Biochemistry Flashcards

In order to determine the rate of DNA synthesis in various mammalian tissues, the administration of which of the following labeled substances would be most specific in labeling DNA?

Answer: Thymidine

DNA contains the nitrogenous base thymine, while RNA contains uracil instead of thymine. Therefore, labeled thymidine, a deoxyribonucleoside containing thymine, is specifically incorporated into newly synthesized DNA strands during replication. This makes thymidine the most specific substance for measuring DNA synthesis without inadvertently labeling RNA.

A 2-year-old boy who recently emigrated from Somalia is brought to the physician because of a 1-day history of pain of his arms and legs. Physical examination shows pale mucous membranes and hepatosplenomegaly. Laboratory studies show a hemoglobin concentration of 8 g/dL. A peripheral blood smear shows sickle cells. Genetic analyses show a point mutation in the β-globin gene leading to a change of a GAG codon (glutamate) to a GUG codon (valine). Which of the following anticodons is most likely in the tRNA for valine?

Answer: CAC

The mRNA codon for valine in this patient's sickle cell mutation is GUG. Transfer RNA (tRNA) anticodons are complementary to mRNA codons, following standard base-pairing rules (G with C, U with A). Therefore, the anticodon that would pair with the GUG codon is CAC.

Which of the following post-translational modifications is most likely to be found on a cyclin B protein that is targeted for degradation?

Answer: Ubiquitinated lysine residues

The degradation of cell cycle regulatory proteins, such as cyclin B, is a tightly controlled process essential for proper cell cycle progression and exit from mitosis. Proteins targeted for degradation via the ubiquitin-proteasome system are covalently tagged with multiple ubiquitin molecules, typically on lysine residues. This polyubiquitin chain serves as a signal for recognition and breakdown by the proteasome.

A previously healthy 16-year-old girl is brought to the physician because of abdominal cramps, bloating, and loose stools for 6 months. These symptoms began after she ingested skim milk in an attempt to lose weight. She is at the 50th percentile for height and 75th percentile for weight. Physical examination shows no abnormalities. Stool studies show a 3+ Clinitest reagent response and pH of 5. After the patient ingests milk, there is an increased hydrogen concentration in expired air. A deficiency of which of the following enzyme activities is the most likely cause of the gastrointestinal symptoms in this patient?

Answer: Lactase

The patient's symptoms (abdominal cramps, bloating, loose stools) after consuming milk, along with a positive stool Clinitest, acidic stool pH, and increased expired hydrogen, are classic signs of lactose intolerance. This condition results from a deficiency in lactase, the enzyme responsible for breaking down lactose (milk sugar) into glucose and galactose in the small intestine. Undigested lactose ferments in the colon, producing gas and acidic byproducts.

A married couple is screened to assess the risk for Gaucher disease in their children. The activities of glucocerebrosidase in the sera of the mother and father are 45% and 55%, respectively, of the reference value. The couple has one child. Which of the following is the probability of the child possessing one or more alleles of the Gaucher mutation?

Answer: 0.75

Gaucher disease is an autosomal recessive disorder. Since both parents have reduced glucocerebrosidase activity (45% and 55% of normal), they are both carriers (heterozygotes) for the Gaucher mutation. When two carriers (Gg x Gg) have a child, there is a 25% probability of the child being unaffected (GG), a 50% probability of being a carrier (Gg), and a 25% probability of being affected (gg). Therefore, the probability of the child possessing one or more alleles of the Gaucher mutation (Gg or gg) is 50% + 25% = 75%.

The release of epinephrine from the chromaffin granules of the adrenal medulla into the bloodstream in response to neural stimulation is mediated by which of the following?

Answer: Acetylcholine

The adrenal medulla is directly innervated by preganglionic sympathetic neurons. These neurons release acetylcholine (ACh) at their terminals. ACh then binds to nicotinic acetylcholine receptors on the chromaffin cells of the adrenal medulla, triggering their depolarization and the subsequent release of catecholamines, primarily epinephrine, into the bloodstream.

During normal screening for phenylketonuria, a male newborn has a serum phenylalanine concentration of 35 mg/dL (greater than 20 mg/dL is considered a positive test). Signs of tyrosine deficiency also are apparent. Enzymatic analysis using cultured fibroblasts, obtained after circumcision, shows normal activity of phenylalanine hydroxylase. A possible explanation for these findings is a deficiency in function of which of the following coenzymes?

Answer: Biopterin

While classical phenylketonuria (PKU) is caused by a deficiency in phenylalanine hydroxylase (PAH), this patient has normal PAH activity. Therefore, the hyperphenylalaninemia and tyrosine deficiency are most likely due to a defect in tetrahydrobiopterin (BH4) metabolism. BH4 is an essential cofactor for phenylalanine hydroxylase, and its deficiency prevents the conversion of phenylalanine to tyrosine, leading to a form of atypical PKU.

A 2-year-old boy with mental retardation has chewed the tips of his fingers on both hands and a portion of his lower lip. His serum uric acid concentration is increased, and he has a history of uric acid renal calculi. His 5-year-old brother has similar findings. Which of the following abnormal enzyme activities is the most likely cause of these findings?

Answer: Decreased hypoxanthine-guanine phosphoribosyltransferase

The patient's symptoms, including mental retardation, self-mutilation, hyperuricemia, and uric acid renal calculi, along with a family history, are classic for Lesch-Nyhan syndrome. This X-linked recessive disorder is caused by a deficiency in hypoxanthine-guanine phosphoribosyltransferase (HGPRT). HGPRT is crucial for the purine salvage pathway, and its deficiency leads to increased purine degradation and overproduction of uric acid.

A 14-year-old girl is brought to the physician because of a recent growth spurt of 15 cm (6 in) during the past year. She also has had increasing fatigue and palpitations during this period. Her paternal aunt has a history of palpitations and severe myopia. She is at the 95th percentile for height and 50th percentile for weight. Physical examination shows a long, thin face. Ophthalmologic examination shows dislocated lenses. Cardiac examination shows a hyperdynamic precordium with early click and systolic murmur. Echocardiography shows an enlarged aortic root and mitral valve prolapse. Abnormal synthesis of which of the following proteins is the most likely cause of this patient’s disorder?

Answer: Fibrillin-1

The patient's tall stature, long thin face, dislocated lenses, and cardiovascular abnormalities like an enlarged aortic root and mitral valve prolapse are characteristic features of Marfan syndrome. This autosomal dominant disorder results from a mutation in the *FBN1* gene, which encodes fibrillin-1. Fibrillin-1 is a key component of elastic fibers, and its abnormal synthesis leads to weakened connective tissue throughout the body, particularly affecting the skeletal, ocular, and cardiovascular systems.

Native collagen is composed almost entirely of which of the following types of structures?

Answer: Triple helix

Native collagen is predominantly structured as a triple helix, formed by three polypeptide alpha chains wound around each other. This unique conformation, rich in glycine, proline, and hydroxyproline, provides collagen with its remarkable tensile strength and structural integrity. This triple-helical arrangement is fundamental to collagen's role as the primary structural protein in connective tissues.

An otherwise healthy 20-year-old woman of Mediterranean descent is given sulfamethoxazole to treat a bladder infection. Three days after beginning the antibiotic regimen, the patient has moderately severe jaundice and dark urine. Pain with urination and a low-grade fever have resolved. Her hematocrit is 20%. Substantial numbers of erythrocytes contain Heinz bodies. Her condition worsens until day 6 of antibiotic therapy, when it begins to resolve. Symptoms are completely gone by day 9 of continued antibiotic therapy. Which of the following conditions is the most likely explanation for these findings?

Answer: Glucose-6-phosphate dehydrogenase deficiency

The patient's hemolytic anemia (jaundice, dark urine, low hematocrit) with Heinz bodies, triggered by an oxidative drug like sulfamethoxazole, especially in a person of Mediterranean descent, strongly indicates glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD is essential for producing NADPH, which protects red blood cells from oxidative damage. Without sufficient G6PD, oxidative stress leads to hemoglobin denaturation (forming Heinz bodies) and subsequent hemolysis.

A 45-year-old woman has the sudden onset of severe headaches. During one of these episodes, her blood pressure is 190/115 mm Hg. Her usual blood pressure is 130/90 mm Hg. Her sister had similar episodes several years ago. Urinalysis shows increased concentrations of metanephrine and vanillylmandelic acid. The patient is most likely to have a neoplasm that secretes which of the following?

Answer: Epinephrine

The patient's paroxysmal hypertension, severe headaches, and elevated urinary metanephrines and vanillylmandelic acid (VMA) are classic indicators of a pheochromocytoma. This tumor typically arises from chromaffin cells in the adrenal medulla and secretes excessive amounts of catecholamines, primarily epinephrine and norepinephrine. The increased breakdown products (metanephrines and VMA) confirm the overproduction of these hormones.

An inherited disorder of carbohydrate metabolism is characterized by an abnormally increased concentration of hepatic glycogen with normal structure and no detectable increase in serum glucose concentration after oral administration of fructose. These two observations suggest that the disease is a result of the absence of which of the following enzymes?

Answer: Glucose-6-phosphatase

The presence of increased hepatic glycogen with normal structure, combined with no increase in serum glucose after oral fructose, points to a defect in the final step of glucose release from the liver. Glucose-6-phosphatase is the enzyme responsible for dephosphorylating glucose-6-phosphate to free glucose, allowing it to exit the liver. Its absence traps glucose-6-phosphate in the liver, leading to glycogen accumulation and an inability to raise blood glucose from precursors like fructose, characteristic of Von Gierke disease.

A 15-year-old girl limits her diet to carrots, tomatoes, green vegetables, bread, pasta, rice, and skim milk. She has an increased risk for vitamin A deficiency because its absorption requires the presence of which of the following?

Answer: Triglyceride

Vitamin A is a fat-soluble vitamin, and its absorption is highly dependent on the presence of dietary fat. Triglycerides are the primary form of fat in the diet and are crucial for stimulating bile acid secretion and chylomicron formation, which are necessary for the emulsification, digestion, and absorption of fat-soluble vitamins. A diet severely restricted in fat, such as one including only skim milk and no other fat sources, would significantly impair vitamin A absorption.

An increased concentration of fructose 2,6-bisphosphate in hepatocytes will have a positive regulatory effect on which of the following?

Answer: Glycolysis and phosphofructokinase 1

Fructose 2,6-bisphosphate is a potent allosteric activator of phosphofructokinase-1 (PFK-1), the rate-limiting enzyme in glycolysis. By increasing PFK-1 activity, it promotes the conversion of fructose-6-phosphate to fructose 1,6-bisphosphate, thereby stimulating the glycolytic pathway. Conversely, it inhibits fructose 1,6-bisphosphatase, an enzyme in gluconeogenesis, ensuring that glycolysis is favored when its concentration is high.

During the processing of particular N-linked glycoproteins, residues of mannose 6-phosphate are generated. Which of the following proteins is most likely to undergo this step in processing?

Answer: Lysosomal α-fucosidase

Mannose 6-phosphate (M6P) is a specific tag added to N-linked glycoproteins destined for lysosomes. This M6P tag acts as a signal, allowing these proteins to bind to M6P receptors in the Golgi apparatus, which then package them into vesicles for transport to lysosomes. Lysosomal α-fucosidase is a lysosomal enzyme, and its proper targeting to the lysosome requires this M6P modification.

A 65-year-old man with coronary artery disease comes to the physician for a follow-up examination. He is 183 cm (6 ft) tall and weighs 84 kg (185 lb); BMI is 25 kg/m2 . His blood pressure is 130/80 mm Hg. The lungs are clear to auscultation. Cardiac examination shows no point of maximal impulse. Serum studies show a glucose concentration of 95 mg/dL and homocysteine concentration of 19.3 μmol/L (N=5–15). Serum lipid concentrations are within the reference range. Which of the following amino acids is most likely to be decreased in this patient?

Answer: Methionine

Homocysteine is an intermediate in methionine metabolism. Elevated homocysteine levels often result from deficiencies in enzymes or cofactors (like folate, vitamin B12, or vitamin B6) involved in its remethylation back to methionine or its transsulfuration to cysteine. If homocysteine cannot be efficiently converted back to methionine, then methionine levels would likely be decreased as it is the product of this crucial metabolic pathway.

Which of the following is required to transport fatty acids across the inner mitochondrial membrane?

Answer: Carnitine

Long-chain fatty acids cannot directly cross the inner mitochondrial membrane for beta-oxidation. They require a specialized transport system involving carnitine. Fatty acids are transferred to carnitine by carnitine palmitoyltransferase I (CPT-I) to form acylcarnitine, which is then transported across the inner mitochondrial membrane by the carnitine-acylcarnitine translocase. Inside the mitochondrial matrix, CPT-II transfers the fatty acid back to CoA, releasing carnitine and allowing beta-oxidation to proceed.

Failure to bind LDL to its receptor results in uncontrolled synthesis of cholesterol. This occurs because synthesis of which of the following enzymes is not repressed?

Answer: 3-Hydroxy-3-methylglutaryl (HMG)-CoA reductase

When LDL binding and uptake are impaired, cells perceive a lack of intracellular cholesterol, leading to increased *de novo* cholesterol synthesis. 3-Hydroxy-3-methylglutaryl (HMG)-CoA reductase is the rate-limiting enzyme in cholesterol biosynthesis. Its activity is normally repressed by high intracellular cholesterol. Therefore, a failure of LDL uptake would prevent this repression, leading to uncontrolled synthesis of cholesterol by HMG-CoA reductase.

A 67-year-old man has a restricted diet that includes no fresh citrus fruits or leafy green vegetables. His teeth are loose and his gums bleed easily. This patient’s disorder most likely results from a defect in collagen synthesis that involves which of the following amino acids?

Answer: Hydroxyproline

The patient's symptoms of loose teeth and bleeding gums, combined with a diet lacking fresh citrus fruits and leafy green vegetables, are classic signs of scurvy, caused by vitamin C deficiency. Vitamin C is a crucial cofactor for prolyl hydroxylase and lysyl hydroxylase, enzymes responsible for hydroxylating proline and lysine residues in collagen. Hydroxyproline is essential for forming stable cross-links within the collagen triple helix, and its deficiency leads to unstable collagen and connective tissue defects.