Metabolism — Flashcards

Flashcard 861: What are the roles of the following enzymes in catecholamine metabolism? - Catechol-O-methyltransferase (COMT) - Monoamine oxidase (MAO) - Phenylethanolamine-N-methyltransferase (PNMT)

Answer: • **COMT & MAO**: Involved in the **degradation** (breakdown) of catecholamines. • **PNMT**: Involved in the **synthesis** of epinephrine (converts Norepinephrine to Epinephrine).

Flashcard 862: Identify the clinical condition or nutrient deficiency associated with each of the following biochemical markers: - Blood protoporphyrin level - Erythrocyte glucose-6-phosphate dehydrogenase (G6PD) activity - Erythrocyte glutathione reductase activity - Erythrocyte transketolase activity - Serum methylmalonic acid level - NADPH

Answer: - **Blood protoporphyrin:** Increased in **Iron deficiency anemia** and **Lead poisoning**. - **Erythrocyte G6PD activity:** Decreased in **G6PD deficiency** (hemolytic anemia). - **Erythrocyte glutathione reductase activity:** Decreased in **Riboflavin (B2)** deficiency (FAD is a cofactor). - **Erythrocyte transketolase activity:** Decreased in **Thiamine (B1)** deficiency (TPP is a cofactor). - **Serum methylmalonic acid:** Increased in **Vitamin B12** deficiency. - **NADPH:** Derived from **Niacin (B3)**; levels reflect B3 status.

Flashcard 863: In which diseases would a deficiency of these enzymes present? - Acid α-glucosidase - Aldolase B - Fructokinase - Galactose-1-phosphate uridyl transferase - Lactase

Answer: - **Acid α-glucosidase**: Pompe disease (GSD type II) - **Aldolase B**: Hereditary fructose intolerance - **Fructokinase**: Essential fructosuria - **Galactose-1-phosphate uridyl transferase**: Classic galactosemia - **Lactase**: Lactose intolerance

Extra: - **Pompe disease**: Lysosomal acid maltase deficiency. Characterized by cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, and systemic findings leading to early death. - **Hereditary fructose intolerance**: Deficiency of Aldolase B leads to accumulation of fructose-1-phosphate; presents with hypoglycemia, jaundice, and cirrhosis after ingestion of fructose, sucrose, or sorbitol. - **Essential fructosuria**: Deficiency of fructokinase; a benign, asymptomatic condition where fructose appears in blood and urine. - **Classic galactosemia**: Deficiency of GALT. Presents with failure to thrive, jaundice, hepatomegaly, infantile cataracts, and intellectual disability. - **Lactose intolerance**: Deficiency of lactase results in osmotic diarrhea, bloating, and flatulence after dairy consumption.

Flashcard 864: 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 865: 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 866: Molecular biologists studying signal transduction apply an agent to human cells that activates G-protein-dependent phospholipase C. Which intracellular substances are most likely to increase immediately after exposure to this agent?

Answer: IP3, DAG, and Ca2+

Flashcard 867: What are the disacharide breakdown of: -Sucrose -Lactose -Maltose

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

Flashcard 868: What vitamin deficiency is commonly characterized by swollen gums, bruising, petechiae, and hemarthrosis? _____

Answer: Vitamin C deficiency (scurvy)

Flashcard 869: Which tissues are affected first in vitamin B1 (thiamine) deficiency? _____

Answer: Highly aerobic tissue (e.g. brain, heart)

Flashcard 870: Which oxygen-derived free radical is the most damaging?_____

Answer: Hydroxyl radical (·OH)