Metabolism

Metabolism US Medical PG Question 1: Organ that can utilize glucose, fatty acids and ketone bodies is:

• A. Liver
• B. Brain
• C. Skeletal muscle (Correct Answer)
• D. RBC

Metabolism Explanation: ***Skeletal muscle*** - Skeletal muscle is highly adaptable and can utilize **glucose**, **fatty acids (FAs)**, and **ketone bodies** as fuel sources, especially during prolonged exercise or starvation. - Its metabolic flexibility allows it to switch between these substrates depending on their availability and the body's energy demands. *Liver* - The liver is central to metabolism but primarily **produces ketone bodies** from fatty acids rather than utilizing them as a major fuel source for its own energy needs. - While it uses glucose and FAs, its role in ketone body metabolism is largely synthetic. *Brain* - The brain preferentially uses **glucose** as its primary fuel. - During prolonged starvation, it can adapt to utilize **ketone bodies** as an alternative fuel source, but it does not significantly use fatty acids directly. *RBC* - Red blood cells (RBCs) lack mitochondria and therefore rely exclusively on **anaerobic glycolysis** for energy, metabolizing only **glucose**. - They cannot utilize fatty acids or ketone bodies.

Metabolism US Medical PG Question 2: A 20-year-old man presents with muscle cramps and myoglobinuria after moderate exercise. He reports that he gets a 'second wind' if he rests briefly during exercise and then continues. Ischemic forearm exercise test shows no rise in venous lactate. Muscle biopsy reveals periodic acid-Schiff (PAS)-positive material. Apply these findings to identify the underlying enzyme deficiency.

• A. Phosphofructokinase deficiency
• B. Debranching enzyme deficiency
• C. Muscle phosphorylase deficiency (Correct Answer)
• D. Branching enzyme deficiency
• E. Phosphorylase kinase deficiency

Metabolism Explanation: ***Muscle phosphorylase deficiency*** - The presence of the **'second wind' phenomenon** and **exercise-induced myoglobinuria** are hallmark features of **McArdle disease** (GSD Type V), caused by a deficiency in myophosphorylase. - An **ischemic forearm test** showing **no rise in venous lactate** combined with **PAS-positive** glycogen accumulation in muscle confirms the inability to break down glycogen into glucose-1-phosphate. *Phosphofructokinase deficiency* - Also known as **Tarui disease** (GSD Type VII), it presents similarly to McArdle disease but often includes **hemolytic anemia** due to enzyme deficiency in RBCs. - Patients with this deficiency do not typically exhibit the **'second wind' phenomenon** and may experience a 'vicious circle' where glucose intake worsens symptoms. *Debranching enzyme deficiency* - Deficiency in **alpha-1,6-glucosidase** leads to **Cori disease** (GSD Type III), which primarily presents with **hepatomegaly** and **fasting hypoglycemia**. - While it can involve skeletal muscle, the **ischemic forearm test** would usually show a **blunted but present lactate rise**, unlike the flat response seen here. *Branching enzyme deficiency* - Known as **Andersen disease** (GSD Type IV), it typically presents in infancy with **liver cirrhosis**, **failure to thrive**, and **hypotonia**. - It results in the accumulation of **abnormal glycogen (amylopectin-like)** with fewer branch points, which is fatal at a young age and does not match the exercise-induced presentation. *Phosphorylase kinase deficiency* - This is most commonly an **X-linked** condition (GSD Type IX) that primarily affects the **liver**, leading to hepatomegaly and growth retardation. - While muscle isoforms exist, the clinical picture is usually milder than McArdle disease and does not characteristically feature the **'second wind' phenomenon** or severe myoglobinuria.

Metabolism US Medical PG Question 3: Researchers are experimenting with hormone levels in mice in fasting and fed states. To test hormone levels in the fed state, the mice are given an oral glucose load and various hormones are measured in a blood sample. Researchers are most interested in the hormone whose blood levels track evenly with C-peptide levels. The hormone the researchers are most interested in is responsible for which of the following actions in the body?

• A. Protein catabolism
• B. Fatty acid breakdown
• C. Fatty acid synthesis (Correct Answer)
• D. Ketogenesis
• E. Lipolysis

Metabolism Explanation: ***Fatty acid synthesis*** - The hormone whose blood levels track evenly with **C-peptide** levels after a glucose load is **insulin**. - Insulin is a key anabolic hormone that promotes **fatty acid synthesis** from excess glucose in the fed state, particularly in the liver and adipose tissue. *Protein catabolism* - **Insulin** is an anabolic hormone that generally **inhibits protein catabolism** and promotes protein synthesis. - Conditions like **glucagon excess** or **cortisol excess** promote protein catabolism, not insulin. *Fatty acid breakdown* - **Insulin inhibits fatty acid breakdown** (beta-oxidation) by suppressing hormone-sensitive lipase. - **Glucagon** and **epinephrine** promote fatty acid breakdown, especially during fasting. *Ketogenesis* - **Insulin inhibits ketogenesis** by reducing the supply of fatty acids to the liver and inhibiting the enzymes involved in ketone body formation. - **Glucagon** and **low insulin levels** (as in uncontrolled diabetes or prolonged fasting) promote ketogenesis. *Lipolysis* - **Insulin is a potent inhibitor of lipolysis** (breakdown of triglycerides into fatty acids and glycerol) in adipose tissue. - **Glucagon**, **catecholamines**, and **growth hormone** stimulate lipolysis.

Metabolism US Medical PG Question 4: The balance between glycolysis and gluconeogenesis is regulated at several steps, and accumulation of one or more products/chemicals can either promote or inhibit one or more enzymes in either pathway. Which of the following molecules if increased in concentration can promote gluconeogenesis?

• A. ADP
• B. Acetyl-CoA (Correct Answer)
• C. AMP
• D. Fructose-2,6-bisphosphate
• E. Insulin

Metabolism Explanation: ***Acetyl-CoA*** - **Acetyl-CoA** promotes gluconeogenesis by activating **pyruvate carboxylase**, the enzyme that converts pyruvate to oxaloacetate, effectively pushing the pathway forward. - High levels of **Acetyl-CoA** generally signal a state of abundant energy from fatty acid oxidation, indicating that glucose is not immediately needed for energy and can be synthesized for storage or use elsewhere. *ADP* - **ADP** is a key indicator of low cellular energy and **stimulates** glycolysis while **inhibiting** gluconeogenesis to produce ATP. - Its presence signals a need for energy synthesis rather than glucose production. *AMP* - **AMP** also signals low energy status and is a powerful **allosteric activator** of **phosphofructokinase-1 (PFK-1)**, the rate-limiting enzyme in glycolysis. - Activates **AMP-activated protein kinase (AMPK)**, which promotes catabolic processes like glycolysis and inhibits anabolic processes like gluconeogenesis. *Fructose-2,6-bisphosphate* - **Fructose-2,6-bisphosphate** is a potent **allosteric activator** of **PFK-1** in glycolysis and a strong **inhibitor** of **fructose-1,6-bisphosphatase** in gluconeogenesis. - Its levels increase in response to insulin, promoting glucose utilization and inhibiting glucose production. *Insulin* - **Insulin** is a hormone that **promotes glucose uptake** and utilization by tissues and **inhibits gluconeogenesis**. - It achieves this by activating enzymes involved in glycolysis and glycogen synthesis while inhibiting key enzymes in gluconeogenesis, such as **fructose-1,6-bisphosphatase**.

Metabolism US Medical PG Question 5: You have been asked to deliver a lecture to medical students about the effects of various body hormones and neurotransmitters on the metabolism of glucose. Which of the following statements best describes the effects of sympathetic stimulation on glucose metabolism?

• A. Norepinephrine causes increased glucose absorption within the intestines.
• B. Without epinephrine, insulin cannot act on the liver.
• C. Peripheral tissues require epinephrine to take up glucose.
• D. Epinephrine increases liver glycogenolysis. (Correct Answer)
• E. Sympathetic stimulation to alpha receptors of the pancreas increases insulin release.

Metabolism Explanation: ***Epinephrine increases liver glycogenolysis.*** - **Epinephrine**, released during sympathetic stimulation, primarily acts to increase **glucose availability** for immediate energy. - It achieves this by stimulating **glycogenolysis** (breakdown of glycogen into glucose) in the liver via **beta-adrenergic receptors**. *Norepinephrine causes increased glucose absorption within the intestines.* - **Norepinephrine** primarily causes **vasoconstriction** and can *decrease* **intestinal motility** and nutrient absorption due to shunting blood away from the digestive tract during stress. - Glucose absorption is mainly regulated by digestive enzymes and transport proteins, not directly increased by norepinephrine. *Without epinephrine, insulin cannot act on the liver.* - **Insulin** acts on the liver independent of epinephrine to promote **glucose uptake**, **glycogenesis**, and **lipid synthesis**. - Epinephrine and insulin have **antagonistic effects** on liver glucose metabolism; epinephrine increases glucose output, while insulin decreases it. *Peripheral tissues require epinephrine to take up glucose.* - **Insulin** is the primary hormone required for **glucose uptake** by most peripheral tissues, especially **muscle** and **adipose tissue**, via **GLUT4 transporters**. - Epinephrine generally *reduces* glucose uptake by peripheral tissues to preserve glucose for the brain during stress. *Sympathetic stimulation to alpha receptors of the pancreas increases insulin release.* - Sympathetic stimulation, primarily acting through **alpha-2 adrenergic receptors** on pancreatic beta cells, actually **inhibits** **insulin secretion**. - This inhibition helps to increase blood glucose levels by reducing insulin's glucose-lowering effects.

Metabolism Flashcard 1 of 5

Question: During oxidative phosphorylation, how many ATP are produced per FADH2?

Answer: 2

Metabolism Flashcard 2 of 5

Question: Where does oxidative phosphorylation take place?

Answer: mitochondria

Metabolism Flashcard 3 of 5

Question: Where does the TCA cycle take place?

Answer: mitochondria

Metabolism Flashcard 4 of 5

Question: Where does acetyl-CoA production take place?

Answer: mitochondria

Metabolism Flashcard 5 of 5

Question: Where does heme synthesis occur?

Answer: steps in both the cytoplasm and mitochondria