Metabolism — Flashcards

Flashcard 801: 22 y/o man comes with recurrent blistering on the back of his hands and forarms for the past several years. -He has used overcounter meds, but symptoms didn't improve. -He has no exposure to chemicals or animals -Physical exam: vesicles and erosions on the dorsum of both hands. -Which enzymes is most likely deficient in this patient in relation to heme synthesis pathway?

Answer: Uroporphyrinogen decarboxylase because patient present with skin blistering (photosensitivity) due to Porphyria cutanea tarda (PCT)

Flashcard 802: 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 803: What do these two end-products have in common? - Sorbitol - Galactitol

Answer: They both can cause cataracts and are synthesized by the same enzyme: Aldose reductase.

Flashcard 804: 24 y/o man comes with episodic anemia, jaundice, & dark urine. - These episodes typically occur after use of certain drugs or following infection. - History: brother has similar episodes. - Peripheral blood smear: shows bite cells and Heinz bodies. Deficiency of what enzyme would most likely result in a condition similar to this patient's presentation?

Answer: Glutathione reductase

Extra: The clinical vignette describes **Glucose-6-phosphate dehydrogenase (G6PD) deficiency** (episodic hemolysis triggered by oxidative stress). **Glutathione reductase** deficiency results in a similar presentation because it is the enzyme responsible for regenerating reduced glutathione (GSH) using NADPH. Without GSH, RBCs cannot neutralize reactive oxygen species, leading to Heinz body formation and bite cells.

Flashcard 805: 78 y/o woman presents with tenderness and easy bleeding of the gums when brushing her teeth. - Physical exam: swollen gingiva that bleed on probing. - Skin: perifollicular hemorrhages and petechiae are noted. Her symptoms are most likely caused by hypoactivity of an enzyme found in which cellular compartment?

Answer: Rough endoplasmic reticulum (RER) This is where Vitamin C-dependent hydroxylation of proline and lysine residues (on procollagen chains) occurs. Deficiency leads to scurvy.

Flashcard 806: 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 807: 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 808: Identify the required vitamin cofactors for the following metabolic reactions: - Glucose to ribose-5-phosphate - Pyruvate to acetyl-CoA - Pyruvate to alanine - Pyruvate to oxaloacetate - Succinate to oxaloacetate

Answer: - Glucose to ribose-5-phosphate: Niacin (B3) for NADPH production. - Pyruvate to acetyl-CoA: Thiamine (B1), Riboflavin (B2), Niacin (B3), Pantothenic acid (B5), and Lipoic acid (Cofactors for Pyruvate Dehydrogenase). - Pyruvate to alanine: Vitamin B6 (Pyridoxine) for ALT (transamination). - Pyruvate to oxaloacetate: Biotin (B7) for Pyruvate Carboxylase. - Succinate to oxaloacetate: Riboflavin (B2) for Succinate Dehydrogenase (FAD) and Niacin (B3) for Malate Dehydrogenase (NAD+).

Flashcard 809: 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.

Flashcard 810: What are the disacharide breakdown of: -Sucrose -Lactose -Maltose

Answer: Sucrose: Glucose + fructose -Lactose: Glucose + galactose -Maltose: Glucose + Glucose