldolase B
Explanation:
Deficiency of pyruvate dehydrogenase results in lactic acidosis and poor energy production, leading to failure to thrive. Pyruvate carboxylase deficiency causes hypoglycemia, while aldolase B affects fructose metabolism. Thus, the newborn’s condition suggests Pyruvate dehydrogenase deficiency (Answer: b). This highlights the clinical importance of PDH in metabolism.
11) Which vitamin-derived cofactor is common to PDH and transketolase?
a) Biotin
b) Riboflavin
c) Thiamine
d) Niacin
Explanation:
Both PDH complex and transketolase require thiamine pyrophosphate (TPP) derived from thiamine. This forms the basis of the thiamine deficiency test using erythrocyte transketolase activity. Therefore, the common vitamin-derived cofactor is Thiamine (Answer: c). This illustrates overlapping roles of vitamins in metabolic pathways.