Metabolism — Flashcards

Flashcard 851: A 5 month old boy is brought to the office by his parents concerning that he has development delay. -Physical exam: unable to roll. Does not seem to recognize his parents. -Labs: Impaired tetrahydrobiopterin synthesis. -Which is most likely deficient in this patient?

Answer: Serotonin, Dopamine, and Tyrosine (BH4 is a required cofactor for tryptophan, tyrosine, and phenylalanine hydroxylases).

Flashcard 852: 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 853: 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 854: Xylulose-5-phosphate is an intermediate in which metabolic pathway?

Answer: Pentose phosphate pathway (HMP shunt)

Flashcard 855: A 5-day-old newborn presents with emesis, jaundice, lethargy, and hepatomegaly. Labs show hypoglycemia and elevated transaminases. Blood culture is positive for Gram-negative rods. Which metabolic enzyme is most likely deficient?

Answer: Galactose-1-phosphate uridyltransferase (GALT) :: Classic galactosemia; typically presents with vomiting, jaundice, hepatomegaly, cataracts, and E. coli sepsis.

Flashcard 856: what are the followings in relation to Phenylalanine metabolism? -Dihydrobiopterin reductase -Dopamine B-hydroxylase -Dopamine decarboxylase -Phenylalanine hydroxylase -Phenylethanolamine N-methyltransferase -Tyrosinase

Answer: Dihydrobiopterin reductase: convert BH2 to BH4 in order to use BH4 as a cofactor to convert phenylalanine to tyrosine. -Dopamine B-hydroxylase: convert dopamine to norepinephrine. Requires Vit. C as cofactor. -Dopamine Decarboxylase: convert DOPA to dopamine. Requires Vit. B6 as cofactor. -Phenylalanine hydroxylase: convert phenylalanine to tyrosine. Requires BH4 as cofactor. -Phenylethanolamine N-methyltransferase: convert norepinephrine to epinephrine. Requires SAM as cofactor. -Tyrosinase: convert tyrosine (DOPA to melanin). Tyrosinase deficiency will cause albinism.

Flashcard 857: What are the followings in relation to gluconeogenesis? -Glycogen phosphorylase -Hormone sensitive lipase -Lipoprotein lipase

Answer: Glycogen phosphorylase: involved in the break down of glycogen. It is the rate-limiting enzyme in glycogenolysis. Occurs during 1st several hours of fasting. 2 days will most likely be gluconeogenesis. -Hormone sensitive lipase: enzyme found in adipose tissue, will break down tryglycerides into glycerol & free fatty acids--------> leads to glucose & ketone bodies. It depends on stress hormone (catecholamines, glucagon, ACTH) -Lipoprotein lipase: enyzme found in bloodstream will break down tryglycerides found chylomicrons & VLDL and turn them to free fatty acids acids. very similar to hormone sensitive lipase.

Flashcard 858: 6 month old full term boy comes with lethargy and vomiting. -Patient was breastfed exclusively until 2 days ago when homemade purred food was added to his diet. -Serum glucose: 30 mg/dL. -Dx: confirms aldolase B deficiency. What should be removed from this patient's diet?

Answer: Sucrose or fructose due to aldolase B deficiency (sucrose: glucose+fructose) fructose --> fructose 1 phosphate by fructokinase. Fructose 1-phosphate ---> glyceraldehyde by aldolase B. Aldolase B deficiency: Fructose intolerence Fructokinase defect or deficiency: Essential fructosuria

Flashcard 859: 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 860: 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.