Metabolism — Flashcards

Flashcard 811: 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 812: 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 813: 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 814: 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 815: 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 816: 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 817: 3 day old boy comes with poor feeding, vomiting, and progressive lethargy. -Parents stated: "Diaper have burnt sugar smell" -Physical Exam: Lethargic infant with dry mucous membranes and generalized hypertonia. -Which of the following should be restricted from this infant's diet?

Answer: Leucine or VAL: Valine, Leucine, Isoleucine Due to Maple syrup urine disease, caused by a deficiency of branched chain a-ketoacid dehydrogenase thus can't metabolize VAL.

Flashcard 818: A 17 y/o boy with type 1 diabetes mellitus is found unresponsive at home. - Glucose fingerstick: 32 mg/dL - Paramedics administer an injection. - The injected substance binds to a transmembrane receptor in hepatocytes, which promotes binding of intracellular GTP to a specific receptor-associated protein. - This leads to the rapid release of glucose into the blood. Which of the following is the most likely mediator responsible for these effects? a.) cGMP dependent protein kinase b.) Janus tyrosine kinase c.) phosphodiesterase d.) Protein kinase A e.) Tyrosine specific protein kinase

Answer: d.) Protein kinase A Glucagon binds to Gs-protein coupled receptors on hepatocytes, activating adenylyl cyclase to increase cAMP levels. cAMP then activates **Protein Kinase A (PKA)**, which triggers glycogenolysis.

Flashcard 819: Which of the following reactions is a step in **gluconeogenesis**? - Acetoacetyl CoA → HMG-CoA - Acetyl CoA → Palmitic acid - Fructose 6-phosphate → Fructose 1,6-bisphosphate - Glycogen → Glucose-1-phosphate - Oxaloacetate → Phosphoenolpyruvate

Answer: Oxaloacetate → Phosphoenolpyruvate **Explanation:** - **Oxaloacetate → Phosphoenolpyruvate**: Catalyzed by PEP carboxykinase (PEPCK); a key regulatory step in **gluconeogenesis**. - **Acetoacetyl CoA → HMG-CoA**: Part of ketogenesis (mitochondria) or cholesterol synthesis (cytosol). - **Acetyl CoA → Palmitic acid**: Part of fatty acid synthesis (lipogenesis), which occurs in the well-fed state. - **Fructose 6-phosphate → Fructose 1,6-bisphosphate**: The rate-limiting step of **glycolysis** (catalyzed by PFK-1). - **Glycogen → Glucose-1-phosphate**: The process of **glycogenolysis**; liver glycogen is typically depleted after 12–24 hours of fasting.

Flashcard 820: 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.