With 21 questions, in this section, you’ll explore real-world applications of biochemistry, sharpen your critical thinking, and connect biochemical concepts to clinical insights. Dive in, think deeply, and discover the fascinating intricacies of metabolic pathways.
1. A 35-year-old factory worker is brought to the emergency department after accidental exposure to cyanide fumes. The patient presents with confusion, rapid breathing, and metabolic acidosis. Blood tests reveal elevated lactate levels. Inhibition of oxidative phosphorylation by cyanide ion leads to an increase in which of the following?
A. Gluconeogenesis provides more glucose for metabolism
B. Transport of ADP into the mitochondria
C. Utilization of fatty acid substrates to augment glucose utilization
D. Utilization of ketone bodies for energy generation
E. Lactic acid in the blood causing acidosis
Correct Answer: E. Lactic acid in the blood causing acidosis
Brief Explanation:
Cyanide inhibits cytochrome c oxidase (Complex IV) in the electron transport chain, halting oxidative phosphorylation and ATP production. As a result, cells switch to anaerobic glycolysis for energy, leading to increased production of lactic acid. The accumulation of lactate causes lactic acidosis, which is a hallmark of cyanide poisoning. Other metabolic pathways, such as gluconeogenesis or ketone body utilization, do not play a significant compensatory role in this context.
2. A 40-year-old patient presents with sudden weight loss despite maintaining a normal appetite. Investigations reveal a metabolic disorder characterized by excessive glucose consumption in muscle cells due to an abnormally high rate of glycolysis. Which of the following enzymes is most likely responsible for the loss of regulation in glycolysis?
A. Hexokinase
B. Glucokinase
C. PFK-1
D. PFK-2
E. Pyruvate kinase
Correct Answer: C. PFK-1
Explanation:
Phosphofructokinase-1 (PFK-1) is the rate-limiting enzyme of glycolysis and tightly regulates the pathway. Loss of control over PFK-1 can lead to excessive glycolysis, resulting in increased glucose consumption. This could explain the weight loss, as energy production becomes abnormally dependent on glycolysis despite normal glucose levels. PFK-1 activity is normally regulated by allosteric modulators like ATP, AMP, and fructose 2,6-bisphosphate. Dysregulation of this enzyme bypasses these controls, driving uncontrolled glycolysis. Other enzymes, like hexokinase or pyruvate kinase, do not have as central a role in rate regulation.
3. A researcher working with a mouse model observes that the upregulation of fatty acid oxidation leads to excess ATP production, which downregulates glycolysis. This results in the reduced production of a glycolytic intermediate. Which of the following intermediates is likely produced in significantly lower concentrations?
A. Glucose 6-phosphate
B. Fructose 6-phosphate
C. Fructose 1,6-bisphosphate
D. Glyceraldehyde 3-phosphate
E. 1,3-Bisphosphoglycerate
Correct Answer: C. Fructose 1,6-bisphosphate
Explanation:
Excess ATP from fatty acid oxidation inhibits phosphofructokinase-1 (PFK-1), the key rate-limiting enzyme of glycolysis. PFK-1 converts fructose 6-phosphate to fructose 1,6-bisphosphate, so its inhibition leads to a reduced concentration of this intermediate. The inhibitory effect of ATP on PFK-1 reduces the overall rate of glycolysis, conserving glucose when alternative energy sources like fatty acid oxidation are sufficient.
4. A 12-year-old boy presents with convulsions and is diagnosed with epilepsy after an EEG. He is started on benzodiazepine, which enhances the activity of GABA (gamma-aminobutyric acid). GABA is derived from glutamate. Which of the following reactions and coenzymes are involved in its synthesis?
A. Transamination, PLP
B. Decarboxylation, PLP
C. Deamination, PLP, and FMN
D. Hydroxylation, Vitamin C
E. Dehydrogenation, NAD⁺
Correct Answer: B. Decarboxylation, PLP
Explanation:
GABA is synthesized from glutamate via the enzyme glutamate decarboxylase (GAD), which catalyzes the decarboxylation of glutamate. This reaction requires pyridoxal phosphate (PLP), the active form of vitamin B6, as a coenzyme. PLP facilitates the removal of the carboxyl group from glutamate to form GABA, a key inhibitory neurotransmitter in the central nervous system. This pathway is critical in managing conditions like epilepsy, where GABAergic activity is enhanced to control convulsions.
5. An African-American couple gives birth to a boy who is exceptionally fair-skinned with nearly white hair and red pupils. A postnatal screen is likely to confirm a deficiency in which of the following enzymes?
A. Glutathione reductase
B. Glutathione peroxidase
C. Tyrosinase
D. Methionine synthase
E. Cystathionine beta-synthase
Correct Answer: C. Tyrosinase
Explanation:
The described features—fair skin, white hair, and red pupils—are characteristic of oculocutaneous albinism (OCA). This condition is commonly caused by a deficiency of tyrosinase, an enzyme required for the conversion of tyrosine to melanin in melanocytes. The lack of melanin leads to hypopigmentation of the skin, hair, and eyes, as well as red-appearing pupils due to the lack of pigment in the iris. Other enzymes listed are unrelated to pigmentation.
6. In a patient suspected of having arsenate poisoning, the production of which of the following compounds would be directly affected?
A. Pyruvate
B. 2,3-Bisphosphoglycerate
C. 2-Phosphoglycerate
D. 1,3-Bisphosphoglycerate
E. 3-Phosphoglycerate
Correct Answer: D. 1,3-Bisphosphoglycerate
Explanation:
Arsenate interferes with glycolysis by substituting for inorganic phosphate during the conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate, a reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase. Instead of forming 1,3-bisphosphoglycerate, an unstable arsenate compound is produced and quickly hydrolyzed, bypassing ATP generation in glycolysis. This disruption in 1,3-bisphosphoglycerate production is a hallmark of arsenate poisoning, leading to decreased energy production and metabolic dysfunction.
7. A 25-year-old athlete collapses after an intense sprinting session. Laboratory tests reveal elevated lactate levels and acidosis, consistent with anaerobic glycolysis due to oxygen deprivation during exercise. Which of the following glycolytic enzymes links glycolysis with the electron transport chain and justifies the lower energy yield in anaerobic conditions?
A. Phosphohexose isomerase
B. Glyceraldehyde 3-phosphate dehydrogenase
C. Lactate dehydrogenase
D. Phosphoglycerate kinase
E. Pyruvate kinase
Correct Answer: B. Glyceraldehyde 3-phosphate dehydrogenase
Explanation:
Glyceraldehyde 3-phosphate dehydrogenase catalyzes the oxidation of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate, coupling this process to the reduction of NAD⁺ to NADH. Under aerobic conditions, NADH enters the electron transport chain to generate ATP. However, in anaerobic conditions, the electron transport chain is inactive due to a lack of oxygen, and NADH is reoxidized to NAD⁺ by lactate dehydrogenase instead. This bypass results in a lower energy yield, as ATP generation via oxidative phosphorylation is absent.
8. The product of which of the following enzymes acts as a positive modifier of PFK-1?
A. Pyruvate carboxylase
B. Pyruvate dehydrogenase complex
C. PFK-2
D. Fructose 1,6-bisphosphatase
E. Fructose 2,6-bisphosphatase
Correct Answer: C. PFK-2
Explanation:
PFK-2 produces fructose 2,6-bisphosphate, a potent allosteric activator of PFK-1, the rate-limiting enzyme of glycolysis. Fructose 2,6-bisphosphate increases the affinity of PFK-1 for its substrate (fructose 6-phosphate), enhancing glycolysis, especially during high energy demands such as exercise. None of the other enzymes listed produce activators of PFK-1. Instead, enzymes like fructose 1,6-bisphosphatase oppose glycolysis by promoting gluconeogenesis. This regulatory interplay ensures metabolic flexibility under various conditions.
9. A 40-year-old woman complains of decreased energy, significant weight gain, and cold intolerance. Her family physician diagnoses her with hypothyroidism (low thyroid hormone levels). Which of the following is a precursor for thyroid hormone?
A. DOPA
B. Glutamine
C. Tyrosine
D. Tryptophan
E. Threonine
Correct Answer: C. Tyrosine
Explanation:
Tyrosine is the primary precursor for thyroid hormones (T3 and T4) produced in the thyroid gland. The process involves iodination of tyrosine residues within thyroglobulin to form monoiodotyrosine (MIT) and diiodotyrosine (DIT), which then combine to form triiodothyronine (T3) and thyroxine (T4). Other amino acids, such as tryptophan or threonine, are not involved in thyroid hormone synthesis. Tyrosine’s role is critical in maintaining proper thyroid function and metabolic regulation.
10. A 39-year-old woman has just given birth, and chorionic villus sampling revealed a defect in cystathionine-β-synthase in the newborn. If the mother was not properly treated during pregnancy, which of the following compounds would most likely be decreased in the infant’s blood at birth?
A. Valine
B. Methionine
C. Threonine
D. Glutamine
E. Cysteine
Correct Answer: E. Cysteine
Explanation:
Cystathionine-β-synthase (CBS) is an enzyme in the transsulfuration pathway that converts homocysteine and serine into cystathionine, which is further metabolized to produce cysteine. A defect in CBS leads to elevated homocysteine levels (homocystinuria) and decreased production of cysteine. Cysteine becomes an essential amino acid in this condition, and without proper maternal treatment (e.g., vitamin B6, B12, folate supplementation), the infant is born with low cysteine levels, which can contribute to metabolic and developmental complications. Methionine levels might also increase due to impaired homocysteine metabolism, but cysteine deficiency is the hallmark.
11. A 55-year-old man with cirrhosis of the liver suffers from impaired ammonia metabolism, leading to the accumulation of ammonia, which can damage the brain. Which of the following compounds is expected to be in the highest concentration in the brain as a result of ammonia detoxification?
A. Alpha-ketoglutarate
B. Glutamate
C. Glutamine
D. GABA
E. Asparagine
Correct Answer: C. Glutamine
Explanation:
In the brain, ammonia is detoxified by its incorporation into glutamine via the enzyme glutamine synthetase, which converts glutamate and ammonia to glutamine. This leads to an accumulation of glutamine in the brain, which can cause osmotic imbalances, astrocyte swelling, and contribute to hepatic encephalopathy. Levels of alpha-ketoglutarate and glutamate are reduced because they are consumed in the process of ammonia detoxification. GABA and asparagine are not directly involved in ammonia detoxification. Elevated glutamine is a hallmark of ammonia toxicity in the brain.
12. Which of the following enzymes is NADP⁺-dependent?
A. Pyruvate dehydrogenase
B. Alpha-ketoglutarate dehydrogenase
C. Lactate dehydrogenase
D. Glucose-6-phosphatase
E. Glucose-6-phosphate dehydrogenase
Correct Answer: E. Glucose-6-phosphate dehydrogenase
Explanation:
Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway (PPP) and is NADP⁺-dependent. It catalyzes the oxidation of glucose-6-phosphate to 6-phosphogluconolactone, reducing NADP⁺ to NADPH in the process. NADPH is critical for reductive biosynthesis and maintaining cellular redox balance, particularly in protecting cells from oxidative stress.
Other options involve NAD⁺ (e.g., pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and lactate dehydrogenase) or are unrelated to redox reactions (e.g., glucose-6-phosphatase).
13. Which of the following enzymes of the HMP pathway requires TPP (thiamine pyrophosphate) as a coenzyme?
A. Glucose-6-phosphate dehydrogenase
B. Transaldolase
C. Transketolase
D. 6-phosphogluconate dehydrogenase
E. Gluconolactone hydrolase
Correct Answer: C. Transketolase
Explanation:
Transketolase, an enzyme of the HMP shunt (pentose phosphate pathway), requires TPP (thiamine pyrophosphate) as a coenzyme. It catalyzes the transfer of two-carbon units from ketose donors to aldose acceptors, facilitating the interconversion of sugars in the non-oxidative phase of the pathway.
Other enzymes listed, such as glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, are involved in the oxidative phase and do not require TPP. Transaldolase, although part of the non-oxidative phase, does not use TPP as a coenzyme.
14. A breastfed infant presents with frequent vomiting, weight loss, jaundice, hepatomegaly, and bilateral cataracts. What is the most likely cause of these symptoms?
A. Galactosemia
B. Von Gierke’s disease
C. Juvenile diabetes mellitus
D. Hereditary fructose intolerance
E. Homocystinuria
Correct Answer: A. Galactosemia
Explanation:
The symptoms described—vomiting, weight loss, jaundice, hepatomegaly, and cataracts—are characteristic of classic galactosemia, a disorder caused by a deficiency in galactose-1-phosphate uridyltransferase (GALT). This leads to the accumulation of galactose-1-phosphate and galactitol, which are toxic to tissues:
• Cataracts result from galactitol accumulation in the lens.
• Jaundice and hepatomegaly are due to liver dysfunction caused by galactose-1-phosphate toxicity.
Early diagnosis and the elimination of galactose (found in breast milk and formula) from the diet are essential to prevent further complications.
Other conditions, such as von Gierke’s disease (glycogen storage disorder), hereditary fructose intolerance, or diabetes, do not specifically align with this combination of symptoms in a breastfed infant. Homocystinuria primarily affects connective tissue, not the liver or eyes, in this way.
15. Which of the following generates free glucose during the enzymatic breakdown of glycogen in skeletal muscles?
A. Phosphorylase
B. α-1-6-amyloglucosidase
C. Debranching enzyme
D. Glucose-6-phosphatase
E. Alpha-amylase
Correct Answer: B. α-1,6-Amyloglucosidase
Explanation:
The α-1,6-amyloglucosidase activity, a component of the debranching enzyme, cleaves the α-1,6 glycosidic bond at the branch points of glycogen. This reaction releases free glucose, making it the only step in glycogenolysis where free glucose is generated, even in skeletal muscle.
Although the debranching enzyme itself has multiple activities, the specific subactivity that generates free glucose is the α-1,6-amyloglucosidase function, which is why this option is the most precise.
16. A 3-month-old infant presents with hepatosplenomegaly and failure to thrive. A liver biopsy reveals glycogen with an abnormal, amylopectin-like structure with long outer chains and missing branches. Which of the following enzymes is most likely deficient?
A. Alpha-Amylase
B. Branching enzyme
C. Debranching enzyme
D. Glycogen phosphorylase
E. Glucose-6-phosphatase
Correct Answer: B. Branching enzyme
Explanation:
The described condition is consistent with glycogen storage disease type IV (Andersen disease), caused by a deficiency in the branching enzyme (glucosyl-4:6-transferase). This enzyme introduces α-1,6 glycosidic bonds into the glycogen structure, creating branches. Its deficiency results in glycogen with an abnormal amylopectin-like structure with reduced branching, making it less soluble and prone to accumulation in tissues such as the liver and spleen. This leads to hepatosplenomegaly, failure to thrive, and progressive organ damage.
Other enzymes listed, such as glycogen phosphorylase and debranching enzyme, are involved in glycogen breakdown, while glucose-6-phosphatase is related to glucose release, not glycogen structure. Alpha-amylase is unrelated to glycogen metabolism.
17. Which of the following enzymes of glycogen metabolism is absent in skeletal muscle?
A. Phosphorylase
B. α-1,6-Amyloglucosidase
C. Debranching enzyme
D. Glucose-6-phosphatase
E. Phosphoglucomutase
Correct Answer: D. Glucose-6-phosphatase
Explanation:
Glucose-6-phosphatase is absent in skeletal muscle. This enzyme is responsible for converting glucose-6-phosphate to free glucose, a step required for glucose release into the bloodstream. It is present in the liver and kidneys, where glycogen breakdown contributes to maintaining blood glucose levels.
In skeletal muscle, glycogen breakdown provides glucose-6-phosphate for glycolysis to meet the energy demands of muscle cells, not for blood glucose regulation. The other listed enzymes are present and actively participate in glycogen metabolism within skeletal muscle.
18. McArdle’s syndrome causes muscle cramps and fatigue with increased muscle glycogen. Which of the following enzymes is deficient?
A. Hepatic hexokinase
B. Muscle phosphorylase
C. Muscle debranching enzyme
D. Muscle hexokinase
E. Muscle phosphofructokinase
Correct Answer: B. Muscle phosphorylase
Explanation:
McArdle’s syndrome (Glycogen Storage Disease Type V) is caused by a deficiency of muscle glycogen phosphorylase, an enzyme responsible for breaking down glycogen into glucose-1-phosphate in skeletal muscle. This leads to:
• Accumulation of glycogen in muscle tissue.
• Inability to generate sufficient glucose for glycolysis during exercise, resulting in muscle cramps, fatigue, and, in severe cases, rhabdomyolysis.
Other enzymes, such as the debranching enzyme, hexokinase, or phosphofructokinase, are not involved in this specific disorder. Hepatic hexokinase is unrelated, as McArdle’s syndrome affects skeletal muscle, not the liver.
19. Von Gierke’s disease is characterized by the deficiency of which of the following enzymes?
A. Phosphorylase
B. Glucose-6-phosphatase
C. Debranching enzyme
D. Phosphoglucomutase
E. Branching enzyme
Correct Answer: B. Glucose-6-phosphatase
Explanation:
Von Gierke’s disease (Glycogen Storage Disease Type I) is caused by a deficiency of glucose-6-phosphatase, an enzyme responsible for converting glucose-6-phosphate to free glucose in the liver. This defect prevents the liver from releasing glucose into the bloodstream during fasting, leading to:
• Hypoglycemia (low blood glucose levels).
• Hepatomegaly (enlarged liver) due to glycogen accumulation.
• Lactic acidosis, hyperuricemia, and hyperlipidemia due to impaired metabolic pathways.
Other enzymes listed are involved in glycogen metabolism but are not deficient in von Gierke’s disease. For instance, branching enzyme deficiency causes Andersen disease, and debranching enzyme deficiency causes Cori disease.
20. The diet of a child suffering from Maple Syrup Urine Disease (MSUD) should be low in which of the following amino acids?
A. Branched-chain amino acids
B. Phenylalanine
C. Methionine
D. Tryptophan
E. Glycine
Correct Answer: A. Branched-chain amino acids
Explanation:
Maple Syrup Urine Disease (MSUD) is caused by a deficiency in the branched-chain α-ketoacid dehydrogenase (BCKD) complex, which is responsible for the metabolism of branched-chain amino acids (BCAAs): leucine, isoleucine, and valine. Affected individuals cannot properly break down these amino acids, leading to their accumulation and associated toxic metabolites, which cause symptoms like sweet-smelling urine, lethargy, developmental delay, and neurotoxicity.
To manage MSUD, the diet must be low in BCAAs while ensuring enough is provided to meet essential requirements for growth and development. Other amino acids, such as phenylalanine, methionine, tryptophan, or glycine, are not directly involved in this condition.
21. A child with tall stature, loose joints, and detached retinas is found to have a mutation in collagen. Which of the following amino acids is the recurring amino acid most likely to be altered in mutations that distort collagen molecules?
A. Glycine
B. Tyrosine
C. Tryptophan
D. Tyrosine
E. Serine
Correct Answer: A. Glycine
Explanation:
Glycine is the most frequently recurring amino acid in collagen, appearing every third residue in the collagen triple helix structure. Its small size is critical for the tight packing and stability of the triple helix. Mutations that replace glycine with bulkier amino acids disrupt the structure of the collagen molecule, leading to conditions such as Ehlers-Danlos syndrome or other connective tissue disorders.
The other amino acids listed are not integral to the repeating glycine-X-Y sequence of collagen and do not play as significant a role in its structural stability.
