Metabolism — Flashcards

Flashcard 801: What are the followings in relation to phosphorylation of mannose residues on glycoproteins? -Extracellular space -Lysosome -Mitochondria -Nucleus -Plasma membrane

Answer: Extracellular space: doesn't need phosphorylation of mannose residues on proteins. They will just packed in a vesicles which fuse with plasma membrane to release extracellular proteins. -Lysosome: does require phosphorylation of mannose residues on glycoproteins in order for them to enter the lysosome. Will help with degradation. -Mitochondria: They don't need protein phosphorylation. Most mitochondrial proteins will synthesize in the cytosol. -Nucleus: Protein will present with a nuclear signals (nuclear localization signals) to import or enter the nucleus. -Plasma membrane: Protein will covalently bind to an hydrophobic lipid anchor that will facilitate protein interaction with cell membrane.

Flashcard 802: What are the followings in relation to vitamin deficiency? -Abnormal oxidative decarboxylation of ketoacids. -Abnormal proline hydroxylation -Abnormal transamination -deficient methionine synthesis -Diminished synthesis of purines

Answer: Abnormal oxidative decarboxylation: Thiamine (B1) deficiency -Abnormal proline hydroxylation: vit. C deficiency -Abnormal transamination: Vit. B6 (pyridoxine) deficiency -Deficient methionine synthesis: Vit. B12 (cobalamine) deficiency. -Diminished synthesis of purines: Vit B9 (folate) deficiency

Flashcard 803: What are the followings in relation to gluconeogenesis? -Acetyl CoA -Alanine -Citrate -Fructose 2,6-bisphosphate -Lactate -Oxaloacetate

Answer: - **Acetyl-CoA**: Obligate activator of **pyruvate carboxylase**, shunting pyruvate toward gluconeogenesis. - **Alanine**: Major gluconeogenic amino acid; also **inhibits pyruvate kinase** to prevent glycolysis. - **Citrate**: **Inhibits PFK-1**, which slows glycolysis and favors gluconeogenesis. - **Fructose 2,6-bisphosphate**: Potent inhibitor of gluconeogenesis; **low levels** are necessary for gluconeogenesis to occur. - **Lactate**: Precursor produced in muscles and red blood cells; converted to glucose in the liver (**Cori cycle**). - **Oxaloacetate**: First intermediate of gluconeogenesis; must be shuttled from the mitochondria to the cytosol (via the malate shuttle) to continue the pathway.

Flashcard 804: What are the following in relation to glycogen storage diseae? -Acid maltase deficiency -Debranching enzymes -Glucose 6-phosphatase -Liver glycogen phosphorylase -Muscle glycogen phosphorylase -Pyruvate kinase

Answer: Acid maltase deficiency: (alpha 1,4 glucosidase), Pompe disease. present with cardiomegaly, hepatomegaly, hypotonia without hypoglycemia, with glycogen storage in lysosome. -Debranching enzymes: (alpha 1,6 glucosidase), Cori disease. Present with hypoglycemia, hypotonia, hepatomegaly. -Glucose 6-phosphatase: Von Gierke disease. Affect mainly liver & kidney. Hepatomegaly, lactic acidosis, hyperuricemia. -Liver glycogen phosphorylase: Hers disease. Present with hypoglycemia, ketosis, & hepatomegaly -Muscle glycogen phosphorylase deficiency: McArdle disease, presents with muscle pain & cramping during excercise, muscle get tired easily during strenuous excercise. -Pyruvate kinase: convert Phosphoenolpyruvate to pyruvate during glycolysis. Will cause chronic hemolytic anemia.

Flashcard 805: Which hormones are associated with each of the following signaling pathways? - Binding of activated receptors to DNA to modify transcription - Cyclic AMP-Protein kinase A pathway - Diacylglycerol-Protein kinase C pathway - Inositol triphosphate-calcium-calmodulin pathway - Jak-STAT pathway

Answer: - Binding of activated receptors to DNA: (Intracellular receptors) Steroids and thyroid hormones (cortisol, T3/T4, estrogen, vitamin D). - Cyclic AMP-Protein Kinase A pathway: "FLAT ChAMP GCG" (FSH, LH, ACTH, TSH, CRH, hCG, ADH-V2, MSH, PTH, Glucagon, Calcitonin, GHRH). - Diacylglycerol (DAG) & Inositol triphosphate (IP3) pathway: "GOAT HAG" (GnRH, Oxytocin, ADH-V1, TRH, Histamine-H1, Angiotensin II, Gastrin). - Jak-STAT pathway: (Receptor-associated tyrosine kinase) "PiGGLET" (Prolactin, Immunomodulators [cytokines], GH, G-CSF, Erythropoietin, Thrombopoietin).

Flashcard 806: What are the following substances? What happens due to deficiency of these substances? - Folic acid - Tocopherol - Riboflavin - Pyridoxine

Answer: - **Folic acid**: Vitamin B9; deficiency leads to megaloblastic anemia. - **Tocopherol**: Vitamin E; fat-soluble antioxidant; deficiency leads to hemolytic anemia and neurological symptoms (ataxia, loss of proprioception/vibration). - **Riboflavin**: Vitamin B2; precursor for FAD and FMN; deficiency leads to cheilosis (cracks/scaling at corners of mouth), glossitis, and corneal vascularization/keratitis. - **Pyridoxine**: Vitamin B6; deficiency leads to peripheral neuropathy, sideroblastic anemia, and homocysteinuria.

Flashcard 807: Xylulose-5-phosphate is an intermediate in which metabolic pathway?

Answer: Pentose phosphate pathway (HMP shunt)

Flashcard 808: 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 809: 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 810: 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.