Metabolism — Flashcards

Flashcard 791: What are the followings are associated with? -Heme oxygenase -Biliverdin reductase

Answer: Heme oxygenase: convert heme to biliverdin (green color) -Biliverdin reductase: convert biliverdin to bilirubin (yellow color)

Flashcard 792: 76 y/o man comes with excessive fatigue and altered mental status. - The patient has long history of diabetes mellitus. - Physical Exam: Dry mouth, cracked lips, severe cataract formation. - Lab test: Glucose 750 mg/dL & normal ketone level. - Pathophysiology of his cataract formation involves certain enzymes within the lens. - An enzyme called aldose reductase produces sorbitol, a substance that cannot readily exit the lens cells. - What is the most likely end product of sorbitol metabolism in the lens of healthy individuals?

Answer: Fructose **Polyol Pathway:** Glucose → (Aldose reductase) → Sorbitol → (Sorbitol dehydrogenase) → Fructose. In hyperglycemia, sorbitol is produced faster than it can be metabolized to fructose. Sorbitol accumulates, causing osmotic damage. **Tissue distribution of Sorbitol dehydrogenase:** * **Low/Absent:** Lens, Retina, Schwann cells, Kidneys (prone to damage). * **High:** Liver, Ovaries, Seminal vesicles (efficiently convert sorbitol to fructose).

Flashcard 793: Xylulose-5-phosphate is an intermediate in which metabolic pathway?

Answer: Pentose phosphate pathway (HMP shunt)

Flashcard 794: 74 y/o woman comes with 2 days of left leg pain and numbness. - History of A. Fib & hypertension. - Left lower limb is pale & cold to palpation below the knee. - Ultrasound: occluding thrombus & a left femoral embolectomy is performed. - Post procedure dorsalis pedis & posterior tibial pulses become palpable. - Several hours later, patient feels severe left calf pain, with absent distal pulses. - Physician suspects: injury of the reperfused muscles due to overproduction of reactive oxygen species. - Which enzymes are most likely to help neutralize these toxic molecules?

Answer: Superoxide dismutase, Catalase, and Glutathione peroxidase This patient is presenting with **acute compartment syndrome** secondary to **reperfusion injury**. Reperfusion leads to the overproduction of reactive oxygen species (ROS). These molecules are neutralized by antioxidant enzymes: - **Superoxide dismutase** (converts superoxide to hydrogen peroxide) - **Catalase** and **Glutathione peroxidase** (convert hydrogen peroxide to water)

Flashcard 795: Describe the role of the following molecules in handling oxygen species and toxins: - Cytochrome oxidase - Cytochrome P450 - Myeloperoxidase - NADPH - Superoxide dismutase

Answer: • Cytochrome oxidase: Final component of the electron transport chain (Complex IV); reduces O2 to H2O, preventing the formation of reactive oxygen species (ROS). • Cytochrome P450: Involved in Phase I metabolism (hydroxylation) of endogenous compounds and exogenous drugs/toxins. • Myeloperoxidase: Found in neutrophil granules; converts H2O2 to HOCl (hypochlorous acid/bleach) during the respiratory burst to destroy pathogens. • NADPH: Provides reducing equivalents for both the generation of ROS (via NADPH oxidase) and the neutralization of ROS (via Glutathione reductase). • Superoxide dismutase: Neutralizes superoxide (O2•-) radicals by converting them into oxygen and hydrogen peroxide (H2O2).

Extra: NADPH is a critical cofactor. In the respiratory burst, it is used by NADPH oxidase to create superoxide. In cellular antioxidant defense, it is used by glutathione reductase to regenerate reduced glutathione, which then neutralizes H2O2. Chronic Granulomatous Disease (CGD) involves a deficiency in NADPH oxidase, leading to recurrent infections with catalase-positive organisms.

Flashcard 796: A 5 month old boy comes with poor feeding. -Physical exam: hepatomegaly and hypotonia in all 4 limbs. -Cardiac auscultation: gallop rhythm -Chest Xray: Severe cardiomegaly -Muscle biopsy: Enlarged lysosomes containing periodic acid-schiff (PAS)-positive material. -Which enzymes is most likely deficient in this patient?

Answer: Acid alpha-glucosidase (alpha 1,4 glucosidase deficiency) or Acid maltase deficiency due to Pompe disease (Very Poor Carbs Metabolism) Accumulation of glycogen in lysosomal vesicles. Present with: Normal glucose levels, severe cardiomegaly.

Flashcard 797: 22 y/o comes with 5 day history of Nausea, constipation, and severe, poorly localized abdominal pain. -She also reports anxiety, poor sleep quality and tingling of limbs. -She doesn't take any drugs,no smoking, medication or use alcohol. -Patient receives intravenous infusion of heme preparation that leads to rapid resolution of her symptoms. -The improvement in symptoms is most likely due to treatment-induced downregulation of what enzymes?

Answer: Aminolevulinate synthase (ALA Synthase) which is the rate limiting step in heme synthesis. Patient has Acute intermittent porphyria (recurrent abdominal pain, neuropsychosis symptoms) Symptoms: 5 P's: Port wine urine, polyneuropathy, painful abdomen, psychosis, precipitated by drugs (cytochrome p450) Glucose or heme makes better. (inhibits ALA synthase)

Flashcard 798: The followings compounds will serve as a precursor to what? -Arginine -Carotene -Cholesterol -Orotic acid -Phenylalanine -Tryptophan

Answer: Arginine: precursor to urea, nitric oxide, ornithine, agmatine, creatine. -Carotene: Precursor to vit. A. -Cholesterol: precursor to steroid hormones. -Orotic acid: Precursor to pyrimidine to synthesize DNA. -Phenylalanine: Precursor to tyrosine to create catecholamines. -Tryptophan: Precursor to Niacin (B3)

Flashcard 799: What is the status/relevance of the following enzymes in **Lesch-Nyhan syndrome**? - Aspartate carbamoyltransferase - Dihydroorotase - Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) - PRPP amidotransferase (Phosphoribosyl pyrophosphate amidotransferase) - Ribonucleotide reductase - Thymidylate synthase

Answer: - **HGPRT**: **Deficient/Absent** (this is the primary genetic defect). - **PRPP amidotransferase**: **Activity increases** (due to elevated PRPP levels and decreased feedback inhibition, resulting in increased *de novo* purine synthesis). - **Aspartate carbamoyltransferase, Dihydroorotase, and Thymidylate synthase**: **Unaffected** (these are enzymes of pyrimidine synthesis). - **Ribonucleotide reductase**: **Unaffected** (converts ribonucleotides to deoxyribonucleotides for both purines and pyrimidines).

Extra: Lesch-Nyhan syndrome is an X-linked recessive disorder characterized by HGPRT deficiency. This leads to: 1. Failure of the purine salvage pathway (Hypoxanthine/Guanine -> IMP/GMP). 2. Accumulation of PRPP (which is not consumed by the salvage pathway). 3. Increased *de novo* purine synthesis (because PRPP is a potent activator of PRPP amidotransferase, the rate-limiting enzyme of the de novo pathway). 4. Excess uric acid production (hyperuricemia) and characteristic behavioral symptoms like self-mutilation.

Flashcard 800: With which signaling pathways are the following events associated (in the context of growth factors and cellular regulation)? - **Ca²⁺ efflux from the endoplasmic reticulum** - **cAMP accumulation** - **Dimerization of STAT proteins** - **Activation of S6 kinase (protein synthesis)** - **Translocation of ERK (MAPK) to the nucleus** (Choices: MAP-kinase pathway, mTOR pathway, Inositol phospholipid pathway, cAMP pathway, JAK/STAT pathway)

Answer: 1. **Inositol phospholipid pathway**: Phospholipase C (PLC) → IP₃ → Ca²⁺ release from the endoplasmic reticulum. 2. **cAMP pathway**: Gs-protein → Adenylate cyclase → ↑cAMP → Protein Kinase A (PKA). 3. **JAK/STAT pathway**: Ligand binding → JAK (non-receptor tyrosine kinase) phosphorylation → STAT dimerization. 4. **mTOR pathway**: Activated downstream of PI3K/Akt; regulates protein synthesis (translation) via **S6 kinase (S6K)** and 4E-BP1. 5. **MAP-kinase pathway**: Growth factor → Ras → Raf → MEK → ERK (MAPK); activated ERK translocates to the nucleus to initiate gene transcription (STAT proteins also translocate to the nucleus).

Extra: **JAK/STAT Pathway Ligands (Mnemonic: PIGGLET):** - **P**: Prolactin - **I**: Immunomodulators (Cytokines: IL-2, IL-6, IFN) - **G**: Growth Hormone (GH) - **G**: G-CSF - **L**: Leptin - **E**: Erythropoietin (EPO) - **T**: Thrombopoietin (TPO) **Note on cGMP:** - **Visual phototransduction**: Light → Transducin → PDE activation → **↓cGMP** (occurs in the retina; classic example of rapid cGMP decrease). - **ANP, BNP, and NO**: Activate Guanylate Cyclase → **↑cGMP** → Vasodilation. - **PDE-5 inhibitors** (e.g., Sildenafil) prevent cGMP breakdown.