Metabolism

Metabolism US Medical PG Question 1: Which of the following foods should be consumed to prevent thiamine deficiency?

• A. Whole grain cereals and legumes (Correct Answer)
• B. Dairy products and eggs
• C. Fresh fruits and vegetables
• D. Polished white rice
• E. Red meat and poultry

Metabolism Explanation: ***Whole grain cereals and legumes*** - **Whole grain cereals** (brown rice, oats, wheat germ, fortified cereals) and **legumes** (beans, lentils, peas) are **excellent natural sources of thiamine (vitamin B1)** - They retain the **bran and germ** layers where thiamine is concentrated - Regular consumption effectively prevents **thiamine deficiency** and associated conditions like beriberi and Wernicke-Korsakoff syndrome - This is the **primary dietary recommendation** for thiamine adequacy *Polished white rice* - Polished white rice has the **bran and germ removed** during processing, eliminating most of the thiamine content - Consuming polished white rice as a staple **causes thiamine deficiency**, leading to **beriberi** (common in populations with rice-based diets) - Unless fortified with thiamine, polished white rice contributes to deficiency rather than preventing it *Dairy products and eggs* - While nutritious, dairy products and eggs contain **relatively low amounts of thiamine** - Not reliable sources for meeting daily thiamine requirements - Contribute to overall nutrition but insufficient alone to prevent thiamine deficiency *Fresh fruits and vegetables* - Most fruits and vegetables contain **modest amounts of thiamine** compared to whole grains - Some exceptions include peas, asparagus, and Brussels sprouts, but typical servings provide limited thiamine - Important for overall health but not primary thiamine sources *Red meat and poultry* - Pork is actually a **good source of thiamine**, particularly organ meats - However, **whole grains and legumes** remain the most reliable and accessible plant-based sources - Red meat and poultry provide moderate thiamine but are not the best answer for preventing deficiency in general populations

Metabolism US Medical PG Question 2: A patient with homocystinuria presents with ectopia lentis (dislocation of the lens). Which vitamin should be supplemented?

• A. Vitamin B12
• B. Vitamin B6 (Correct Answer)
• C. Thiamine
• D. Vitamin B9 (Folate)
• E. Vitamin C

Metabolism Explanation: ***Vitamin B6*** - Many cases of **homocystinuria** are due to a deficiency in **cystathionine beta-synthase (CBS)**, an enzyme that requires **pyridoxal phosphate (active B6)** as a cofactor. - Supplementing with **high doses of vitamin B6** can significantly improve outcomes in patients with **B6-responsive homocystinuria** by increasing residual CBS enzyme activity. *Vitamin B12* - While vitamin B12 (cobalamin) is a cofactor for **methionine synthase**, an enzyme involved in homocysteine metabolism, it is not the primary treatment for **homocystinuria due to CBS deficiency**. - B12 deficiency can lead to increased homocysteine levels, but B12 supplementation alone will not address the underlying enzyme defect in most cases of homocystinuria. *Thiamine* - **Thiamine (Vitamin B1)** is essential for carbohydrate metabolism and nerve function, but it has no direct role in the metabolic pathway involved in homocystinuria. - Thiamine deficiency causes **beriberi** and **Wernicke-Korsakoff syndrome**, symptoms distinctly different from homocystinuria. *Vitamin B9 (Folate)* - **Folate** is a cofactor for **methionine synthase**, working alongside vitamin B12 to convert homocysteine back to methionine. - While folate deficiency can contribute to hyperhomocysteinemia, it is not the primary therapeutic intervention for homocystinuria caused by **CBS deficiency**. *Vitamin C* - **Vitamin C (ascorbic acid)** is important for collagen synthesis and acts as an antioxidant, but it has no role in homocysteine metabolism or the treatment of homocystinuria. - Vitamin C deficiency causes **scurvy**, which presents with bleeding gums, petechiae, and poor wound healing—completely unrelated to homocystinuria.

Metabolism US Medical PG Question 3: What is the primary function of IL-8?

• A. Chemotaxis (Correct Answer)
• B. Lymphocyte proliferation
• C. TH1 activation
• D. Fever
• E. B cell activation

Metabolism Explanation: ***Chemotaxis*** - **IL-8** (also known as **CXCL8**) is a potent **chemokine** that primarily functions to recruit and activate **neutrophils** to sites of inflammation. - It guides these immune cells by forming a chemical gradient, allowing them to extravasate from blood vessels and migrate to the infected or injured tissue. *Lymphocyte proliferation* - Lymphocyte proliferation is primarily stimulated by **IL-2**, which acts as a growth factor for T cells. - While IL-8 contributes to the inflammatory environment, its direct role in inducing lymphocyte cell division is minor compared to its chemotactic function. *TH1 activation* - **TH1 cell activation** is mainly driven by **IL-12** and **IFN-γ**, which promote the differentiation and function of T helper 1 cells, crucial for fighting intracellular pathogens. - IL-8's role is unrelated to guiding TH1 cell differentiation. *Fever* - Fever is primarily induced by **pyrogenic cytokines** such as **IL-1**, **IL-6**, and **TNF-α**, which act on the hypothalamus to raise body temperature. - While IL-8 is part of the inflammatory response that can sometimes coincide with fever, it does not directly act as a pyrogen. *B cell activation* - **B cell activation** and differentiation are primarily regulated by interleukins such as **IL-4**, **IL-5**, **IL-6**, and **IL-21**, which promote antibody production and class switching. - IL-8 does not play a significant role in B cell function; its action is focused on innate immunity, particularly neutrophil recruitment.

Metabolism US Medical PG Question 4: A 45-year-old patient presents with joint pain and weakness and is known to have homocystinuria. Which vitamin is required in the treatment?

• A. Vitamin B6 (Correct Answer)
• B. Vitamin B12
• C. Vitamin B7
• D. Vitamin B1
• E. Vitamin B9

Metabolism Explanation: ***Vitamin B6*** - **Homocystinuria** is often caused by a deficiency in the enzyme **cystathionine beta-synthase**, which requires **pyridoxal phosphate (active form of B6)** as a cofactor. - Supplementation with high-dose **vitamin B6** can help some patients by increasing the residual activity of the enzyme, thereby reducing **homocysteine levels**. - This is the **primary treatment** for **B6-responsive homocystinuria** (approximately 50% of cases respond to B6 therapy). *Vitamin B12* - Vitamin B12 is a cofactor for the enzyme **methionine synthase**, which converts homocysteine back to methionine. - While it plays a role in homocysteine metabolism, **vitamin B6** is typically the primary treatment for homocystinuria caused by **cystathionine beta-synthase deficiency**. *Vitamin B9* - Vitamin B9 (folic acid) works together with **vitamin B12** as a cofactor in the **remethylation pathway** via methionine synthase. - While folate supplementation may help lower homocysteine levels, it is **not the primary treatment** for classical homocystinuria due to cystathionine beta-synthase deficiency. - **Vitamin B6** remains the first-line vitamin therapy for enzyme deficiency-related homocystinuria. *Vitamin B7* - Vitamin B7, or **biotin**, is a cofactor for carboxylase enzymes and is involved in fatty acid synthesis and gluconeogenesis. - It has no direct role in the metabolism of **homocysteine** or the treatment of homocystinuria. *Vitamin B1* - Vitamin B1, or **thiamine**, is essential for carbohydrate metabolism and nerve function. - It is not involved in the metabolic pathways that regulate **homocysteine levels** or the treatment of homocystinuria.

Metabolism US Medical PG Question 5: A neonate was brought to the hospital with chief complaints of poor feeding, vomiting, acidosis, and cataract. Benedict's test on urine was positive, but urinary glucose was negative. What is the defective enzyme in the above-mentioned disorder?

• A. Galactose 1-phosphate uridyl transferase (Correct Answer)
• B. Fructokinase
• C. Lactase
• D. Sucrase
• E. Aldolase B

Metabolism Explanation: ***Galactose 1-phosphate uridyl transferase*** - This enzyme deficiency leads to **classic galactosemia**, characterized by the accumulation of **galactose-1-phosphate**, which is toxic. - Clinical features like **poor feeding, vomiting, acidosis, and cataracts** are typical, and a positive **Benedict's test** (detecting reducing sugars like galactose) with negative urinary glucose confirms the presence of another reducing sugar. *Fructokinase* - Deficiency of fructokinase causes **essential fructosuria**, a benign condition where **fructose** accumulates in the urine. - Unlike classic galactosemia, it does not present with severe symptoms like **acidosis** or **cataracts**. *Aldolase B* - **Aldolase B deficiency** causes hereditary fructose intolerance, presenting with **vomiting, hypoglycemia, and hepatomegaly** after fructose ingestion. - It does not cause **cataracts**, and Benedict's test would detect fructose, but the clinical context (symptoms with fructose/sucrose intake) differs from galactosemia. *Lactase* - **Lactase deficiency** (lactose intolerance) results in gastrointestinal symptoms such as **bloating, diarrhea, and abdominal pain** upon lactose consumption. - It does not typically cause **acidosis, cataracts**, or a positive Benedict's test in urine unless secondary bacterial fermentation leads to other reducing substances. *Sucrase* - **Sucrase-isomaltase deficiency** leads to the malabsorption of sucrose, causing symptoms similar to lactose intolerance like **diarrhea and abdominal cramping**. - It does not result in the systemic, severe metabolic derangements or signs like **cataracts** seen in classic galactosemia.

Metabolism US Medical PG Question 6: A patient's relatives sent a message on social media to the consulting doctor, mentioning that the patient's urinary coproporphyrin test is positive. What is the probable cause?

• A. Lead poisoning (Correct Answer)
• B. Asbestosis
• C. Silicosis
• D. Mercury poisoning
• E. Arsenic poisoning

Metabolism Explanation: ***Lead poisoning*** - **Lead poisoning** is associated with an increase in **urinary coproporphyrin III**, as lead inhibits the enzyme **coproporphyrinogen oxidase** in the heme synthesis pathway. - This leads to the accumulation and excretion of **coproporphyrin III** in the urine, making it a valuable biomarker for lead exposure. *Asbestosis* - **Asbestosis** is a chronic lung disease caused by inhaling **asbestos fibers**, leading to diffuse interstitial fibrosis. - It does not directly affect the **heme synthesis pathway** or cause an increase in urinary coproporphyrins. *Silicosis* - **Silicosis** is a chronic occupational lung disease caused by inhaling **crystalline silica dust**, resulting in pulmonary fibrosis. - It is not associated with alterations in **porphyrin metabolism** or increased urinary coproporphyrin levels. *Mercury poisoning* - While **mercury poisoning** can affect various organ systems, including renal and neurological, it is not primarily associated with disturbances in the **heme synthesis pathway** or elevated urinary coproporphyrins. - **Mercury poisoning** often manifests with symptoms like **tremors**, **neurological deficits**, and **kidney damage**. *Arsenic poisoning* - **Arsenic poisoning** causes a variety of systemic effects including gastrointestinal symptoms, peripheral neuropathy, and skin changes (hyperpigmentation, hyperkeratosis). - Unlike lead poisoning, **arsenic does not significantly elevate urinary coproporphyrin III** levels, making it distinguishable from lead toxicity through this biomarker.

Metabolism US Medical PG Question 7: A 5-year-old girl was washing her doll with shampoo containing rotenone. Her mother noticed her in an unconscious state. Which enzyme is inhibited by the above chemical?

• A. NADH dehydrogenase (Correct Answer)
• B. Succinate dehydrogenase
• C. Cytochrome C
• D. Cytochrome oxidase
• E. Cytochrome b-c1 complex

Metabolism Explanation: ***NADH dehydrogenase*** - **Rotenone** is a potent **inhibitor of mitochondrial complex I (NADH dehydrogenase)**, preventing the transfer of electrons from NADH to ubiquinone. - This inhibition disrupts the **electron transport chain**, leading to a halt in ATP synthesis and cellular energy failure, causing symptoms like unconsciousness. *Succinate dehydrogenase* - **Succinate dehydrogenase** (Complex II) is involved in both the **Krebs cycle and electron transport chain**, but is not directly inhibited by rotenone. - Only severe compromise of the electron transport chain can cause a secondary effect, but not direct enzyme inhibition. *Cytochrome C* - **Cytochrome C** is a mobile electron carrier in the electron transport chain, but it is not directly inhibited by rotenone. - **Cytochrome C** transfers electrons from complex III to complex IV. *Cytochrome oxidase* - **Cytochrome oxidase** (Complex IV) is responsible for the final transfer of electrons to oxygen, which is not inhibited by rotenone. - Inhibitors like **cyanide and carbon monoxide** specifically target **cytochrome oxidase**. *Cytochrome b-c1 complex* - **Cytochrome b-c1 complex** (Complex III) catalyzes electron transfer from ubiquinol to cytochrome C, but is not inhibited by rotenone. - This complex is specifically inhibited by **antimycin A**, not rotenone.

Metabolism US Medical PG Question 8: A patient presents with symptoms of dermatitis, dementia, and cognitive decline. Which micronutrient deficiency is most likely responsible?

• A. Niacin (Correct Answer)
• B. Thiamine
• C. Tryptophan
• D. Retinol
• E. Riboflavin

Metabolism Explanation: ***Niacin*** - The classic triad of symptoms known as the "3 Ds"—**dermatitis, dementia, and diarrhea**—is characteristic of **pellagra**, a severe deficiency of **niacin (vitamin B3)**. - **Cognitive decline** is a common manifestation of the neurological symptoms associated with dementia in pellagra. *Thiamine* - **Thiamine (vitamin B1)** deficiency causes **beriberi**, leading to cardiovascular (wet beriberi) or neurological (dry beriberi/Wernicke-Korsakoff syndrome) symptoms. - While **fatigue and cognitive impairment** can occur, the constellation of prominent dermatitis and severe dementia is not typical of primary thiamine deficiency. *Tryptophan* - **Tryptophan** is an **essential amino acid** and a precursor to niacin. A deficiency in tryptophan could indirectly lead to niacin deficiency. - However, the direct deficiency of tryptophan as the primary cause of the "3 Ds" is less common than a direct niacin deficiency or impaired niacin synthesis. *Retinol* - **Retinol (vitamin A)** deficiency primarily affects **vision**, leading to **night blindness** and xerophthalmia. - It also plays a role in immune function and epithelial cell integrity, but it does not cause the specific triad of dermatitis, dementia, and cognitive decline seen here. *Riboflavin* - **Riboflavin (vitamin B2)** deficiency causes **angular stomatitis, cheilosis, and glossitis** along with seborrheic dermatitis. - While it can cause skin manifestations, it does not typically present with the severe dementia and cognitive decline characteristic of pellagra.

Metabolism US Medical PG Question 9: A mother brings her 14 -year-old mentally retarded son to the OPD, who is suffering from joint pain and has an irresistible urge to bite his fingers and lips. His serum uric acid level was found to be elevated. What is the disorder?

• A. Lesch-Nyhan syndrome (Correct Answer)
• B. Xanthine oxidase deficiency
• C. CPS II defect
• D. Thymidylate synthetase
• E. Von Gierke disease

Metabolism Explanation: ***Lesch-Nyhan syndrome*** - This syndrome is characterized by **X-linked recessive inheritance** and a deficiency of the enzyme **hypoxanthine-guanine phosphoribosyltransferase (HGPRT)**, leading to an overproduction of uric acid. - Clinical manifestations include **hyperuricemia**, **gout-like arthritis**, **neurological dysfunction** (mental retardation, dystonia), and a distinctive feature of **self-mutilating behaviors** such as biting fingers and lips. *Xanthine oxidase deficiency* - This condition leads to an accumulation of **hypoxanthine** and **xanthine** due to impaired conversion to uric acid. - While it can cause kidney stones and some joint pain, it typically results in *low* serum uric acid levels and does not present with the characteristic self-mutilating behavior or severe neurological deficits seen in Lesch-Nyhan. *CPS II defect* - **Carbamoyl phosphate synthetase II (CPS II)** is involved in *pyrimidine synthesis*, not purine metabolism. - A defect in CPS II would lead to issues with pyrimidine production and typically presents with megaloblastic anemia or other symptoms related to pyrimidine deficiency, not hyperuricemia or self-mutilation. *Thymidylate synthetase* - **Thymidylate synthetase (TS)** is an enzyme critical for the synthesis of **thymidylate**, a precursor for DNA synthesis. - Inhibition or deficiency of TS is primarily associated with DNA replication issues, megaloblastic anemia, and is a target for chemotherapy, not with hyperuricemia or the neurological and behavioral symptoms described. *Von Gierke disease* - **Von Gierke disease** (Glycogen storage disease type Ia) is caused by deficiency of **glucose-6-phosphatase**, leading to impaired conversion of glucose-6-phosphate to glucose. - While it can cause **hyperuricemia** due to increased uric acid production from accelerated purine degradation, the clinical presentation is distinct with **hepatomegaly**, **hypoglycemia**, **lactic acidosis**, and growth retardation. - It does **not** present with self-mutilating behavior or the severe neurological dysfunction characteristic of Lesch-Nyhan syndrome.

Metabolism US Medical PG Question 10: An infant presents with vomiting after feeding. Benedict's test was positive for a non-glucose reducing substance. What is the most likely diagnosis?

• A. Galactosemia due to GAL-1-P Uridyl Transferase enzyme deficiency (Correct Answer)
• B. Fructosuria due to Fructokinase deficiency
• C. Hereditary fructose intolerance due to Aldolase B deficiency
• D. Primary lactose intolerance
• E. Glycogen storage disease due to Glucose-6-phosphatase deficiency

Metabolism Explanation: ***Galactosemia due to GAL-1-P Uridyl Transferase enzyme deficiency*** - Vomiting after feeding in an infant, coupled with a **positive Benedict's test** for a **non-glucose reducing substance**, is highly indicative of galactosemia. The accumulation of **galactose-1-phosphate** and **galactitol** leads to toxicity and symptoms. - This enzyme deficiency, causing **classic galactosemia**, prevents the proper metabolism of **galactose**, leading to its buildup. *Fructosuria due to Fructokinase deficiency* - This condition is a **benign metabolic disorder** with no significant clinical symptoms. - While it would lead to fructose in the urine, the infant would not typically present with **vomiting after feeding**. *Hereditary fructose intolerance due to Aldolase B deficiency* - Symptoms usually appear after the introduction of **fructose-containing foods** into the diet, causing severe hypoglycemia and vomiting. - The positive Benedict's test in this scenario would typically indicate a reducing substance in the urine, while fructose intolerance is characterized by **hypoglycemia** and metabolic crises upon fructose ingestion. *Glycogen storage disease due to Glucose-6-phosphatase deficiency* - This disorder primarily causes **hypoglycemia** and liver enlargement, not primarily vomiting after feeding due to a **non-glucose reducing substance**. - Glucose-6-phosphatase deficiency (Von Gierke's disease) leads to an inability to release **glucose from glycogen** and causes severe hypoglycemia, often requiring frequent feeding. *Primary lactose intolerance* - While lactose intolerance can cause vomiting and gastrointestinal symptoms, it is **extremely rare in infants** (primary lactose intolerance is a late-onset condition). - Lactose would be a reducing sugar, but the key differentiator is that **galactose** (from galactosemia) is the non-glucose reducing substance detected in this case, along with the typical **toxic presentation** in neonates.

Metabolism Flashcard 1 of 10

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

Answer: 2

Metabolism Flashcard 2 of 10

Question: Where does oxidative phosphorylation take place?

Answer: mitochondria

Metabolism Flashcard 3 of 10

Question: Where does the TCA cycle take place?

Answer: mitochondria

Metabolism Flashcard 4 of 10

Question: Where does acetyl-CoA production take place?

Answer: mitochondria

Metabolism Flashcard 5 of 10

Question: Where does heme synthesis occur?

Answer: steps in both the cytoplasm and mitochondria

Metabolism Flashcard 6 of 10

Question: Where does gluconeogenesis occur?

Answer: steps in both the cytoplasm and mitochondria

Metabolism Flashcard 7 of 10

Question: Where does the HMP shunt take place?

Answer: cytoplasm

Metabolism Flashcard 8 of 10

Question: aldose reductase

Answer:

Extra Information: sequester glucose in cell or transform it into fructoseglucosesorbitol

Metabolism Flashcard 9 of 10

Question: sorbitol dehydrogenase

Answer:

Extra Information: sorbitolfructosenotably LOW in Schwann cells, retinal cells, kidney cells

Metabolism Flashcard 10 of 10

Question: TCA cycle

Answer: isocitrate dehydrogenase