A 45-year-old man with poorly controlled diabetes presents with increased thirst, frequent urination, nausea, vomiting, rapid breathing, and a fruity breath odor characteristic of acetone. His arterial blood gas shows metabolic acidosis with respiratory compensation. Which hormonal change is most likely contributing to his condition?
A 3-month-old girl with seizures, severe hypoglycemia, hyperlipidemia, lactic acidosis, and hepatomegaly is diagnosed with Von Gierke disease. This condition is caused by a deficiency in glucose-6-phosphatase. Where does the enzyme defect primarily impair metabolic function?
A 7-year-old boy develops severe abdominal cramps after eating fatty meals and is found to have lipoprotein lipase (LPL) deficiency. Where is LPL normally most active in processing dietary fats?
A 47-year-old man presents with acute monoarticular arthritis in his ankle and a history of recurrent flank pain. Synovial fluid analysis reveals needle-shaped, negatively birefringent crystals. What is the biochemical basis of the medication commonly used for chronic management of this condition?
In knockout mice lacking phenylethanolamine-N-methyltransferase (PNMT), which step in catecholamine biosynthesis is directly blocked?
A child exhibiting developmental delay, spasticity, compulsive self-mutilation (biting fingers/lips), arthritis, and renal failure likely suffers from Lesch-Nyhan syndrome. What is the inheritance pattern of this disorder?
An infant develops severe hypoglycemia, vomiting, lethargy, and liver dysfunction shortly after fruits (containing fructose) are introduced into the diet. These symptoms are characteristic of hereditary fructose intolerance (HFI). What metabolite accumulates and causes toxicity in HFI?
An infant presents with lethargy, seizures, vomiting, and acidosis after a period of fasting or illness. Labs show hypoglycemia, low ketone levels, and elevated C8-C10 acylcarnitines, indicating MCAD deficiency. Why does hyperammonemia occur in this condition?
A 26-year-old woman with a family history of hemolytic anemia and parental consanguinity is diagnosed with pyruvate kinase (PK) deficiency. How does this enzyme deficiency lead to red blood cell lysis?
A man following a strict low-carbohydrate diet relies on alternative fuels. While fatty acids are broken down for energy, they cannot be converted directly into glucose. However, the glycerol backbone released from triglyceride breakdown can be used for gluconeogenesis. Which enzyme initiates the entry of glycerol into the gluconeogenic pathway?
A child diagnosed with orotic aciduria presents with megaloblastic anemia unresponsive to B12/folate and orotic acid crystals in the urine. Treatment with uridine is effective. Why does uridine administration alleviate the symptoms?
A neonate develops severe neurological symptoms and ketonuria. The condition is identified as Maple Syrup Urine Disease (MSUD), caused by a deficiency in the branched-chain ketoacid dehydrogenase complex. Which amino acids must be restricted in the diet?
A jaundiced neonate requires phototherapy. This treatment effectively breaks down bilirubin but can also degrade a specific vitamin, necessitating supplementation. Which vitamin is susceptible to degradation by phototherapy?
A 1-year-old boy presents with severe hypotonia, difficulty feeding, progressive dyspnea, hepatomegaly, and cardiomegaly, consistent with Pompe disease. What is the subcellular location of the deficient enzyme in this disorder?
A healthy 2-year-old girl undergoing a routine check-up has urinalysis positive for a reducing substance, but negative for glucose. Further testing confirms the substance is fructose. She is asymptomatic and meeting developmental milestones. What is the most likely diagnosis?
An African-American man develops hemolytic anemia after taking primaquine for malaria prophylaxis. This is a classic presentation of Glucose-6-phosphate dehydrogenase (G6PD) deficiency. What is the primary biochemical consequence of G6PD deficiency that predisposes red blood cells to hemolysis?
Chronic alcohol consumption leads to a significant increase in the NADH/NAD+ ratio in hepatocytes. How does this altered ratio affect the metabolic fate of pyruvate?
Six hours after a meal, blood glucose homeostasis is maintained primarily by hepatic glucose production. Glucagon signaling plays a key role. Which enzyme involved in glycogen metabolism is activated by glucagon-mediated phosphorylation?
Malnourished children presenting with edema, enlarged fatty livers, skin lesions, and apathy are likely suffering from Kwashiorkor, a form of protein-energy malnutrition. Which of the following is an essential amino acid that must be obtained from the diet?
Pentavalent arsenic (arsenate) disrupts ATP production during glycolysis. Which specific reaction's ATP yield is eliminated by arsenate?
A chronic alcoholic presents with confusion, ataxia, and ophthalmoplegia (Wernicke encephalopathy), which improves, but he is left with severe memory deficits and confabulation (Korsakoff syndrome). Thiamine (Vitamin B1) deficiency underlies this condition. Which enzyme's activity is critically dependent on a thiamine-derived cofactor?
In analyzing enzyme kinetics using a Lineweaver-Burk plot (1/v vs 1/[S]), what does the intercept on the y-axis represent?
A 47-year-old man with chronic alcoholism develops Wernicke-Korsakoff syndrome due to thiamine deficiency. Besides pyruvate dehydrogenase and transketolase, which other crucial mitochondrial enzyme complex requires thiamine pyrophosphate (TPP) as a cofactor?
A 15-month-old child with progressive neurologic deterioration, hepatosplenomegaly, and retinal pallor sparing the macula is diagnosed with Niemann-Pick disease Type A. What substance accumulates in lysosomes due to the enzyme deficiency?
A patient is found to have a deficiency in gamma-glutamyltranspeptidase (GGT), leading to elevated urine glutathione levels and neurological symptoms. What is the primary role of GGT in the gamma-glutamyl cycle?
Citrate levels increase in the cytosol when the citric acid cycle activity slows or when cellular energy levels are high. Besides inhibiting phosphofructokinase-1, citrate acts as an allosteric activator for which key enzyme in fatty acid synthesis?
An infant develops jaundice, hepatomegaly, failure to thrive, and cataracts after starting milk feedings. Classic galactosemia is diagnosed. What is the primary treatment strategy?
A child presents with hypoketotic hypoglycemia, muscle weakness, and cardiomyopathy. Labs show elevated long-chain acylcarnitines. This pattern suggests a defect in fatty acid beta-oxidation, such as LCAD deficiency. What is the characteristic metabolic state during fasting in these disorders?
A 24-year-old woman experiences severe muscle cramps and myoglobinuria after strenuous exercise, but her serum lactate levels do not increase appropriately. This presentation is typical of McArdle disease. Which tissue is primarily affected?
A newborn with jaundice has glycogen storage disease type IV (Andersen disease). Analysis of the glycogen structure reveals an abnormally high ratio of glucose-1-phosphate to free glucose upon enzymatic digestion. What structural abnormality does this indicate?
When performing an enzyme assay to determine the amount of enzyme present in a sample, it is ideal to ensure the reaction rate is independent of substrate concentration. Under what condition is the enzyme's reaction rate primarily dependent only on enzyme concentration?
The activity of the pyruvate dehydrogenase (PDH) complex increases significantly during aerobic exercise. Which intracellular ion plays a key role in activating PDH phosphatase, thereby promoting the active, dephosphorylated state of PDH?
A patient receiving broad-spectrum antibiotics for 4 weeks develops easy bruising and prolonged prothrombin time (PT). This is likely due to a deficiency in Vitamin K, affecting the synthesis of functional clotting factors. Which specific post-translational modification, dependent on Vitamin K, is impaired?
A pregnant woman with phenylketonuria (PKU) has poorly controlled, high serum phenylalanine levels during her first trimester. What is the primary risk to her fetus?
Cocaine abuse can lead to coronary vasospasm and myocardial ischemia, resulting in contraction band necrosis. Under these ischemic conditions, what metabolic pathway becomes the primary source of ATP for the affected myocardial cells?
A 64-year-old man presents with a painful, swollen right knee. Arthrocentesis reveals cloudy fluid with numerous neutrophils and strongly negatively birefringent, needle-shaped crystals. This presentation is classic for gout. What is the chemical composition of these crystals?
Carnitine is essential for the transport of long-chain fatty acids into the mitochondria for beta-oxidation. From which two amino acids is carnitine endogenously synthesized?
Nitric oxide (NO) released from endothelial cells causes vasodilation by acting on adjacent smooth muscle cells. What is the immediate downstream effect of NO within the smooth muscle cell?
Metabolic pathways are compartmentalized within the cell. Which of the following enzymes is correctly localized to the mitochondrial matrix?
Chylomicrons, synthesized in the intestine after a fatty meal, decrease in size as they circulate. This is due to the action of lipoprotein lipase (LPL). What molecule, acquired from HDL in circulation, is necessary to activate LPL?
Gluconeogenesis bypasses the irreversible glycolytic step catalyzed by phosphofructokinase-1 (PFK-1). Which enzyme catalyzes the reverse reaction in gluconeogenesis, converting fructose-1,6-bisphosphate to fructose-6-phosphate?
A child presents with tall stature, long limbs, downward dislocation of the lenses (ectopia lentis), developmental delay, and a history of thromboembolic events. These features are highly suggestive of classic homocystinuria. Which enzyme is typically deficient?
A 14-year-old girl experiences painful leg cramps and fatigue shortly after beginning exercise. A key diagnostic finding in McArdle disease (myophosphorylase deficiency) is the failure to produce what substance in the blood during anaerobic exercise?
Lead poisoning inhibits heme synthesis, contributing to microcytic anemia. Besides ALA dehydratase, which other enzyme in the heme synthesis pathway is inhibited by lead?
During intense anaerobic exercise, pyruvate is converted to lactate in skeletal muscle. What is the primary purpose of this reaction catalyzed by lactate dehydrogenase (LDH)?
Hemorrhagic disease of the newborn can occur due to Vitamin K deficiency. Which clotting factor, dependent on Vitamin K for its synthesis, has the shortest half-life and is therefore depleted most rapidly, leading to an early elevation of the prothrombin time (PT)?
Familial Hypocalciuric Hypercalcemia (FHH) is typically caused by an inactivating mutation in the calcium-sensing receptor (CaSR) gene. What pattern of laboratory findings differentiates FHH from primary hyperparathyroidism (e.g., due to an adenoma)?
Gallstones in patients with sickle cell anemia are typically composed primarily of calcium bilirubinate. What is the underlying reason for the formation of these particular stones?
A young boy emigrating from a region where polished rice is a dietary staple presents with signs of high-output cardiac failure (dilated cardiomyopathy). This clinical picture, known as 'wet beriberi', is caused by a deficiency in which vitamin?
Following ingestion of glucose and subsequent insulin release, glucose uptake into skeletal muscle cells increases significantly. Which glucose transporter isoform is responsible for this insulin-stimulated uptake?
Pyruvate carboxylase deficiency leads to impaired conversion of pyruvate to oxaloacetate. Besides its role in replenishing TCA cycle intermediates (anaplerosis), pyruvate carboxylase is essential for which other major metabolic pathway?
Ornithine transcarbamylase (OTC) deficiency typically presents in male neonates with hyperammonemia, lethargy, and coma. A key finding distinguishing OTC deficiency from carbamoyl phosphate synthetase I (CPS I) deficiency is the presence of:
Tay-Sachs disease and Niemann-Pick disease Type A are lysosomal storage diseases with increased prevalence in the Ashkenazi Jewish population, both presenting with progressive neurodegeneration in infancy and a potential cherry-red spot on fundoscopy. What clinical finding is typically present in Niemann-Pick disease but absent in Tay-Sachs disease?
A malnourished alcoholic patient presents with perifollicular hemorrhages, ecchymoses, bleeding gums, and poor wound healing. These findings are characteristic of scurvy. The underlying biochemical defect involves impaired synthesis of which protein?
A child presents with failure to thrive, steatorrhea, night blindness, ataxia, and acanthocytes on peripheral blood smear. This constellation suggests abetalipoproteinemia. Which class of lipoproteins is characteristically absent from the plasma in this condition?
After several days of fasting, the brain adapts to utilize alternative fuel sources to spare glucose. What becomes the predominant fuel source for the brain during prolonged starvation?
A 6-month-old infant of Ashkenazi Jewish descent presents with progressive neurodegeneration, loss of motor skills, increased startle response, and a cherry-red spot on macular examination, but no hepatosplenomegaly. This is consistent with Tay-Sachs disease. What enzyme is deficient?
A patient with episodic hypertension, palpitations, and headaches is found to have an adrenal pheochromocytoma secreting excess catecholamines. Which enzyme catalyzes the rate-limiting step in the synthesis of these catecholamines from their amino acid precursor?
A patient known to have Acute Intermittent Porphyria (AIP) develops severe abdominal pain, tachycardia, hypertension, and neurological symptoms after starting treatment with phenobarbital for seizures. What is the biochemical basis for drug precipitation of AIP attacks?